Login| Sign Up| Help| Contact|

Patent Searching and Data


Title:
CELL SIGNALING GENES AND RELATED METHODS
Document Type and Number:
WIPO Patent Application WO/2006/138606
Kind Code:
A2
Abstract:
Novel plant cell signaling genes and gene products are provided. These gene, polypeptide and oligonucleotide sequences are useful in regulating plant phenotype. Moreover, these genes and gene products are useful for expression profiling of plant cell signaling genes. The invention specifically provides polynucleotide and polypeptide sequences isolated from Eucalyptus and Pinus species.

Inventors:
CHANG SHUJUN (US)
CONNETT MARIE B (AU)
EMERSON SARAH JANE (NZ)
FORSTER RICHARD L (NZ)
GAUSE KATRINA (US)
HAVUKKALA ILKKA (NZ)
HIGGINS COLLEEN (NZ)
KODRZYCKI ROBERT JOHN (US)
Application Number:
PCT/US2006/023561
Publication Date:
December 28, 2006
Filing Date:
June 16, 2006
Export Citation:
Click for automatic bibliography generation   Help
Assignee:
ARBORGEN LLC (US)
CHANG SHUJUN (US)
CONNETT MARIE B (AU)
EMERSON SARAH JANE (NZ)
FORSTER RICHARD L (NZ)
GAUSE KATRINA (US)
HAVUKKALA ILKKA (NZ)
HIGGINS COLLEEN (NZ)
KODRZYCKI ROBERT JOHN (US)
International Classes:
A01H5/00; A01H7/00; C12N5/04; C12N15/82
Foreign References:
US6867350B2
Attorney, Agent or Firm:
PEET, Richard (Washington Harbour3000 K Street, N, Washington DC, US)
Download PDF:
Claims:

1 WHAT IS CLAIMED IS:

2 1. An isolated polynucleotide comprising a nucleic acid sequence

3 selected from the group consisting of SEQ ID NOs: 1 - 197 and conservative

4 variants thereof.

5 2. The isolated polynucleotide of claim 1, wherein the β polynucleotide has a sequence comprised in a gene expressed in a wild-type

7 plant of a species of Eucalyptus or Pinus.

8 3. The isolated polynucleotide of claim 1 , wherein the variant has a g sequence identity that is greater than or equal to 99%, 98%, 97%, 96%, 95%, 0 94%, 93%, 92%, 91 %, 90%, 89%, 88%, 87%, 86%, 85%, 84%, 83%, 82%, 1 81 %, 80%, 79%, 78%, 77%, 76%, 75%, 74%, 73%, 72%, 71 %, 70%, 69%, 2 68%, 67%, 66%, 65%, 64%, 63%, 62%, 61 %, or 60% to any one of SEQ ID 3 NOs: 1 - 197.

4 4. The isolated polynucleotide of claim 1 , wherein the 5 polynucleotide encodes a protein selected from the group consisting of a 14- 6 3-3 protein, 1-aminocyclopropane-i-carboxylate synthase, 1- 7 aminocyclopropane-1-carboxylate oxidase, cyclin-dependant kinase inhibitor, s cytokinin oxidase, ethylene receptor, ethylene-responsive elongation factor 9 (EF-TS), F-box family protein, G protein-coupled receptor, GA20-oxidase, 0 giberellic acid insensitive (GAI), gibberellin 2-oxidase, indole-3-acetaldehyde 1 reductase, indole-3-acetonitrilase, Mago Nashi protein, MAP kinase, MAP 2 kinase kinase, MAP kinase kinase kinase, polyphosphoinositide binding 3 protein SSH2P, RAB11G, RAB11J, RAB5B, RAB7, RAN (GTPase activating 4 protein), RAS-like GTP-binding protein, SNF1-related protein kinase, steroid 5 reductase, steroid sulfotransferase, and synaptobrevin-like protein.

6 5. The isolated polynucleotide of claim 4, wherein the variant has a 7 sequence identity that is greater than 60%, 65%, 70%, 75%, 80%, 85% or 8 90% to any one of SEQ ID NOs: 1 - 197, and wherein the protein encoded

by the polynucleotide possesses the activity of the protein encoded by said any one of SEQ ID NOs: 1 - 197.

6. A plant cell transformed with the isolated polynucleotide of claim 1 .

7. A transgenic plant comprising the isolated polynucleotide of claim 1.

8. A DNA construct comprising at least one polynucleotide having the sequence of any one of SEQ ID NOs: 1 - 197 and conservative variants thereof.

9. The DNA construct of claim 8, further comprising a promoter, wherein the promoter and the polynucleotide are operably linked.

10. The DNA construct of claim 9, wherein the promoter is selected from the group consisting of a constitutive promoter, a strong promoter, an inducible promoter, a regulatable promoter, a temporally regulated promoter, and a tissue-preferred promoter.

11. The DNA construct of claim 8, wherein the polynucleotide encodes an RNA transcript.

12. The DNA construct of claim 11 , wherein the polynucleotide is in a sense or antisense orientation relative to the promoter.

13. The DNA construct of claim 11 , wherein the RNA transcript induces RNA interference of a polynucleotide having a nucleic acid sequence selected from the group consisting of 1 - 197.

14. A method of making a transformed plant comprising: transforming a plant cell with the DNA construct of claim 8; and culturing the transformed plant cell under conditions that promote growth of a plant.

15. A plant cell transformed with the DNA construct of claim 8.

16. A transgenic plant comprising the plant cell of claim 15.

17. The transgenic plant of claim 16, wherein a phenotype of the plant is different from a phenotype of a plant of the same species that has not been transformed with the DNA construct.

18. The transgenic plant of claim 17, wherein a phenotype that is different in the transgenic plant is selected from the group consisting of lignin quality, lignin structure, wood composition, wood appearance, wood density, wood strength, wood stiffness, cellulose polymerization, fiber dimensions, lumen size, proportion of rays, proportion of vessel elements, other plant components, plant cell division, plant cell development, number of cells per unit area, cell size, cell shape, cell wall composition, proportion of nonlignin cell wall phenolics, rate of wood formation, aesthetic appearance of wood, formation of stem defects, average microfibril angle, width of the S2 cell wall layer, rate of growth, rate of root formation ratio of root to branch vegetative development, leaf area index, and leaf shape.

19. The transgenic plant of claim 16, wherein the plant is a woody plant.

20. The transgenic plant of claim 19, wherein the plant is a tree.

21. The transgenic plant of claim 20, wherein the plant is of a species of Eucalyptus or Pinus.

22. The transgenic plant of claim 16, wherein the plant exhibits one or more traits selected from the group consisting of increased drought tolerance, herbicide resistance, reduced or increased height, reduced or increased branching, enhanced cold and frost tolerance, improved vigor, enhanced color, enhanced health and nutritional characteristics, improved storage, enhanced yield, enhanced salt tolerance, enhanced resistance of the

82 wood to decay, enhanced resistance to fungal diseases, altered

83 attractiveness to insect pests enhanced heavy metal tolerance, increased

84 disease tolerance, increased insect tolerance, increased water-stress

85 tolerance, enhanced sweetness, improved texture, decreased phosphate

86 content, increased germination, increased micronutrient uptake, improved

87 starch composition, improved flower longevity, production of novel resins,

88 increased or decreased cellulose content, increased or decreased lignin

89 content, increased or decreased nonlignin cell wall phenolics and production

90 of novel proteins or peptides, as compared to a plant of the same species that

91 has not been transformed with the DNA construct.

92 23. The transgenic plant of claim 16, wherein the plant exhibits one

93 or more traits selected from the group consisting of a reduced period of

94 juvenility, an increased period of juvenility, propensity to form reaction wood,

95 self-abscising branches, accelerated reproductive development or delayed

96 reproductive development, and accelerated regeneration, as compared to a

97 plant of the same species that has not been transformed with the DNA

98 construct.

99 24. An isolated polynucleotide comprising a nucleic acid sequence

100 encoding the catalytic or substrate-binding domain of a polypeptide selected

101 from of any one of SEQ ID NOs: 198 - 394, wherein the polynucleotide

102 encodes a polypeptide having the activity of said polypeptide selected from

103 any one of SEQ ID NOs: 198 - 394.

104 25. A method of making a transformed plant comprising:

105 transforming a plant cell with a DNA construct comprising at least one

106 polynucleotide encoding the catalytic or substrate-binding domain of a

107 polypeptide selected from of any one of SEQ ID NOs: 198 - 394; and

108 culturing the transformed plant cell under conditions that promote

109 growth of a plant.

no 26. The method of claim 25, wherein the DNA construct further in comprises a promoter, wherein the polynucleotide and the promoter are

112 operably linked.

113 27. The method of claim 25, wherein the at least one polynucleotide

114 encodes a protein that is selected from the group consisting of a 14-3-3

115 protein, i-aminocyclopropane-i-carboxylate synthase, 1-aminocyclopropane-

116 1-carboxylate oxidase, cyclin-dependant kinase inhibitor, cytokinin oxidase,

117 ethylene receptor, ethylene-responsive elongation factor (EF-TS), F-box us family protein, G protein-coupled receptor, GA20-oxidase, giberellic acid

119 insensitive (GAI), gibberellin 2-oxidase, indole-3-acetaldehyde reductase,

120 indole-3-acetonitrilase, Mago Nashi protein, MAP kinase, MAP kinase kinase,

121 MAP kinase kinase kinase, polyphosphoinositide binding protein SSH2P,

122 RAB11 G, RAB1 U, RAB5B, RAB7, RAN (GTPase activating protein), RAS-

123 like GTP-binding protein, SNF 1 -related protein kinase, steroid reductase,

124 steroid sulfotransferase, and synaptobrevin-like protein.

125 28. The method of claim 25, wherein the plant cell is located within a

126 plant explant tissue.

127 29. The method of claim 25, wherein the transgenic plant exhibits a

128 phenotype that is different from a plant of the same species that has not been

129 transformed with the DNA construct.

130 30. The method of claim 25, wherein a phenotype that is different in

131 the transgenic plant is selected from the group consisting lignin quality, lignin

132 structure, wood composition, wood appearance, wood density, wood strength,

133 wood stiffness, cellulose polymerization, fiber dimensions, lumen size,

134 proportion of rays, proportion of vessel elements, other plant components,

135 plant cell division, plant cell development, number of cells per unit area, cell

136 ' size, cell shape, cell wall composition, proportion of nonlignin cell wall

137 phenolics, rate of wood formation, aesthetic appearance of wood, formation of

138 stem defects, average microfibril angle, width of the S2 cell wall layer, rate of

139 growth, rate of root formation ratio of root to branch vegetative development,

140 leaf area index, and leaf shape.

141 31. The method of claim 25, wherein the transgenic plant exhibits

142 one or more traits selected from the group consisting of increased drought

143 tolerance, herbicide resistance, reduced or increased height, reduced or

144 increased branching, enhanced cold and frost tolerance, improved vigor,

145 enhanced color, enhanced health and nutritional characteristics, improved

146 storage, enhanced yield, enhanced salt tolerance, enhanced resistance of the

147 wood to decay, enhanced resistance to fungal diseases, altered

148 attractiveness to insect pests enhanced heavy metal tolerance, increased

149 disease tolerance, increased insect tolerance, increased water-stress

150 tolerance, enhanced sweetness, improved texture, decreased phosphate

151 content, increased germination, increased micronutrient uptake, improved

152 starch composition, improved flower longevity, production of novel resins,

153 increased or decreased cellulose content, increased or decreased lignin

154 content, increased or decreased nonlignin cell wall phenolics and production

155 of novel proteins or peptides, as compared to a plant of the same species that

156 has not been transformed with the DNA construct.

157 32. Wood obtained from a transgenic tree which has been

158 transformed with the DNA construct of claim 8.

159 33. Wood pulp obtained from a transgenic tree which has been

160 transformed with the DNA construct of claim 8.

161 34. The wood pulp of claim 33, wherein the DNA construct

162 comprises a nucleotide sequence encoding a polypeptide comprising the

163 amino acid sequence of any one of SEQ ID NOs: 198 - 394.

164 35. A method of making wood, comprising:

165 transforming a plant with a DNA construct comprising a polynucleotide

166 having a nucleic acid sequence selected from the group consisting of SEQ ID

167 NOs: 1 - 197 and conservative variants thereof;

168 culturing the transformed plant under conditions that promote growth of

169 a plant; and

170 obtaining wood from the plant.

171 36. A method of making wood pulp, comprising:

172 transforming a plant with a DNA construct comprising a polynucleotide

173 having a nucleic acid sequence selected from the group consisting of SEQ ID

174 NOs: 1 - 197 and conservative variants thereof;

175 culturing the transformed plant under conditions that promote growth of

176 a plant; and

177 obtaining wood pulp from the plant.

178 37. An isolated polypeptide comprising an amino acid sequence

179 encoded by the isolated polynucleotide of claim 1.

180 38. An isolated polypeptide comprising an amino acid sequence

181 selected from the group consisting of SEQ ID NOs: 198 - 394.

182 39. A method of altering a plant phenotype of a plant, comprising

183 altering expression in the plant of a polypeptide encoded by any one of SEQ

184 ID NOs: 1 - 197.

185 40. The method of claim 39, wherein the expression is up-regulated,

186 down-regulated, silenced, or developmentally regulated.

187 41. The method of claim 39, wherein the plant phenotype is selected

188 from the group consisting of lignin quality, lignin structure, wood composition,

189 wood appearance, wood density, wood strength, wood stiffness, cellulose

190 polymerization, fiber dimensions, lumen size, proportion of rays, proportion of

191 vessel elements, other plant components, plant cell division, plant cell

192 development, number of cells per unit area, cell size, cell shape, cell wall

193 composition, proportion of nonlignin cell wall phenolics, rate of wood

194 formation, aesthetic appearance of wood, formation of stem defects, average

195 microfibril angle, width of the S2 cell wall layer, rate of growth, rate of root

196 formation ratio of root to branch vegetative development, leaf area index, and

197 leaf shape.

198 42. The method of claim 39, wherein the plant exhibits one or more

199 traits selected from the group consisting of increased drought tolerance,

200 herbicide resistance, reduced or increased height, reduced or increased

201 branching, enhanced cold and frost tolerance, improved vigor, enhanced

202 color, enhanced health and nutritional characteristics, improved storage,

203 enhanced yield, enhanced salt tolerance, enhanced resistance of the wood to

204 decay, enhanced resistance to fungal diseases, altered attractiveness to

205 insect pests enhanced heavy metal tolerance, increased disease tolerance,

206 increased insect tolerance, increased water-stress tolerance, enhanced

207 sweetness, improved texture, decreased phosphate content, increased

208 germination, increased micronutrient uptake, improved starch composition,

209 improved flower longevity, production of novel resins, increased or decreased

210 cellulose content, increased or decreased lignin content, increased or

211 decreased nonlignin cell wall phenolics and production of novel proteins or

212 peptides, as compared to a plant of the same species that has not been

213 transformed with the DNA construct.

214 43. A polynucleotide comprising a nucleic acid selected from the

215 group comprising of SEQ ID NOs: 395 - 583.

216 44. The polynucleotide of claim 43, wherein said polynucleotide is

217 comprised of less than about 100 nucleotide bases.

218 45. A method of correlating gene expression in two different

219 samples, comprising:

220 detecting a level of expression of one or more genes encoding a

221 product encoded by a nucleic acid sequence selected from the group

222 consisting of SEQ ID NOs: 1 - 197 and conservative variants thereof in a first

223 sample;

224 detecting a level of expression of the one or more genes in a second

225 sample;

226 comparing the level of expression of the one or more genes in the first

227 sample to the level of expression of the one or more genes in the second

228 sample; and

229 correlating a difference in expression level of the one or more genes

230 between the first and second samples.

231 46. The method of claim 45, wherein the first sample and the

232 second sample are each from a different type of plant tissue.

233 47. The method of claim 45, wherein the first sample and the

234 second sample are from the same tissue, and wherein the first sample and

235 the second sample are each harvested during a different season of the year.

236 48. The method of 45, wherein the first sample and the second

237 sample are obtained from plants in different stages of development.

238 49. The method of claim 45, wherein the first sample is obtained

239 from a plant not exposed to an environmental stimulus, and wherein the

240 second samples is obtained from a plant exposed to an environmental

241 stimulus.

242 50. The method of claim 49, wherein the environmental stimulus is

243 selected from the group consisting of change in temperature, change in

244 amount of light, change in availability of water, change in availability of

245 nutrients, change in availability of atmospheric gases, frost, wounding from

246 mechanical injury, and wounding from attack by an insect, fungus, bacteria or

247 virus.

248 51. A method of correlating the possession of a plant phenotype to

249 the level of gene expression in the plant of one or more genes comprising:

250 detecting a level of expression of one or more genes encoding a

251 product encoded by a nucleic acid sequence selected from the group

252 consisting of SEQ ID NOs: 1 - 197 and conservative variants thereof in a first

253 plant possessing a phenotype;

254 detecting a level of expression of the one or more genes in a second

255 plant lacking the phenotype;

256 comparing the level of expression of the one or more genes in the first

257 plant to the level of expression of the one or more genes in the second plant;

258 and

259 correlating a difference in expression level of the one or more genes

260 between the first and second plants to possession of the phenotype.

261 52. A method of correlating gene expression to a response to an

262 external stimulus or environmental condition, comprising:

263 detecting a level of expression of one or more genes encoding a

264 product encoded by a nucleic acid sequence selected from the group

265 consisting of SEQ ID NOs: 1 - 197 and conservative variants thereof in a first

266 plant cell in the absence of the external stimulus or environmental condition;

267 detecting a level of expression of the one or more genes in a second

268 plant cell in the presence of the external stimulus or environmental condition;

269 comparing the level of the expression of the one or more genes in the

270 first plant cells to the level of expression of the one or more genes in the

271 second plants cells; and

272 correlating a difference in expression level of the one or more genes

273 between the first and second samples to presence of the external stimulus or

274 environmental condition.

275 53. The method of claim 45 wherein the first and second samples

276 are both obtained from a plant tissue selected from the group consisting of

277 vascular tissue, apical meristem, vascular cambium, xylem, phloem, root,

278 flower, cone, fruit, and seed.

279 54. The method of claim 53, wherein the plant tissue of the first

280 sample and second samples are each obtained from a different type of

281 tissues.

282 55. The method of claim 53, wherein the first and second samples

283 are each obtained from a plant tissue in a different stage of development.

284 56. The method of claim 52 wherein the external stimulus is

285 selected from the group consisting of change in temperature, change in

286 amount of light, change in availability of water, change in availability of

287 nutrients, wounding from mechanical injury, and wounding from attack by

288 pathogens.

289 57. The method of any one of claims 51 or 52, wherein the first and

290 second plants or plant cells are of a species selected from Eucalyptus and

291 Pinus species.

292 58. The method of any one of claims 51 or 52, wherein the first and

293 second plants or plant cells are of a species selected from Eucalyptus grandis

294 or Pinus radiata.

295 59. The method of any one of claims 45, 51 or 52, wherein the step

296 of detecting is effected using one or more polynucleotides capable of

297 hybridizing to a nucleic acid sequence selected from the group consisting of

298 SEQ ID NOs: 1 - 197 under standard hybridization conditions.

299 60. The method of any one of claims 45, 51 or 52, wherein the step

300 of detecting is effected using one or more polynucleotides capable of

301 hybridizing to a nucleic acid sequence encoded by a nucleic acid sequence

302 selected from the group consisting of SEQ ID NOs: 1 - 197 under standard

303 hybridization conditions.

304 61. The method of any one of claims 45, 51 or 52,, wherein the step

305 of detecting is effected by hybridization to a labeled nucleic acid.

306 62. The method of claim 59, wherein the one or more

307 polynucleotides are labeled with a detectable label.

308 63. The method of claim 59, wherein at least one of the one or more

309 polynucleotides hybridizes to a 3' untranslated region of one of the one or

310 more genes.

311 64. The method of claim 60, wherein at least one of the one or more

312 polynucleotides hybridizes to the 3' untranslated region of one of the one or

313 more genes.

314 65. The method of claim 59, wherein the one or more

315 polynucleotides comprises a nucleic acid sequence selected from the group

316 consisting of SEQ ID NOs: 395 - 583.

317 66. The method of claim 60, wherein the one or more

318 polynucleotides comprises a nucleic acid sequence selected from the group

319 consisting of SEQ ID NOs: 395 - 583.

320 67. The method of claim 59, wherein the one or more

321 polynucleotides is selected from the group consisting of DNA or RNA.

322 68. The method of claim 60, wherein the one or more

323 polynucleotides is selected from the group consisting of DNA or RNA.

324 69. The method of any one of claims 45, 51 or 52, further

325 comprising, prior to the detecting steps, the step of amplifying the one or more

326 genes in the first and second plant or plant cells.

327 70. The method according to any one of claims 45, 51 or 52, further

328 comprising, prior to the detecting steps, the step of labeling the one or more

329 genes in the first and second plant or plant cells with a detectable label.

330 71. A combination for detecting expression of one or more genes,

331 comprising two or more oligonucleotides, wherein each oligonucleotide is

332 capable of hybridizing to a nucleic acid sequence selected from the group

333 consisting of SEQ ID NOs: 1 - 197.

334 72. A combination for detecting expression of one or more genes,

335 comprising two or more oligonucleotides, wherein each oligonucleotide is

336 capable of hybridizing to a nucleic acid sequence encoded by a nucleic acid

337 sequence selected from the group consisting of SEQ ID NOs: 1 - 197.

338 73. The combination of claim 71 , wherein each of the two or more

339 oligonucleotides hybridizes to a different one of the nucleic acid sequences

340 selected from the group consisting of SEQ ID NOs: 1 - 197.

341 74. The combination of claim 72, wherein each of the two or more

342 oligonucleotides hybridizes to a nucleotide sequence encoded by a different

343 one of the nucleic acid sequences selected from the group consisting of SEQ

344 ID NOs: 1 - 197.

345 75. The combination of claim 71 , wherein at least one of the two or

346 more oligonucleotides hybridizes to a 3' untranslated region of a nucleic acid

347 sequence selected from the group consisting of SEQ ID NOs: 1 - 197.

348 76. The combination of claim 72, wherein at least one of the two or

349 more oligonucleotides hybridizes to nucleic acid sequence that is

350 complementary to a 3' untranslated region of a nucleic acid sequence

351 selected from the group consisting of SEQ ID NOs: 1 - 197.

352 77. The combination of any one of claims 71 or 72, wherein each of

353 the two or more oligonucleotides are comprised of fewer than about 100

354 nucleotide bases.

355 78. The combination of claim 71 , wherein at least one of the two or

356 more oligonucleotides comprises a nucleic acid sequence selected from the

357 group consisting of SEQ ID NOs: 395 - 583.

358 79. The combination of claim 72, wherein at least one of the two or

359 more oligonucleotides comprises a nucleic acid sequence selected from the

360 group consisting of SEQ ID NOs 395 - 583.

361 80. The combination of claim 71 , wherein each of the two or more

362 oligonucleotides hybridizes to a gene encoding a protein selected from the

363 group consisting of a 14-3-3 protein, i-aminocyclopropane-i-carboxylate

364 synthase, 1-aminocyclopropane-i-carboxylate oxidase, cyclin-dependant

365 kinase inhibitor, cytokinin oxidase, ethylene receptor, ethylene-responsive

366 elongation factor (EF-TS), F-box family protein, G protein-coupled receptor,

367 GA20-oxidase, giberellic acid insensitive (GAI), gibberellin 2-oxidase, indole-

368 3-acetaldehyde reductase, indole-3-acetonitrilase, Mago Nashi protein, MAP

369 kinase, MAP kinase kinase, MAP kinase kinase kinase, polyphosphoinositide

370 binding protein SSH2P, RAB11G, RAB11J, RAB5B, RAB7, RAN (GTPase

371 activating protein), RAS-like GTP-binding protein, SNF1 -related protein

372 kinase, steroid reductase, steroid sulfotransferase, and synaptobrevin-like

373 protein.

374 81. The combination of claim 72, wherein each of the two or more

375 oligonucleotides hybridizes to a nucleic acid sequence encoded by a gene

376 encoding a protein selected from the group consisting of a 14-3-3 protein, 1-

377 aminocyclopropane-1-carboxylate synthase, 1-aminocyclopropane-1-

378 carboxylate oxidase, cyclin-dependant kinase inhibitor, cytokinin oxidase,

379 ethylene receptor, ethylene-responsive elongation factor (EF-TS), F-box

380 family protein, G protein-coupled receptor, GA20-oxidase, giberellic acid

381 insensitive (GAI), gibberellin 2-oxidase, indole-3-acetaldehyde reductase,

382 indole-3-acetonitrilase, Mago Nashi protein, MAP kinase, MAP kinase kinase,

383 MAP kinase kinase kinase, polyphosphoinositide binding protein SSH2P,

384 RAB11 G, RAB11J, RAB5B, RAB7, RAN (GTPase activating protein), RAS-

385 like GTP-binding protein, SNF1 -related protein kinase, steroid reductase,

386 steroid sulfotransferase, and synaptobrevin-like protein.

387 82. The combination of claim 80, wherein each of the two or more

388 oligonucleotides hybridizes to a gene encoding a different one of the proteins.

389 83. The combination of claim 81 , wherein each of the two or more

390 oligonucleotides hybridizes to a nucleic acid sequence encoded by a gene

391 encoding a different one of the proteins.

392 84. The combination of claim 80, wherein each of the two or more

393 oligonucleotides hybridizes to a different gene.

394 85. The combination of claim 81 , wherein each of the two or more

395 oligonucleotides hybridizes to a nucleic acid sequence encoded by a different

396 gene.

397 86. The combination of any one of claims 71 or 72, comprising from

398 about 2 to about 5000 of the two or more oligonucleotides.

399 87. The combination of any one of claims 71 or 72, wherein each of

400 the two or more oligonucleotides is labeled with a detectable label.

401 88. A microarray comprising the combination of any one of claims

402 71-87 provided on a solid support, wherein each of said two or more

403 oligonucleotides occupies a unique location on said solid support.

404 89. A method for detecting one or more genes in a sample

405 comprising:

406 contacting the sample with two or more oligonucleotides, wherein each

407 oligonucleotide is capable of hybridizing to a gene comprising a nucleic acid

408 sequence selected from the group consisting of SEQ ID NOs: 1 - 197 under

409 standard hybridization conditions; and

410 detecting the one or more genes of interest which are hybridized to the

411 one or more oligonucleotides.

412 90. A method for detecting one or more nucleic acid sequences

413 encoded by one or more genes in a sample, comprising:

414 contacting the sample with two or more oligonucleotides,

415 wherein each oligonucleotide is capable of hybridizing to a nucleic acid

416 sequence encoded by a gene comprising a nucleic acid sequence selected

417 from the group consisting of SEQ ID NOs: 1 - 197 under standard

418 hybridization conditions; and

419 detecting the one or more nucleic acid sequences which are

420 hybridized to the one or more oligonucleotides.

421 91. The method of claim 89, wherein each of the two or more

422 oligonucleotides hybridizes to a gene comprising a different one of the nucleic

423 acid sequences selected from the group consisting of SEQ ID NOs: 1 - 197.

424 92. The method of claim 90, wherein each of the two or more

425 oligonucleotides hybridizes to a nucleic acid sequence encoded by a gene

426 comprising a different one of the nucleic acid sequences selected from the

427 group consisting of SEQ ID NOs: 1 - 197.

428 93. The method of claim 89, wherein at least one of the two or more

429 oligonucleotides hybridizes to a 3' untranslated region of a gene comprising a

430 nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1 -

431 197.

432 94. The method of claim 90, wherein at least one of the two or more

433 oligonucleotides hybridizes to a nucleic acid sequence that is complementary

434 to a 3' untranslated region of a gene comprising a nucleic acid sequence

435 selected from the group consisting of SEQ ID NOs: 1 - 197.

436 95. The method of any one of claims 89 or 90, wherein each of the

437 two or more oligonucleotides are comprised of fewer than about 100

438 nucleotide bases.

439 96. The method of claim 89, wherein at least one of the two or more

440 oligonucleotides comprises a nucleic acid sequence selected from the group

441 consisting of SEQ ID NOs 395 - 583.

442 97. The method of claim 90, wherein at least one of the two or more

443 oligonucleotides comprises a nucleic acid sequence selected from the group

444 consisting of SEQ ID NOs 395 - 583.

445 98. The method of claim 89, wherein each of the two or more

446 oligonucleotides hybridizes to a gene encoding a protein selected from the

447 group consisting of a 14-3-3 protein, 1-aminocyclopropane-i-carboxylate

448 synthase, 1-aminocyclopropane-i-carboxylate oxidase, cyclin-dependant

449 kinase inhibitor, cytokinin oxidase, ethylene receptor, ethylene-responsive

450 elongation factor (EF-TS), F-box family protein, G protein-coupled receptor,

451 GA20-oxidase, giberellic acid insensitive (GAI), gibberellin 2-oxidase, indole-

452 3-acetaldehyde reductase, indole-3-acetonitrilase, Mago Nashi protein, MAP

453 kinase, MAP kinase kinase, MAP kinase kinase kinase, polyphosphoinositide

454 binding protein SSH2P, RAB11 G, RAB11J, RAB5B, RAB7, RAN (GTPase

455 activating protein), RAS-like GTP-binding protein, SNF1 -related protein

456 kinase, steroid reductase, steroid sulfotransferase, and synaptobrevin-like

457 protein.

458 99. The method of claim 90, wherein each of the two or more

459 oligonucleotides hybridizes to a nucleic acid sequence encoded by a gene

460 encoding a protein selected from the group consisting of a 14-3-3 protein, 1-

461 aminocyclopropane-1-carboxylate synthase, 1-aminocyclopropane-1-

462 carboxylate oxidase, cyclin-dependant kinase inhibitor, cytokinin oxidase,

463 ethylene receptor, ethylene-responsive elongation factor (EF-TS), F-box

464 family protein, G protein-coupled receptor, GA20-oxidase, giberellic acid

465 insensitive (GAI), gibberellin 2-oxidase, indole-3-acetaldehyde reductase,

466 indole-3-acetonitrilase, Mago Nashi protein, MAP kinase, MAP kinase kinase,

467 MAP kinase kinase kinase, polyphosphoinositide binding protein SSH2P,

468 RAB11G, RAB11 J, RAB5B, RAB7, RAN (GTPase activating protein), RAS-

469 like GTP-binding protein, SNF1 -related protein kinase, steroid reductase,

470 steroid sulfotransferase, and synaptobrevin-like protein.

471 100. The method of claim 98, wherein each of the two or more

472 oligonucleotides hybridizes to a gene encoding a different one of the proteins.

473 101. The method of claim 99, wherein each of the two or more

474 oligonucleotides hybridizes to a nucleic acid sequence encoded by a gene

475 encoding a different one of the proteins.

476 102. The method of any one of claims 89 or 90, wherein the two or

477 more oligonucleotides are provided on a solid support, wherein each of the

478 two of more oligonucleotides occupy a unique location on the solid support.

479 103. The method of claim 102, wherein the solid support comprises

480 from about 2 to about 5000 of the two or more oligonucleotides.

481 104. The method of any one of claims 89 or 90, further comprising,

482 prior to the contacting step, the step of amplifying the one or more genes or

483 nucleic acid sequences in the sample.

484 105. The method of any one of claims 89 or 90, further comprising,

485 prior to the contacting step, the step of labeling the one or more genes or

486 nucleic acid sequences in the sample with a detectable label.

487 106. A kit for detecting gene expression comprising the microarray of

488 claim 88 together with one or more buffers or reagents for a nucleotide

489 hybridization reaction.

490

Description:

Cell Signaling Genes and Related Methods

BACKGROUND

FIELD OF THE INVENTION

[001] The present invention relates generally to the field of plant cell signaling genes and polypeptides encoded by such genes, and the use of such polynucleotide and polypeptide sequences for controlling plant phenotype. The invention specifically provides cell signaling polynucleotide and polypeptide sequences isolated from Eucalyptus and Pinus and sequences related thereto.

BACKGROUND

A. Cell Signaling Genes and Gene Products

[002] Plants progress through set developmental programs throughout the course of their lifetimes. This is particularly evident in embryogenesis and floral development. There are a variety of signal molecules produced by certain cells in the plant to which other cells, particularly in the meristematic regions, are poised to respond. These signal molecules trigger distinct sets of developmental programs at specific times that lead to the formation of, for example, flowers or cotyledons. In addition to the programmed developmental pathways, plants are exposed to a variety of environmental stimuli such as changes in temperature and amount of sunlight, availability of water, wounding from mechanical injury and attack by pathogens. Environmental factors, such as exposure to light, heat, cold, drought, etc., activate the expression of genes and synthesis of proteins and other compounds essential for an appropriate response to the environmental signal and thereby, the healthy development of the plant. These responses, like the developmental pathways, are mediated by signal molecules.

[003] To respond to these signal molecules, plant cells produce surface receptor proteins that serve as sensors, regulators and/or transducers of cell signals. The intracellular transduction of a signal is often transmitted via a phosphorylation cascade of molecules that culminates in the transcription of genes to elicit the appropriate cellular response either for normal development or against environmental challenge.

[004] One major class of receptor proteins is the single-transmembrane family, of which there are several subclasses. These proteins are characterized by three domains: an extracellular signal molecule (or ligand) recognition/binding domain, a single cell membrane-spanning domain and an intracellular signal transduction domain which is usually a protein kinase. Many, but not all, plant single transmembrane proteins belong to the subclass known as receptor-like kinases (RLKs). The intracellular kinase domains of plant RLKs are all serine/threonine protein kinases, while the extracellular domains of RLKs are of different types. One type of RLK is characterized by the presence of the extracellular S-domain, originally described in self- incompatibility-locus glycoproteins that inhibit self-pollination. The S-domain is recognized by an array of ten cysteine residues in combination with other conserved residues. Another class of RLKs has an extracellular domain distinguished by leucine rich repeats (LRR) that are involved in protein-protein interactions. Binding of ligands to the extracellular domain is followed by receptor dimerization, autophosphorylation and the activation of a series of intracellular proteins which serve to transduce the signal to the nucleus. The structure of plant RLKs is very similar to receptors found in cell signaling pathways in animal systems.

[005] One example of a plant RLK is the Xa21 gene, which confers resistance to the plant pathogen Xanthomonas oryzae pv. oryzae race 6. This gene was cloned using genetic means comparing Xanthomonas-sensitive and resistant strains of rice (Song et al., Science 270:1804-1806 (1995)), and has been subsequently been shown to confer resistance to Xanthomonas in Arabidopsis. The 1025 amino acid protein possesses a number of features

with similarity to known protein domains including a NH 2 -terminal 23 amino acid residue signal peptide, indicating that the protein is directed to the plasma membrane. Amino acids 81 to 634 contain 23 imperfect copies of a 24-amino acid LRR. Amino acids 651 to 676 encode a 26-amino acid hydrophobic segment that is likely to form a membrane-spanning domain. The C-terminal amino acids contain a putative intracellular serine threonine kinase domain carrying 11 subdomains with all 15 invariant amino acids that are typical of protein kinases. Subdomains Vl and VIII are indicative of serine- threonine phosphorylation specificity. Xa21 has strong similarities to other RLKs, such as the Arabidopsis receptor-like kinase proteins RLK5 and TMK1 , showing conservation of both the LRR and protein kinase domains. It is not yet known to what protein Xa21 transduces its pathogen recognition signal. [006] Another kind of membrane receptor molecule expressed by plant cells is histidine kinases (HKs). HKs have been known for some time in bacterial signal transduction systems, where they form one half of a two-component signaling system. The bacterial HK serves as a sensor molecule for extracellular signals, such as changes in osmoticum, nutrients and toxins. The HK autophosphorylates on a histidine residue in response to ligand binding. This phosphohistidine donates its phosphate group to an aspartate residue of the second member of the two component system, known as the response regulator (RR). The phosphorylated RR then binds DNA in a sequence- specific manner, serving to directly activate specific genes which code for proteins that mediate the response to the extracellular stimulus. [007] Like bacteria, plant cells have a two-component signaling system which consists of a sensor element HK and a RR. The two components may be separate molecules or may exist as a hybrid molecule (hereinafter referred to as hybrid HK/RR proteins). The HK proteins are distinguished by well- conserved amino acid motifs that occur in a specific order. From the amino terminus, the conserved regions are identified as the H, N, G1 , F and G2 boxes. These motifs are usually found within a 200-250 amino acid span of the protein. The G1 , F and G2 boxes are thought to be involved in nucleotide

binding. As in bacteria, upon receiving the extracellular signal, the HK is autophosphorylated on the histidine residue contained in the H box. The phosphate group is subsequently transferred to the RR. All HKs are believed to phosphorylate a RR, as an obligate part of signal transduction. RRs are characterized by the absolute conservation of an aspartate which is phosphorylated by the phosphohistidine of the HK, and a conserved lysine residue. Unlike bacteria, RRs in plants have not been shown to bind DNA directly. Rather, the plant RRs characterized to date appear to transduce the signal into protein kinase cascades, which eventually phosphorylate and activate or inactivate transcription factors, and thereby affect gene expression. [008] The ethylene receptor (ETR1 ; Chang et al. Science 262:539-544) is the best known two-component signaling system in plants. Ethylene is a well known signal molecule that is involved in the regulation of plant development as well as the coordination of fertilization, senescence, skoto/ photomorphogenesis and responses to pathogens and mechanical injury. The ethylene receptor is a hybrid HK/RR protein. The signal is transduced through a Raf-like protein kinase named CTRL CTR1 is a negative regulator of downstream steps in the signaling pathway. While the details of this pathway remain unclear, it appears that the HK is constitutively active in the absence of ethylene, thereby constantly phosphorylating CTR1 , which in turn represses other genes in the ethylene response pathway. Binding of ethylene to ETR1 inhibits the HK function of the receptor, resulting in the inhibition of the negative regulator CTR1 , thereby allowing the activation of downstream proteins in the ethylene signal transduction cascade. This culminates in activation of ethylene response genes.

[009] More recently, two RR genes, IBC6 and IBC7, which are induced in response to the plant growth regulator cytokinin, have been cloned from Arabidopsis thaliana and characterized (Brandstatter and Kieber, The Plant Cell 70:1009-1019 (1998)). It is likely that IBC6 and IBC7 are involved in the transduction of the cytokinin signal in plants. This is particularly interesting in light of the fact that a gene encoding the hybrid HK/RR protein CKH

(Kakimoto, Science 274:982-985, 1996) causes cytokinin-like effects when it is ectopically expressed in transgenic plants. Thus it appears likely that a two-component HK/RR system is involved in cytokinin signal transduction. Cytokinin is known to regulate plant growth and development, including such physiological events as nutrient metabolism, expansion and senescence of leaves, and lateral branching.

[010] While polynucleotides encoding proteins involved in plant cell signaling have been isolated for certain species of plants, genes encoding many such proteins have not yet been identified in a wide range of plant species. Thus, there remains a need in the art for materials which may be usefully employed in the modification of cell signaling in plants.

[011] Proper plant growth and development requires the ability to react to environmental and developmental factors. Throughout its life, a plant is subject to changes in light, temperature, water and nutrient availability. Plants are also subject to attack by pathogens, such as viruses, nematodes, mites, and insects. Reacting to developmental and environmental cues requires complex interactions between environmental signals and factors internal to the plant. Such reaction is typically effected by changes in gene expression. Various internal signals are required for coordinating gene expression during development and in response to environmental factors. These internal signals are communicated throughout by signal transduction pathways that allow propagation of the original signal. This ultimately results in the activation or suppression of gene expression.

[012] Plant development is also affected by cell environmental factors such as temperature, nutrient availability, light, etc. See Gastal and Nelon, Plant Physiol. 705:191-7 (1994), Ben-Haj-Sahal and Tardieu, Plant Physiol. 709:861-7 (1995), and Sacks et al., Plant Physiol. 114:519-27 (1997). Plant development and phenotype are affected by cell signaling, and altering expression of the genes involved in the cell signaling can be a useful method of modifying plant development and altering plant phenotype.

[013] The ability to alter expression of cell signaling genes is extremely powerful because cell signaling drives plant development, including growth rates, responses to environmental cues, and resulting plant phenotype. Control of plant cell signaling and phenotypes associated with alteration of cell signaling gene expression has, among others, applications for alteration of wood properties and, in particular, lumber and wood pulp properties. For example, improvements to wood pulp that can be effected by altering cell signaling gene expression include increased or decreased lignin content, increased accessibility of lignin to chemical treatments, improved reactivity of lignin, and increased or decreased cellulose or hemi content. Manipulating the plant signal transduction pathways can also engineer better lumber having increased dimensional stability, increased tensile strength, increased shear strength, increased compression strength, increased shock resistance, increased stiffness, increased or decreased hardness, decreased spirality, decreased shrinkage, and desirable characteristics with respect to weight, density, and specific gravity.

B. Expression Profiling and Microarray Analysis in Plants [014] The multigenic control of plant phenotype presents difficulties in determining the genes responsible for phenotypic determination. One major obstacle to identifying genes and gene expression differences that contribute to phenotype in plants is the difficulty with which the expression of more than a handful of genes can be studied concurrently. Another difficulty in identifying and understanding gene expression and the interrelationship of the genes that contribute to plant phenotype is the high degree of sensitivity to the environmental factors that plants demonstrate.

[015] There have been recent advances using genome-wide expression profiling. In particular, the use of DNA microarrays has been useful to examine the expression of a large number of genes in a single experiment. Several studies of plant gene responses to developmental and environmental stimuli have been conducted using expression profiling. For example, microarray analysis was employed to study gene expression during fruit

ripening in strawberry, Aharoni et al., Plant Physiol. 129λ' 019-1031 (2002), wound response in Arabidopsis, Cheong et al., Plant Physiol. -/29:661-7 (2002), pathogen response in Arabidopsis, Schenk et al., Proc. Nat'l Acad. Sci. 97:11655-60 (2000), and auxin response in soybean, Thibaud-Nissen et al., Plant Physiol. 132:M8. Whetten et al., Plant MoI. Biol. 47:275-91 (2001) discloses expression profiling of cell wall biosynthetic genes in Pinus taeda L using cDNA probes. Whetten et al. examined genes which were differentially expressed between differentiating juvenile and mature secondary xylem. Additionally, to determine the effect of certain environmental stimuli on gene expression, gene expression in compression wood was compared to normal wood. 156 of the 2300 elements examined showed differential expression. Whetten, supra at 285. Comparison of juvenile wood to mature wood showed 188 elements as differentially expressed. Id. at 286.

[016] Although expression profiling and, in particular, DNA microarrays provide a convenient tool for genome-wide expression analysis, their use has been limited to organisms for which the complete genome sequence or a large cDNA collection is available. See Hertzberg et al., Proc. Nat'l Acad. Sci. 98:14732-7 (2001a), Hertzberg et al., Plant J. 25:585 (2001b). For example, Whetten, supra, states, "A more complete analysis of this interesting question awaits the completion of a larger set of both pine and poplar ESTs." Whetten et al. at 286. Furthermore, microarrays comprising cDNA or EST probes may not be able to distinguish genes of the same family because of sequence similarities among the genes. That is, cDNAs or ESTs, when used as microarray probes, may bind to more than one gene of the same family. [017] Methods of manipulating gene expression to yield a plant with a more desirable phenotype would be facilitated by a better understanding of cell signaling gene expression in various types of plant tissue, at different stages of plant development, and upon stimulation by different environmental cues. The ability to control plant architecture and agronomically important traits would be improved by a better understanding of how cell signaling gene expression effects formation of plant tissues, how cell signaling gene

expression protects plants from pathogens and adverse environmental conditions, and how plant growth and the cell signaling are connected. Among the large number of genes, the expression of which can change during development of a plant, only a fraction are likely to effect phenotypic changes of agronomic significance.

SUMMARY

[018] Accordingly, there is a need for tools and methods useful in determining the changes in the expression of cell signaling genes that result in desirable plant phenotypes. There is also a need for polynucleotides useful in such methods. There is a further need for methods which can correlate changes in cell signaling gene expression to a phenotype. There is a further need for methods of identifying cell signaling genes and gene products that impact plant phenotype and that can be manipulated to obtain a desired phenotype.

[019] In one embodiment, an isolated polynucleotide is provided comprising a nucleic acid sequence selected from the group consisting of SEQ ID NO: 1- 197 or a conservative variant thereof. In one aspect, the polynucleotide has a sequence comprised in a gene expressed in a wild-type plant of a species of Eucalyptus or Pinus. In another aspect, the variant has a sequence identity that is greater than or equal to 99%, 98%, 97%, 96%, 95%, 94%, 93%, 92%, 91%, 90%, 89%, 88%, 87%, 86%, 85%, 84%, 83%, 82%, 81%, 80%, 79%, 78%, 77%, 76%, 75%, 74%, 73%, 72%, 71 %, 70%, 69%, 68%, 67%, 66%, 65%, 64%, 63%, 62%, 61%, or 60%, to any one of SEQ ID NO: 1-197. [020] In one aspect, the polynucleotide encodes a protein such as a 14-3-3 protein, 1-aminocyclopropane-i-carboxylate synthase, 1-aminocyclopropane- 1-carboxylate oxidase, cyclin-dependant kinase inhibitor, cytokinin oxidase, ethylene receptor, ethylene-responsive elongation factor (EF-TS), F-box family protein, G protein-coupled receptor, GA20-oxidase, giberellic acid insensitive (GAI), gibberellin 2-oxidase, indole-3-acetaldehyde reductase, indole-3-acetonitrilase, Mago Nashi protein, MAP kinase, MAP kinase kinase,

MAP kinase kinase kinase, polyphosphoinositide binding protein SSH2P, RAB11G, RAB11J, RAB5B, RAB7, RAN (GTPase activating protein), RAS- like GTP-binding protein, SNF1 -related protein kinase, steroid reductase, steroid sulfotransferase, synaptobrevin-like protein or a catalytic domain thereof, or a protein having the same function. In another aspect, the polynucleotide comprises a variant having a sequence identity that is greater than 60%, 65%, 70%, 75%, 80%, 85% or 90% to any one of SEQ ID NO: 1- 197 and the protein encoded by the polynucleotide possesses the activity of the protein encoded by the SEQ ID NO: 198-394.

[021] In one embodiment, a plant cell is provided which is transformed with an isolated polynucleotide of SEQ ID NO: 1-197. In another embodiment, a transgenic plant is provided comprising an isolated polynucleotide of SEQ ID NO: 1-197.

[022] In one embodiment, a DNA construct is provided comprising at least one polynucleotide having the sequence of any one of SEQ ID NO: 1-197 or a conservative variants thereof. In one aspect, the DNA construct comprises a promoter operably linked to the polynucleotide. In another aspect, the promoter is selected from any one of a constitutive promoter, a strong promoter, an inducible promoter, a regulatable promoter, a temporally regulated promoter or a tissue-preferred promoter. In another aspect, the DNA construct comprises a polynucleotide encoding an RNA transcript. In yet another aspect, the polynucleotide is positioned along the DNA construct in a sense or antisense orientation relative to the promoter. In one aspect, the RNA transcript induces RNA interference of a polynucleotide having a nucleic acid sequence of any one of SEQ ID NO: 1-197.

[023] In one embodiment, a method of making a transformed plant is provided comprising transforming a plant cell with a DNA construct and culturing the transformed plant cell under conditions that promote growth of a plant.

[024] In another embodiment, a plant cell is provided transformed with a DNA construct. In yet another aspect, a transgenic plant is provided

comprising a transformed plant cell. In one aspect, the transformed plant is a woody plant. In another aspect, the woody plant is a tree. In yet another aspect, the plant is of a species of Eucalyptus or Pinus. In one aspect, the transgenic plants have a phenotype which is different from a phenotype of a plant of the same species that has not been transformed with the DNA construct. In another aspect, the transgenic plant has a different phenotypic characteristic such as lignin quality, lignin structure, wood composition, wood appearance, wood density, wood strength, wood stiffness, cellulose polymerization, fiber dimensions, lumen size, proportion of rays, proportion of vessel elements, other plant components, plant cell division, plant cell development, number of cells per unit area, cell size, cell shape, cell wall composition, proportion of nonlignin cell wall phenolics, rate of wood formation, aesthetic appearance of wood, formation of stem defects, average microfibril angle, width of the S2 cell wall layer, rate of growth, rate of root formation, ratio of root to branch vegetative development, leaf area index, and leaf shape. In yet another aspect, the transgenic plant exhibits one or more traits, such as, increased drought tolerance, herbicide resistance, reduced or increased height, reduced or increased branching, enhanced cold and frost tolerance, improved vigor, enhanced color, enhanced health and nutritional characteristics, improved storage, enhanced yield, enhanced salt tolerance, enhanced resistance of the wood to decay, enhanced resistance to fungal diseases, altered attractiveness to insect pests enhanced heavy metal tolerance, increased disease tolerance, increased insect tolerance, increased water-stress tolerance, enhanced sweetness, improved texture, decreased phosphate content, increased germination, increased micronutrient uptake, improved starch composition, improved flower longevity, production of novel resins, increased or decreased cellulose content, increased or decreased lignin content, increased or decreased nonlignin cell wall phenolics and production of novel proteins or peptides, as compared to a plant of the same species that has not been transformed with the DNA construct. In another aspect, the transgenic plant exhibits one or more traits such as reduced

period of juvenility, an increased period of juvenility, propensity to form reaction wood, self-abscising branches, accelerated reproductive development or delayed reproductive development, and accelerated regeneration, as compared to a plant of the same species that has not been transformed with the DNA construct.

[025] In one embodiment, an isolated polynucleotide is provided comprising a nucleic acid sequence encoding the catalytic or substrate-binding domain of a polypeptide selected from of any one of SEQ ID NOs: 198 - 394 and in which the polynucleotide encodes a polypeptide having the activity of the polypeptide of SEQ ID NOs: 198 - 394.

[026] In one embodiment, a method of making a transformed plant is provided comprising transforming a plant cell with a DNA construct comprising at least one polynucleotide encoding the catalytic or substrate-binding domain of a polypeptide selected from of any one of SEQ ID NOs: 198 - 394 and culturing the transformed plant cell under conditions that promote growth of a plant. In one aspect, the method used a DNA construct comprises a promoter operably linked to the polynucleotide. In another aspect, the polypeptide is selected from 14-3-3 protein, 1-aminocyclopropane-i-carboxylate synthase, 1-aminocyclopropane-i-carboxylate oxidase, cyclin-dependant kinase inhibitor, cytokinin oxidase, ethylene receptor, ethylene-responsive elongation factor (EF-TS), F-box family protein, G protein-coupled receptor, GA20- oxidase, giberellic acid insensitive (GAI), gibberellin 2-oxidase, indole-3- acetaldehyde reductase, indole-3-acetonitrilase, Mago Nashi protein, MAP kinase, MAP kinase kinase, MAP kinase kinase kinase, polyphosphoinositide binding protein SSH2P, RAB11G, RAB11J, RAB5B, RAB7, RAN (GTPase activating protein), RAS-like GTP-binding protein, SNF1 -related protein kinase, steroid reductase, steroid sulfotransferase, or synaptobrevin-like protein. In one aspect, the method uses a plant cell located within plant explant tissue. In another aspect, the method produces a transgenic plant which exhibits a phenotype different from a plant of the same species that has not been transformed with the DNA construct. In another aspect, the

transgenic plant has a different phenotypic characteristic such as lignin quality, lignin structure, wood composition, wood appearance, wood density, wood strength, wood stiffness, cellulose polymerization, fiber dimensions, lumen size, proportion of rays, proportion of vessel elements, other plant components, plant cell division, plant cell development, number of cells per unit area, cell size, cell shape, cell wall composition, proportion of nonlignin cell wall phenolics, rate of wood formation, aesthetic appearance of wood, formation of stem defects, average microfibril angle, width of the S2 cell wall layer, rate of growth, rate of root formation ratio of root to branch vegetative development, leaf area index, and leaf shape. In yet another aspect, the transgenic plant exhibits one or more traits, such as, increased drought tolerance, herbicide resistance, reduced or increased height, reduced or increased branching, enhanced cold and frost tolerance, improved vigor, enhanced color, enhanced health and nutritional characteristics, improved storage, enhanced yield, enhanced salt tolerance, enhanced resistance of the wood to decay, enhanced resistance to fungal diseases, altered attractiveness to insect pests enhanced heavy metal tolerance, increased disease tolerance, increased insect tolerance, increased water-stress tolerance, enhanced sweetness, improved texture, decreased phosphate content, increased germination, increased micronutrient uptake, improved starch composition, improved flower longevity, production of novel resins, increased or decreased cellulose content, increased or decreased lignin content, increased or decreased nonlignin cell wall phenolics and production of novel proteins or peptides, as compared to a plant of the same species that has not been transformed with the DNA construct. In another aspect, the transgenic plant exhibits one or more traits such as reduced period of juvenility, an increased period of juvenility, propensity to form reaction wood, self-abscising branches, accelerated reproductive development or delayed reproductive development, and accelerated regeneration, as compared to a plant of the same species that has not been transformed with the DNA construct.

[027] In one embodiment, wood obtained from a transgenic plant transformed by a DNA construct is provided. In another embodiment, wood pulp obtained from a transgenic plant transformed by a DNA construct is provided.

[028] In another embodiment, a method of making wood is provided comprising transforming a plant with a DNA construct comprising a polynucleotide having a nucleic acid sequence selected from SEQ ID NO: 1- 197 and conservative variants thereof, culturing the transformed plants under conditions that promote growth of the plant, and obtaining wood from the plant.

[029] In yet another embodiment, a method of making wood pulp is provided comprising transforming a plant with a DNA construct comprising a polynucleotide having a nucleic acid sequence selected from SEQ ID NO: 1- 197 and conservative variants thereof, culturing the transformed plants under conditions that promote growth of the plant, and obtaining wood pulp from the plant.

[030] In one embodiment, an isolated polypeptide is provided comprising an amino acid sequence encoded by a polynucleotide selected from SEQ ID NO: 1-197. In another embodiment, an isolated polynucleotide is provided comprising an amino acid selected from SEQ ID NO: 198-394. [031] In one embodiment, a method of altering a plant phenotype is provided comprising altering expression in the plant of a polypeptide encoded by any one of SEQ ID NO: 1-197. In one aspect, the expression of the polypeptide can be up-regulated, down-regulated, silenced, or developmentally regulated. In another aspect, the plant phenotype is selected from lignin quality, lignin structure, wood composition, wood appearance, wood density, wood strength, wood stiffness, cellulose polymerization, fiber dimensions, lumen size, proportion of rays, proportion of vessel elements, other plant components, plant cell division, plant cell development, number of cells per unit area, cell size, cell shape, cell wall composition, proportion of nonlignin cell wall phenolics, rate of wood formation, aesthetic appearance of wood, formation of

stem defects, average microfibril angle, width of the S2 cell wall layer, rate of growth, rate of root formation ratio of root to branch vegetative development, leaf area index, and leaf shape. In yet another aspect, the plant exhibits one or more traits, such as, increased drought tolerance, herbicide resistance, reduced or increased height, reduced or increased branching, enhanced cold and frost tolerance, improved vigor, enhanced color, enhanced health and nutritional characteristics, improved storage, enhanced yield, enhanced salt tolerance, enhanced resistance of the wood to decay, enhanced resistance to fungal diseases, altered attractiveness to insect pests enhanced heavy metal tolerance, increased disease tolerance, increased insect tolerance, increased water-stress tolerance, enhanced sweetness, improved texture, decreased phosphate content, increased germination, increased micronutrient uptake, improved starch composition, improved flower longevity, production of novel resins, increased or decreased cellulose content, increased or decreased lignin content, increased or decreased nonlignin cell wall phenolics and production of novel proteins or peptides, as compared to a plant of the same species that has not been transformed with the DNA construct. In another aspect, the transgenic plant exhibits one or more traits suach as reduced period of juvenility, an increased period of juvenility, propensity to form reaction wood, self-abscising branches, accelerated reproductive development or delayed reproductive development, and accelerated regeneration, as compared to a plant of the same species that has not been transformed with the DNA construct.

[032] In one embodiment, a polynucleotide is provided comprising a nucleic acid selected from SEQ ID NO: 395-583. In one aspect, the polynucleotide comprises less than about 100 nucleotide bases.

[033] In another embodiment, a method of correlating gene expression in two different samples is provided comprising detecting a level of expression of one or more genes encoding a product encoded by a nucleic acid sequence selected from SEQ ID NOs: 1-197 and conservative variants thereof in a first sample, detecting a level of expression of the one or more genes in a second

sample, comparing the level of expression of the one or more genes in the first sample to the level of expression of the one or more genes in the second sample, and correlating a difference in expression level of the one or more genes between the first and second samples. In one aspect, the first sample and the second sample are each from a different type of plant tissue. In another aspect, the first sample and the second sample are from the same tissue, and each sample is harvested during a different season of the year. In yet another aspect, the first sample and the second sample are obtained from plants in different stages of development. In one aspect, the first sample is obtained from a plant not exposed to 'an environmental stimulus, and the second sample is obtained from a plant exposed to an environmental stimulus. In another aspect, the environmental stimulus is selected from the group consisting of change in temperature, change in amount of light, change in availability of water, change in availability of nutrients, change in availability of atmospheric gases, frost, wounding from mechanical injury, and wounding from attack by an insect, fungus, bacteria or virus.

[034] In one embodiment, a method of correlating the possession of a plant phenotype to the level of gene expression in the plant of one or more genes is provided comprising detecting a level of expression of one or more genes encoding a product encoded by a nucleic acid sequence selected from SEQ ID NOs: 1-197 and conservative variants thereof in a first plant possessing a phenotype, detecting a level of expression of the one or more genes in a second plant lacking the phenotype, comparing the level of expression of the one or more genes in the first plant to the level of expression of the one or more genes in the second plant, and correlating a difference in expression level of the one or more genes between the first and second plants to possession of the phenotype.

[035] In another embodiment, a method of correlating gene expression to a response to an external stimulus or environmental condition is provided comprising detecting a level of expression of one or more genes encoding a product encoded by a nucleic acid sequence selected from the group

consisting of SEQ ID NOs: 1-197 and conservative variants thereof in a first plant cell in the absence of the external stimulus or environmental condition, detecting a level of expression of the one or more genes in a second plant cell in the presence of the external stimulus or environmental condition, comparing the level of the expression of the one or more genes in the first plant cells to the level of expression of the one or more genes in the second plants cells; and correlating a difference in expression level of the one or more genes between the first and second samples to presence of the external stimulus or environmental condition. In one aspect, the first and second samples are both obtained from a plant tissue such as vascular tissue, apical meristem, vascular cambium, xylem, phloem, root, flower, cone, fruit, or seed. In another aspect, the plant tissue of the first sample and second samples are each obtained from a different type of tissues. In yet another aspect, the first and second samples are each obtained from a plant tissue in a different stage of development. In one aspect, the external stimulus is selected from the group consisting of change in temperature, change in amount of light, change in availability of water, change in availability of nutrients, wounding from mechanical injury, and wounding from attack by pathogens. [036] In one embodiment, there are methods provided in which the first and second plants or plant cells are of a species selected from Eucalyptus and Pinus species. In one aspect, the first and second plants or plant cells are of a species selected from Eucalyptus grandis or Pinus radiata. [037] In one embodiment, there are methods provided in which the step of detecting is effected using one or more polynucleotides capable of hybridizing to a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-197 under standard hybridization conditions. In one aspect, the step of detecting is effected using one or more polynucleotides capable of hybridizing to a nucleic acid sequence encoded by a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-197 under standard hybridization conditions. In another aspect, the step of detecting is effected by hybridization to a labeled nucleic acid. In yet another aspect, the one or

more polynucleotides are labeled with a detectable label. In one aspect, at least one of the one or more polynucleotides hybridizes to a 3' untranslated region of one of the one or more genes. In another aspect, at least one of the one or more polynucleotides hybridizes to the 3' untranslated region of one of the one or more genes. In one aspect, the one or more polynucleotides comprise a nucleic acid sequence selected from SEQ ID NOs: 395-583. In another aspect, the one or more polynucleotides comprise a nucleic acid sequence selected from SEQ ID NOs: 395-583. In yet another aspect, the one or more polynucleotides is selected from DNA or RNA. In one aspect, the methods further comprise, prior to the detecting steps, the step of amplifying the one or more genes in the first and second plant or plant cells. In another aspect, the methods further comprise, prior to the detecting steps, the step of labeling the one or more genes in the first and second plant or plant cells with a detectable label.

[038] In one embodiment, a combination for detecting expression of one or more genes is provided comprising two or more oligonucleotides. In one aspect, each oligonucleotide is capable of hybridizing to a nucleic acid sequence selected from SEQ ID NOs: 1-197. In one aspect, each of the two or more oligonucleotides hybridizes to a nucleotide sequence encoded by a different one of the nucleic acid sequences selected from SEQ ID NOs: 1-197. In another aspect, at least one of the two or more oligonucleotides hybridizes to a 3' untranslated region of a nucleic acid sequence selected from SEQ ID NOs: 1-197. In one aspect, each of the two or more oligonucleotides are comprised of fewer than about 100 nucleotide bases. In another aspect, at least one of the two or more oligonucleotides comprises a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 395-583. In one aspect, each of the two or more oligonucleotides hybridizes to a gene encoding a protein selected from a 14-3-3 protein, 1-aminocyclopropane-1- carboxylate synthase, 1-aminocyclopropane-i-carboxylate oxidase, cyclin- dependant kinase inhibitor, cytokinin oxidase, ethylene receptor, ethylene- responsive elongation factor (EF-TS), F-box family protein, G protein-coupled

receptor, GA20-oxidase, giberellic acid insensitive (GAI), gibberellin 2- oxidase, indole-3-acetaldehyde reductase, indole-3-acetonitrilase, Mago Nashi protein, MAP kinase, MAP kinase kinase, MAP kinase kinase kinase, polyphosphoinositide binding protein SSH2P, RAB11G, RAB11J, RAB5B, RAB7, RAN (GTPase activating protein), RAS-like GTP-binding protein, SNF1 -related protein kinase, steroid reductase, steroid sulfotransferase, and synaptobrevin-like protein. In another aspect, each of the two or more oligonucleotides hybridizes to a gene encoding a different one of the proteins. In one aspect, each of the two or more oligonucleotides hybridizes to a different gene. In yet another aspect, the combination comprises from about 2 to about 5000 of the two or more oligonucleotides. In one embodiment, each of the two or more oligonucleotides is labeled with a detectable label. [039] In another embodiment, a combination for detecting expression of one or more genes is provided comprising two or more oligonucleotides. In one aspect, each oligonucleotide is capable of hybridizing to a nucleic acid sequence encoded by a nucleic acid sequence selected from SEQ ID NOs: 1- 197. In another aspect, each of the two or more oligonucleotides hybridizes to a different one of the nucleic acid sequences selected from SEQ ID NOs: 1- 197. In yet another aspect, at least one of the two or more oligonucleotides hybridizes to a 3' untranslated region of a nucleic acid sequence selected from SEQ ID NOs: 1-197. In one aspect, each of the two or more oligonucleotides are comprised of fewer than about 100 nucleotide bases. In another aspect, at least one of the two or more oligonucleotides comprises a nucleic acid sequence selected from the group consisting of SEQ ID NOs 395-583. In another aspect, each of the two or more oligonucleotides hybridizes to a nucleic acid sequence encoded by a gene encoding a protein selected from a 14-3-3 protein, 1-aminocyclopropane-i-carboxylate synthase, 1-aminocyclopropane-i-carboxylate oxidase, cyclin-dependant kinase inhibitor, cytokinin oxidase, ethylene receptor, ethylene-responsive elongation factor (EF-TS), F-box family protein, G protein-coupled receptor, GA20- oxidase, giberellic acid insensitive (GAI), gibberellin 2-oxidase, indole-3-

acetaldehyde reductase, indole-3-acetonitrilase, Mago Nashi protein, MAP kinase, MAP kinase kinase, MAP kinase kinase kinase, polyphosphoinositide binding protein SSH2P, RAB11G, RAB11J, RAB5B, RAB7, RAN (GTPase activating protein), RAS-like GTP-binding protein, SNF1 -related protein kinase, steroid reductase, steroid sulfotransferase, and synaptobrevin-like protein. In one aspect, each of the two or more oligonucleotides hybridizes to a nucleic acid sequence encoded by a gene encoding a different one of the proteins. In another aspect, each of the two or more oligonucleotides hybridizes to a nucleic acid sequence encoded by a different gene. In yet another aspect, the combination comprises from about 2 to about 5000 of the two or more oligonucleotides. In one embodiment, each of the two or more oligonucleotides is labeled with a detectable label.

[040] In one embodiment, a microarray is provided comprising a combination described above provided on a solid support, wherein each of said two or more oligonucleotides occupies a unique location on said solid support. [041] In another embodiment, a method for detecting one or more genes in a sample is provided comprising contacting the sample with two or more oligonucleotides, and detecting the one or more genes of interest which are hybridized to the one or more oligonucleotides. In one aspect, each oligonucleotide is capable of hybridizing to a gene comprising a nucleic acid sequence selected from SEQ ID NOs: 1-197 under standard hybridization conditions. In another aspect, each of the two or more oligonucleotides hybridizes to a gene comprising a different one of the nucleic acid sequences selected from SEQ ID NOs: 1-197. In one aspect, at least one of the two or more oligonucleotides hybridizes to a 3' untranslated region of a gene comprising a nucleic acid sequence selected from SEQ ID NOs: 1-197. In another aspect, each of the two or more oligonucleotides are comprised of fewer than about 100 nucleotide bases. In one aspect, at least one of the two or more oligonucleotides comprises a nucleic acid sequence selected from the group consisting of SEQ ID NOs 395-583. In another aspect, each of the two or more oligonucleotides hybridizes to a gene encoding a protein selected

from the group consisting of a 14-3-3 protein, 1-aminocyclopropane-1- carboxylate synthase, i-aminocyclopropane-i-carboxylate oxidase, cyclin- dependant kinase inhibitor, cytokinin oxidase, ethylene receptor, ethylene- responsive elongation factor (EF-TS), F-box family protein, G protein-coupled receptor, GA20-oxidase, giberellic acid insensitive (GAI), gibberellin 2- oxidase, indole-3-acetaldehyde reductase, indole-3-acetonitrilase, Mago Nashi protein, MAP kinase, MAP kinase kinase, MAP kinase kinase kinase, polyphosphoinositide binding protein SSH2P, RAB11G, RAB11J, RAB5B, RAB7, RAN (GTPase activating protein), RAS-like GTP-binding protein, SNF1 -related protein kinase, steroid reductase, steroid sulfotransferase, and synaptobrevin-like protein. In a further aspect, each of the two or more oligonucleotides hybridizes to a gene encoding a different one of the proteins. In another aspect, the two or more oligonucleotides are provided on a solid support, wherein each of the two of more oligonucleotides occupy a unique location on the solid support. In yet another aspect, the solid support comprises from about 2 to about 5000 of the two or more oligonucleotides. In one aspect, the method further comprises prior to the contacting step, the step of amplifying the one or more genes or nucleic acid sequences in the sample. In another aspect, the methods further comprises , prior to the contacting step, the step of labeling the one or more genes or nucleic acid sequences in the sample with a detectable label.

[042] In yet another embodiment, a method for detecting one or more nucleic acid sequences encoded by one or more genes in a sample is provided comprising contacting the sample with two or more oligonucleotides and detecting the one or more nucleic acid sequences which are hybridized to the one or more oligonucleotides. In one aspect, each oligonucleotide is capable of hybridizing to a nucleic acid sequence encoded by a gene comprising a nucleic acid sequence selected from SEQ ID NOs: 1-197 under standard hybridization conditions. In another aspect, each of the two or more oligonucleotides hybridizes to a gene comprising a different one of the nucleic acid sequences selected from SEQ ID NOs: 1-197. In yet another aspect,

each of the two or more oligonucleotides hybridizes to a nucleic acid sequence encoded by a gene comprising a different one of the nucleic acid sequences selected from SEQ ID NOs: 1-197. In one aspect, at least one of the two or more oligonucleotides hybridizes to a nucleic acid sequence that is complementary to a 3' untranslated region of a gene comprising a nucleic acid sequence selected from SEQ ID NOs: 1-197. In another aspect, each of the two or more oligonucleotides are comprised of fewer than about 100 nucleotide bases. In one aspect, at least one of the two or more oligonucleotides comprises a nucleic acid sequence selected from the group consisting of SEQ ID NOs 395-583. In another aspect, each of the two or more oligonucleotides hybridizes to a gene encoding a protein selected from the group consisting of a 14-3-3 protein, 1-aminocyclopropane-i-carboxylate synthase, 1-aminocyclopropane-1-carboxylate oxidase, cyclin-dependant kinase inhibitor, cytokinin oxidase, ethylene receptor, ethylene-responsive elongation factor (EF-TS), F-box family protein, G protein-coupled receptor, GA20-oxidase, giberellic acid insensitive (GAI), gibberellin 2-oxidase, indole- 3-acetaldehyde reductase, indole-3-acetonitrilase, Mago Nashi protein, MAP kinase, MAP kinase kinase, MAP kinase kinase kinase, polyphosphoinositide binding protein SSH2P, RAB11G, RAB11J, RAB5B, RAB7, RAN (GTPase activating protein), RAS-like GTP-binding protein, SNF1 -related protein kinase, steroid reductase, steroid sulfotransferase, and synaptobrevin-like protein. In a further aspect, each of the two or more oligonucleotides hybridizes to a nucleic acid sequence encoded by a gene encoding a different one of the proteins. In another aspect, the two or more oligonucleotides are provided on a solid support, wherein each of the two of more oligonucleotides occupy a unique location on the solid support. In yet another aspect, the solid support comprises from about 2 to about 5000 of the two or more oligonucleotides. In one aspect, the method further comprises prior to the contacting step, the step of amplifying the one or more genes or nucleic acid sequences in the sample. In another aspect, the methods further comprises,

prior to the contacting step, the step of labeling the one or more genes or nucleic acid sequences in the sample with a detectable label.

[043] In one embodiment, a kit for detecting gene expression is provided comprising the microarray described above together with one or more buffers or reagents for a nucleotide hybridization reaction.

[044] Other features, objects, and advantages of the present invention are apparent from the detailed description that follows. It should be understood, however, that the detailed description, while indicating preferred embodiments of the invention, are given by way of illustration only, not limitation. Various changes and modifications within the spirit and scope of the invention will be apparent to those skilled in the art from the detailed description.

BRIEF DESCRIPTION OF THE DRAWINGS

[045] Figure 1 shows the annotated amino acid sequence of SEQ ID NO:

198.

[046] Figure 2 shows the annotated amino acid sequence of SEQ ID NO:

199.

[047] Figure 3 shows the annotated amino acid sequence of SEQ ID NO:

200.

[048] Figure 4 shows the annotated amino acid sequence of SEQ ID NO:

201.

[049] Figure 5 shows the annotated amino acid sequence of SEQ ID NO:

206.

[050] Figure 6 shows the annotated amino acid sequence of SEQ ID NO:

207.

[051] Figure 7 shows the annotated amino acid sequence of SEQ ID NO:

208.

[052] Figure 8 shows the annotated amino acid sequence of SEQ ID NO:

227.

[053] Figure 9 shows the annotated amino acid sequence of SEQ ID NO:

283.

[054] Figure 10 shows the annotated amino acid sequence of SEQ ID NO:

290.

[055] Figure 11 shows the annotated amino acid sequence of SEQ ID NO:

296.

[056] Figure 12 shows the annotated amino acid sequence of SEQ ID NO:

307.

[057] Figure 13 shows the annotated amino acid sequence of SEQ ID NO:

308.

[058] Figure 14 shows the annotated amino acid sequence of SEQ ID NO:

309.

[059] Figure 15 shows the annotated amino acid sequence of SEQ ID NO:

320.

[060] Figure 16 shows the annotated amino acid sequence of SEQ ID NO:

377.

[061] Figure 17 shows the annotated amino acid sequence of SEQ ID NO:

382.

[062] Figure 18 shows the annotated amino acid sequence of SEQ ID NO:

388.

[063] Figure 19 shows the annotated amino acid sequence of SEQ ID NO:

389.

[064] Figure 20 shows the annotated amino acid sequence of SEQ ID NO:

392.

[065] Figure 21 shows the annotated amino acid sequence of SEQ ID NO:

230.

[066] Figure 22 shows the annotated amino acid sequence of SEQ ID NO:

231.

[067] Figure 23 shows the annotated amino acid sequence of SEQ ID NO:

265.

[068] Figure 24 shows the annotated amino acid sequence of SEQ ID NO:

269.

[069] Figure 25 shows the annotated amino acid sequence of SEQ ID NO:

273.

[070] Figure 26 shows the annotated amino acid sequence of SEQ ID NO:

278.

[071] Figure 27 shows the annotated amino acid sequence of SEQ ID NO:

316.

[072] Figure 28 shows the annotated amino acid sequence of SEQ ID NO:

317.

[073] Figure 29 shows the annotated amino acid sequence of SEQ ID NO:

355.

[074] Figure 30 shows the annotated amino acid sequence of SEQ ID NO:

372.

[075] Figure 31 shows the annotated amino acid sequence of SEQ ID NO:

390.

[076] Figure 32 shows the annotated amino acid sequence of SEQ ID NO:

247.

[077] Figure 33 shows the annotated amino acid sequence of SEQ ID NO:

346.

[078] Figure 34 shows the annotated amino acid sequence of SEQ ID NO:

368.

[079] Figure 35 shows the annotated amino acid sequence of SEQ ID NO:

214.

[080] Figure 36 shows the annotated amino acid sequence of SEQ ID NO:

274.

[081] Figure 37 shows the annotated amino acid sequence of SEQ ID NO:

349.

[082] Figure 38 shows the annotated amino acid sequence of SEQ ID NO:

314.

[083] Figure 39 shows the annotated amino acid sequence of SEQ ID NO:

213.

[084] Figure 40 shows the annotated amino acid sequence of SEQ ID NO:

222.

[085] Figure 41 shows the annotated amino acid sequence of SEQ ID NO:

224.

[086] Figure 42 shows the annotated amino acid sequence of SEQ ID NO:

228.

[087] Figure 43 shows the annotated amino acid sequence of SEQ ID NO:

232.

[088] Figure 44 shows the annotated amino acid sequence of SEQ ID NO:

236.

[089] Figure 45 shows the annotated amino acid sequence of SEQ ID NO:

237.

[090] Figure 46 shows the annotated amino acid sequence of SEQ ID NO:

252.

[091] Figure 47 shows the annotated amino acid sequence of SEQ ID NO:

253.

[092] Figure 48 shows the annotated amino acid sequence of SEQ ID NO:

256.

[093] Figure 49 shows the annotated amino acid sequence of SEQ ID NO:

259.

[094] Figure 50 shows the annotated amino acid sequence of SEQ ID NO:

263.

[095] Figure 51 shows the annotated amino acid sequence of SEQ ID NO:

268.

[096] Figure 52 shows the annotated amino acid sequence of SEQ ID NO:

271.

[097] Figure 53 shows the annotated amino acid sequence of SEQ ID NO:

284.

[098] Figure 54 shows the annotated amino acid sequence of SEQ ID NO:

286.

[099] Figure 55 shows the annotated amino acid sequence of SEQ ID NO:

293.

[100] Figure 56 shows the annotated amino acid sequence of SEQ ID NO:

294.

[101] Figure 57 shows the annotated amino acid sequence of SEQ ID NO:

305.

[102] Figure 58 shows the annotated amino acid sequence of SEQ ID NO:

323.

[103] Figure 59 shows the annotated amino acid sequence of SEQ ID NO:

336.

[104] Figure 60 shows the annotated amino acid sequence of SEQ ID NO:

343.

[105] Figure 61 shows the annotated amino acid sequence of SEQ ID NO:

351.

[106] Figure 62 shows the annotated amino acid sequence of SEQ ID NO:

360.

[107] Figure 63 shows the annotated amino acid sequence of SEQ ID NO:

363.

[108] Figure 64 shows the annotated amino acid sequence of SEQ ID NO:

366.

[109] Figure 65 shows the annotated amino acid sequence of SEQ ID NO:

369.

[110] Figure 66 shows the annotated amino acid sequence of SEQ ID NO:

373.

[111] Figure 67 shows the annotated amino acid sequence of SEQ ID NO:

380.

[112] Figure 68 shows the annotated amino acid sequence of SEQ ID NO:

385.

[113] Figure 69 shows the annotated amino acid sequence of SEQ ID NO:

394.

[114] Figure 70 shows the annotated amino acid sequence of SEQ ID NO:

262.

[115] Figure 71 shows the annotated amino acid sequence of SEQ ID NO:

272.

[116] Figure 72 shows the annotated amino acid sequence of SEQ ID NO:

347.

[117] Figure 73 shows the annotated amino acid sequence of SEQ ID NO:

240.

[118] Figure 74 shows the annotated amino acid sequence of SEQ ID NO:

223.

[119] Figure 75 shows the annotated amino acid sequence of SEQ ID NO:

313.

[120] Figure 76 shows the annotated amino acid sequence of SEQ ID NO:

374.

[121] Figure 77 shows the annotated amino acid sequence of SEQ ID NO:

279.

[122] Figure 78 shows the annotated amino acid sequence of SEQ ID NO:

288.

[123] Figure 79 shows the annotated amino acid sequence of SEQ ID NO:

370.

[124] Figure 80 shows the annotated amino acid sequence of SEQ ID NO:

202.

[125] Figure 81 shows the annotated amino acid sequence of SEQ ID NO:

203.

[126] Figure 82 shows the annotated amino acid sequence of SEQ ID NO:

204.

[127] Figure 83 shows the annotated amino acid sequence of SEQ ID NO:

258.

[128] Figure 84 shows the annotated amino acid sequence of SEQ ID NO:

311.

[129] Figure 85 shows the annotated amino acid sequence of SEQ ID NO:

312.

[130] Figure 86 shows the annotated amino acid sequence of SEQ ID NO:

364.

[131] Figure 87 shows the annotated amino acid sequence of SEQ ID NO:

212.

[132] Figure 88 shows the annotated amino acid sequence of SEQ ID NO:

353.

[133] Figure 89 shows the annotated amino acid sequence of SEQ ID NO:

238.

[134] Figure 90 shows the annotated amino acid sequence of SEQ ID NO:

325.

[135] Figure 91 shows the annotated amino acid sequence of SEQ ID NO:

326.

[136] Figure 92 shows the annotated amino acid sequence of SEQ ID NO:

220.

[137] Figure 93 shows the annotated amino acid sequence of SEQ ID NO:

221.

[138] Figure 94 shows the annotated amino acid sequence of SEQ ID NO:

234.

[139] Figure 95 shows the annotated amino acid sequence of SEQ ID NO:

235.

[140] Figure 96 shows the annotated amino acid sequence of SEQ ID NO:

248.

[141] Figure 97 shows the annotated amino acid sequence of SEQ ID NO:

299.

[142] Figure 98 shows the annotated amino acid sequence of SEQ ID NO:

315.

[143] Figure 99 shows the annotated amino acid sequence of SEQ ID NO:

324.

[144] Figure 100 shows the annotated amino acid sequence of SEQ ID NO:

334.

[145] Figure 101 shows the annotated amino acid sequence of SEQ ID NO:

342.

[146] Figure 102 shows the annotated amino acid sequence of SEQ ID NO:

344.

[147] Figure 103 shows the annotated amino acid sequence of SEQ ID NO:

356.

[148] Figure 104 shows the annotated amino acid sequence of SEQ ID NO:

359.

[149] Figure 105 shows the annotated amino acid sequence of SEQ ID NO:

367.

[150] Figure 106 shows the annotated amino acid sequence of SEQ ID NO:

209.

[151] Figure 107 shows the annotated amino acid sequence of SEQ ID NO:

244.

[152] Figure 108 shows the annotated amino acid sequence of SEQ ID NO:

261.

[153] Figure 109 shows the annotated amino acid sequence of SEQ ID NO:

297.

[154] Figure 110 shows the annotated amino acid sequence of SEQ ID NO:

341.

[155] Figure 111 shows the annotated amino acid sequence of SEQ ID NO:

358.

[156] Figure 112 shows the annotated amino acid sequence of SEQ ID NO:

365.

[157] Figure 113 shows the annotated amino acid sequence of SEQ ID NO:

250.

[158] Figure 114 shows the annotated amino acid sequence of SEQ ID NO:

280.

[159] Figure 115 shows the annotated amino acid sequence of SEQ ID NO:

330.

[160] Figure 116 shows the annotated amino acid sequence of SEQ ID NO:

331.

[161] Figure 117 shows the annotated amino acid sequence of SEQ ID NO:

357.

[162] Figure 118 shows the annotated amino acid sequence of SEQ ID NO:

375.

[163] Figure 119 shows the annotated amino acid sequence of SEQ ID NO:

266.

[164] Figure 120 shows the annotated amino acid sequence of SEQ ID NO:

327.

[165] Figure 121 shows the annotated amino acid sequence of SEQ ID NO:

257.

[166] Figure 122 shows the annotated amino acid sequence of SEQ ID NO:

319.

[167] Figure 123 shows the annotated amino acid sequence of SEQ ID NO:

329.

[168] Figure 124 shows the annotated amino acid sequence of SEQ ID NO:

361.

[169] Figure 125 shows the annotated amino acid sequence of SEQ ID NO:

210.

[170] Figure 126 shows the annotated amino acid sequence of SEQ ID NO:

211.

[171] Figure 127 shows the annotated amino acid sequence of SEQ ID NO:

354.

[172] Figure 128 shows the annotated amino acid sequence of SEQ ID NO:

362.

[173] Figure 129 shows the annotated amino acid sequence of SEQ ID NO:

300.

[174] Figure 130 shows the annotated amino acid sequence of SEQ ID NO:

301.

[175] Figure 131 shows the annotated amino acid sequence of SEQ ID NO:

233.

[176] Figure 132 shows the annotated amino acid sequence of SEQ ID NO:

264.

[177] Figure 133 shows the annotated amino acid sequence of SEQ ID NO:

267.

[178] Figure 134 shows the annotated amino acid sequence of SEQ ID NO:

298.

[179] Figure 135 shows the annotated amino acid sequence of SEQ ID NO:

376.

[180] Figure 136 shows the annotated amino acid sequence of SEQ ID NO:

205.

[181] Figure 137 shows the annotated amino acid sequence of SEQ ID NO:

215.

[182] Figure 138 shows the annotated amino acid sequence of SEQ ID NO:

241.

[183] Figure 139 shows the annotated amino acid sequence of SEQ ID NO:

285.

[184] Figure 140 shows the annotated amino acid sequence of SEQ ID NO:

291.

[185] Figure 141 shows the annotated amino acid sequence of SEQ ID NO:

292.

[186] Figure 142 shows the annotated amino acid sequence of SEQ ID NO:

302.

[187] Figure 143 shows the annotated amino acid sequence of SEQ ID NO:

303.

[188] Figure 144 shows the annotated amino acid sequence of SEQ ID NO:

304.

[189] Figure 145 shows the annotated amino acid sequence of SEQ ID NO:

350.

[190] Figure 146 shows the annotated amino acid sequence of SEQ ID NO:

245.

[191] Figure 147 shows the annotated amino acid sequence of SEQ ID NO:

260.

[192] Figure 148 shows the annotated amino acid sequence of SEQ ID NO:

381.

[193] Figure 149 shows the annotated amino acid sequence of SEQ ID NO:

216.

[194] Figure 150 shows the annotated amino acid sequence of SEQ ID NO:

217.

[195] Figure 151 shows the annotated amino acid sequence of SEQ ID NO:

218.

[196] Figure 152 shows the annotated amino acid sequence of SEQ ID NO:

219.

[197] Figure 153 shows the annotated amino acid sequence of SEQ ID NO:

226.

[198] Figure 154 shows the annotated amino acid sequence of SEQ ID NO:

229.

[199] Figure 155 shows the annotated amino acid sequence of SEQ ID NO:

239.

[200] Figure 156 shows the annotated amino acid sequence of SEQ ID NO:

255.

[201] Figure 157 shows the annotated amino acid sequence of SEQ ID NO:

275.

[202] Figure 158 shows the annotated amino acid sequence of SEQ ID NO:

306.

[203] Figure 159 shows the annotated amino acid sequence of SEQ ID NO:

318.

[204] Figure 160 shows the annotated amino acid sequence of SEQ ID NO:

322.

[205] Figure 161 shows the annotated amino acid sequence of SEQ ID NO:

335.

[206] Figure 162 shows the annotated amino acid sequence of SEQ ID NO:

348.

[207] Figure 163 shows the annotated amino acid sequence of SEQ ID NO:

383.

[208] Figure 164 shows the annotated amino acid sequence of SEQ ID NO:

387.

[209] Figure 165 shows the annotated amino acid sequence of SEQ ID NO:

393.

[210] Figure 166 shows the annotated amino acid sequence of SEQ ID NO:

225.

[211] Figure 167 shows the annotated amino acid sequence of SEQ ID NO:

310.

[212] Figure 168 shows the annotated amino acid sequence of SEQ ID NO:

242.

[213] Figure 169 shows the annotated amino acid sequence of SEQ ID NO:

243.

[214] Figure 170 shows the annotated amino acid sequence of SEQ ID NO:

281.

[215] Figure 171 shows the annotated amino acid sequence of SEQ ID NO:

287.

[216] Figure 172 shows the annotated amino acid sequence of SEQ ID NO:

289.

[217] Figure 173 shows the annotated amino acid sequence of SEQ ID NO:

328.

[218] Figure 174 shows the annotated amino acid sequence of SEQ ID NO:

332.

[219] Figure 175 shows the annotated amino acid sequence of SEQ ID NO:

333.

[220] Figure 176 shows the annotated amino acid sequence of SEQ ID NO:

345.

[221] Figure 177 shows the annotated amino acid sequence of SEQ ID NO:

378.

[222] Figure 178 shows the annotated amino acid sequence of SEQ ID NO:

384.

[223] Figure 179 shows the annotated amino acid sequence of SEQ ID NO:

386.

[224] Figure 180 shows the annotated amino acid sequence of SEQ ID NO:

270.

[225] Figure 181 shows the annotated amino acid sequence of SEQ ID NO:

276.

[226] Figure 182 shows the annotated amino acid sequence of SEQ ID NO:

282.

[227] Figure 183 shows the annotated amino acid sequence of SEQ ID NO:

339.

[228] Figure 184 shows the annotated amino acid sequence of SEQ ID NO:

246.

[229] Figure 185 shows the annotated amino acid sequence of SEQ ID NO:

249.

[230] Figure 186 shows the annotated amino acid sequence of SEQ ID NO:

251.

[231] Figure 187 shows the annotated amino acid sequence of SEQ ID NO:

254.

[232] Figure 188 shows the annotated amino acid sequence of SEQ ID NO:

277.

[233] Figure 189 shows the annotated amino acid sequence of SEQ ID NO:

295.

[234] Figure 190 shows the annotated amino acid sequence of SEQ ID NO:

321.

[235] Figure 191 shows the annotated amino acid sequence of SEQ ID NO:

337.

[236] Figure 192 shows the annotated amino acid sequence of SEQ ID NO:

338.

[237] Figure 193 shows the annotated amino acid sequence of SEQ ID NO:

340.

[238] Figure 194 shows the annotated amino acid sequence of SEQ ID NO:

352.

[239] Figure 195 shows the annotated amino acid sequence of SEQ ID NO:

379.

[240] Figure 196 shows the annotated amino acid sequence of SEQ ID NO:

391.

[241] Figure 197 shows the annotated amino acid sequence of SEQ ID NO:

371.

[242] Figure 198 shows a graphic representation of the DNA construct pWVR202.

[243] Figure 199 shows a graphic representation of the DNA construct pGrowthi .

[244] Figure 200 shows a graphic representation of the DNA construct pGrowth2.

[245] Figure 201 shows a graphic representation of the DNA construct pGrowth11.

[246] Figure 202 shows a graphic representation of the DNA construct pGrowth21.

[247] Figure 203 shows a graphic representation of the DNA construct pGrowth22.

[248] Figure 204 shows a graphic representation of the DNA construct pGrowth23.

[249] Figure 205 shows a graphic representation of the DNA construct pGrowth24.

[250] Figure 206 shows a graphic representation of the DNA construct pGrowth25.

[251] Figure 207 shows a graphic representation of the DNA construct pGrowth26.

[252] Figure 208 shows a graphic representation of the DNA construct pGrowth27.

[253] Figure 209 shows a graphic representation of the DNA construct pGrowth28.

[254] Figure 210 shows a graphic representation of the DNA construct pGrowth30.

[255] Figure 211 shows a graph of the percentage of shoot lines from each line of plants transformed in Example 16.

[0256] Figure 212 shows a graphic representation of the DNA construct pGrowth3.

[0257] Figure 213 shows a graphic representation of the DNA construct pGrowth29.

[0258] Figure 214 shows a graphic representation of the DNA construct pGrowth49.

[0259] Figure 215 shows a graphic representation of the DNA construct pGrowth51.

DETAILED DESCRIPTION

[260] Novel isolated cell signaling genes and polynucleotides useful for identifying the multigenic factors that contribute to a phenotype and for manipulating gene expression to effect a plant phenotype are provided. These genes, which are derived from plants of commercially important forestry genera, pine and eucalyptus, are involved in the plant signal transduction and are, at least in part, responsible for expression of phenotypic characteristics important in commercial wood, such as stiffness, strength,

density, fiber dimensions, coarseness, cellulose and lignin content, and extractives content. Generally, the genes and polynucleotides encode a protein which can be a 14-3-3 protein, i-aminocyclopropane-i-carboxylate synthase, 1-aminocyclopropane-i-carboxylate oxidase, cyclin-dependant kinase inhibitor, cytokinin oxidase, ethylene receptor, ethylene-responsive elongation factor (EF-TS), F-box family protein, G protein-coupled receptor, GA20-oxidase, giberellic acid insensitive (GAI), gibberellin 2-oxidase, indole- 3-acetaldehyde reductase, indole-3-acetonitrilase, Mago Nashi protein, MAP kinase, MAP kinase kinase, MAP kinase kinase kinase, polyphosphoinositide binding protein SSH2P, RAB11G, RAB11J, RAB5B, RAB7, RAN (GTPase activating protein), RAS-like GTP-binding protein, SNF1 -related protein kinase, steroid reductase, steroid sulfotransferase, synaptobrevin-like protein or a catalytic domain thereof, or a polypeptide having the same function, the invention further includes such proteins and polypeptides. [261] The methods of the present invention for selecting cell signaling gene sequences to target for manipulation permit better design and control of transgenic plants with more highly engineered phenotypes. The ability to control plant architecture and agronomically important traits in commercially important forestry species is improved by the information obtained from the methods, such as which genes affect which phenotypes, which genes affect signal transduction, which genes are active in which stage of plant development, and which genes are expressed in which tissue at a given point in the cell cycle or plant development.

[262] Unless indicated otherwise, all technical and scientific terms are used herein in a manner that conforms to common technical usage. Generally, the nomenclature of this description and the described laboratory procedures, including cell culture, molecular genetics, and nucleic acid chemistry and hybridization, respectively, are well known and commonly employed in the art. Standard techniques are used for recombinant nucleic acid methods, oligonucleotide synthesis, cell culture, tissue culture, transformation, transfection, transduction, analytical chemistry, organic synthetic chemistry,

chemical syntheses, chemical analysis, and pharmaceutical formulation and delivery. Generally, enzymatic reactions and purification and/or isolation steps are performed according to the manufacturers' specifications. Absent an indication to the contrary, the techniques and procedures in question are performed according to conventional methodology disclosed, for example, in Sambrook et al., Molecular Cloning A Laboratory Manual. 2d ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY (1989), and F. M. Ausubel et al. (Ed.), Current Protocols in Molecular Biology. John Wiley & Sons, New York, NY (2002). Specific scientific methods relevant to the present invention are discussed in more detail below. However, this discussion is provided as an example only, and does not limit the manner in which the methods of the invention can be carried out.

I. Plant Cell Signaling Genes and Gene Products

A. Cell Signaling Genes, Polynucleotide and Polypeptide Sequences

[263] One aspect of the present invention relates to novel cell signaling genes and polypeptides encoded by such genes.

[264] The present invention provides novel plant cell signaling genes and polynucleotides and novel cell signaling proteins and polypeptides. The SEQ ID NOs of exemplary cell signaling genes and their corresponding gene products, i.e. oligonucleotides and proteins, are set forth in TABLE 1. In accordance with one embodiment of the invention, the cell signaling genes are the same as those expressed in a wild-type plant of a species of Pinus or Eucalyptus. Specific exemplary novel plant cell signaling gene sequences of the invention are set forth in TABLE 2, which comprises Eucalyptus grandis and Pinus radiata sequences. Corresponding gene products, i.e., proteins and oligonucleotides, are listed in TABLE 3 and TABLE 4. [265] Cell Signaling genes and gene products affect plant growth and development by a number of disparate mechanisms and biological pathways. Exemplary categories for some of these mechanisms and biological pathways include growth, development and phytohormone response genes, cellular

receptor and related genes and intracellular transduction genes are provided. Exemplary genes and gene products for members of these categories are also provided.

1. Growth, Development and Phytohormone Response Genes and Gene Products

[266] Ethylene Response Genes and Gene Products. Ethylene is an important phyotohormone, or plant hormone, because it is involved in virtually all stages of plant growth and development, effecting environmental and developmental responses. Ethylene participates in the regulation of processes such as germination of seeds, senescence, abscission, fruit ripening, responses to environmental stresses such as wounding, flooding, and changes in temperatures or light.

[267] Ethylene is produced from methionine via the formation of S- adenosylmethionine (SAM), which in turn forms the non-protein amino acid, 1- aminocyclopropane-1-carboxylic acid (ACC). ACC is subsequently oxidized to the 2-carbon olefin, ethylene. Two enzymes are unique to the plant ethylene biosynthetic pathway.

[268] One phytormone synthesis gene is 1-aminocyclopropane-i-carboxylate synthase. It is a pyridoxal phosphate dependent enzyme that converts SAM to ACC. Another phytormone synthesis gene is 1-aminocyclopropane-1- carboxylate oxidase. It catalyzes the oxidation of ACC to the 2-carbon olefin, ethylene. Adams and Yang, Proc. Natl. Acad. Sci. USA 76:170-174 (1979). [269] Ethylene production is tightly controlled by regulation of enzyme expression and modulation of enzyme activity dependent upon the availability of cofactors required for catalysis. ACC synthase and ACC oxidase are constituatively present in most plant tissues because small amounts of ethylene are necessary for virtually all stages of development. However, ethylene biosynthesis is increased significantly during fruit ripening. ACC synthase is considered to be the primary, though not exclusive, rate-limiting enzyme in the ethylene biosynthetic pathway, while the regulation of ethylene

production via control of ACCO expression and ACCO activity are through to fine-tune the system.

[270] Ethylene signal transduction initiates with ethylene binding at a family of ethylene receptors and terminates in a transcription cascade involving the EIN3/EIL and ERF families of plant-specific transcription factors. Two Arabidopsis F box proteins, called EBF1 and EBF2, have been identified that interact physically with EIN3/EIL transcription factors. See Potuschak et al., Ce//. 775(6) :679-89 (2003). EBF1 overexpression results in plants insensitive to ethylene.

[271] During fruit ripening, and through this mechanism, ethylene induces the expression of a number of genes and gene products. Yang & Hoffman, Annu. Rev. Plant Physiol. 35:155-189 (1984); Abeles et al., Ethylene In Plant Biology, Academic Press, San Diego (1992). For example, the ethylene- responsive elongation factor (EF-TS) is a mitochondrial elongation factor which promotes guanine nucleotide exchange during polypeptide synthesis. See Benichou et al., Plant MoI. Biol. 53^:411-22 (2003). [272] Gibberellin Response Genes and Gene Products. Another major class of phytohormone is tetracyclic diterpenoids, called Gibberellins (GA). GAs are involved in many processes during plant growth and development, including seed germination, stem elongation, flowering, and fruit development. See Hedden and Kamiya, Annu. Rev. Plant Physiol. Plant MoI. Biol. 48:431-60 (1997). Bioactive GAs are perceived at the plasma membrane of the plant cell. See Lovegrove et al., Plant J. 75:311-320 (1998). A number of potential components of the GA signaling pathway have been identified using cell biological, pharmacological, and genetic approaches. See Thornton et al., Trends Plant Sci. 4:424-428 (1999); Lovegrove and Hooley, Trends Plant Sci. 5:102-110 (2000).

[273] It is thought that de novo biosynthesis is the main source of bioactive GA in growing tissues and, as such, the enzymes are likely to be the regulators of GA-related growth. See Huang et al., Plant Physiol. 118(3):773~ 81 (1998). In Arabidopsis, there are at least five loci involved in GA

biosynthesis: GA1, GA2, GA3, GA4, and GA5. See Koornneef and van der Veen, Theor. Appl. Genet 58:257-263 (1980). For a complete review of the proposed biosynthetic pathway see Finkelstein and Zeevaart, Gibberellins and abscisic acid jn Arabidopsis (CR Somerville, EM Meyerowitz, eds.), Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, pp 523-553 (1984). Briefly, the first reaction of the GA biosynthesis pathway is the cyclization of geranylgeranyl pyrophosphate to ent-kaurene, a two-step conversion. Copalyl diphosphate synthase, formerly ent-kaurene synthetase A, the enzyme responsible for the first part of the reaction, is encoded by the GA1 locus and has been cloned. See Sun et al., Plant Cell 4:119-128 (1992). The GA2 locus encodes ent-kaurene synthase, which completes the conversion of geranylgeranyl pyrophosphate to ent-kaurene. It is thought that the GA3 locus encodes a Cyt P450 monooxygenase which catalyzes the oxidation of ent-kaurene to ent-kaurenoic acid. It is also thought that GA5 and GA4 encode GA20-oxidase and GA3-hydroxylase, respectively. Both genes have been cloned, and GA5 protein produced in vitro exhibits GA20-oxidase activity. See Chiang et al., Plant Cell 7:195-201 (1995); Xu et al., Proc. Natl. Acad. ScL U.S.A. 92:6640-6644 (1995).

[274] GA20-oxidase catalyzes what is thought to be an important aspect of the regulation of the GA biosynthetic pathway - the oxidation of GA at carbon-20. In spinach, enhanced oxidation activity is associated with the bolting response. See Gilmour et al., Plant Physiol. 82:190-195 (1986). In maize seedlings, GA20-oxidase activity is down-regulated as a result of feedback control. See Karssen et al. (eds), Progress in Plant Growth Regulation, pp 534-544, Kluwer Academic Publishers, Dordrecht, The Netherlands (1992). In Arabidopsis, GA20-oxidase is up-regulated when plants are transferred from short-day to long-day conditions. Likewise, it is down-regulated when plants are treated with bioactive GA. Accordingly, it is thought that the developmental and environmental regulation of 20-oxidase gene expression influences plant growth by affecting the level of endogenous gibberellic acid. See Huang et al., Plant Physiol. 118(3):773-8ϊ (1998).

[275] As such, catabolism of GAs is an important regulator of the endogenous levels of bioactive gibberellins. In many plant species, bioactive GA are 2-hydroxylated to produce biologically inactive proteins. This step is catalyzed by GA 2-oxidase. This enzyme also inactivates immediate precursors of bioactive GAs. See Ross et al., Plant J. 7:513-523 (1995). The expression levels of GA 2-oxidase have been correlated to the presence of bioactive GA. In total, both GA biosynthesis genes and gene products and GA catabolism genes and gene products are regulated through feedback to maintain endogenous levels of bioactive GAs. See Sakamoto et al., Plant Physiol. 125(3)λ 508-16 (2001).

[276] Arabidopsis mutants that are GA-deficient display characteristic phenotypes, including dark green leaves and a dwarf growth habit attributable to reduced stem elongation. See Peng and Harberd, Plant Physiol. 173:1051- 1058 (1997). A semidominant mutation of Arabidopsis, gibberellic acid insensitive (GAI), also confers a dark green, dwarf phenotype. It is thought that the gai mutation affects either GA perception or subsequent signal transduction. Likewise, it is thought that GAI, and its known suppressors, modulate a signal-transduction pathway that represses growth and is opposed by gibberellic acid. See Peng et al., Genes Dev. 11(23):2>λ 94-205 (1997). [277] Brassinosteroid Response Genes and Gene Products. Brassinosteroids (BRs) are widely distributed throughout the plant kingdom and elicit unique growth promoting activity when applied exogenously. Mandava, Annu. Rev. Plant Physiol. Plant MoI. Biol. 39:23-52 (1988). In many species, BR-deficient mutants show strong dwarfism with dark-green rugose leaves, reduced apical dominance and reduced male fertility. Also, Arabidopsis BR-deficient mutants have a prolonged vegetative phase and delayed leaf and chloroplast senescence. See Chory and Li, Plant Cell Environ. 20:801-806 (1997).

[278] One Arabidopsis BR-deficiency causing mutation, det2, has been cloned and shown to encode a protein analogous to mammalian steroid 5α- reductases. See Li et al., Science 272:398-401 (1996). In mammals, steroid

hormones are synthesized from cholesterol via pregnenolone through a series of reactions that modify the ring structure and the side chain of the sterol. Similarly, BRs are thought to be derived from several major phytosterols (e.g., campesterol, sitosterol, and stigmasterol) via multiple oxidation steps. In many mammalian steroid hormones, the reduction of a 4,5 double bond, as catalyzed by 5α-reductase, serves to modulate the biological activity of the steroid hormone. In contrast, known naturally occurring and biologically active BRs lack double bonds in the A and B rings and contain a 5-reduced stereochemistry. Accordingly, it is thought that a steroid 5-reductase must be required for the formation of the trans A/B ring junction that is essential for the biological activity of BRs. See Li et al., Proc. Natl. Acad. Sci. U.S.A. 94(8J:3554-59 (1997).

[279] Likewise, another Arabidopsis BR-deficiency causing mutation, cpd, has been cloned and characterized. See Szekeres et al., Cell 85:171-182 (1996). The CPD protein shares sequence homology with several mammalian cytochrome P450 proteins, including several steroid hydroxylases. Mutations in CPD cause phenotypic defects that are similar to those of det2 mutations. Moreover, brassinolide treatment restores a wild-type phenotype to cpd mutants. Accordingly, these and other studies suggest that CPD may encode a steroid 23-hydroxylase .

[280] Much like the control of mammalian steroid biological activity, it is thought that BRs are modulated through a mechanism of hormone inactivation by sulfonation. In this regard, a plant enzyme that catalyzes the O-sulfonation of brassinosteroids and of mammalian estrogenic steroids has been cloned and characterized. See Rouleau et al., J. Biol. Chem. 274(30):20925-30 (1999). This steroid sulfotransferase catalyzes a reaction which abolishes BRs biological activity in the bean second intemode bioassay. Moreover, the expression of the steroid sulfotransferase genes in some species was found to be induced by salicylic acid, a well-known signal molecule in the plant defense response. This pattern of expression suggests that, in addition to an increased synthesis of proteins having antimicrobial

properties, plants respond to pathogen infection by modulating steroid- dependent growth and developmental processes.

[281] Additionally, a large number of Arabidopsis BR-insensitive mutants have been characterized and shown to possess a mutation of the same gene. See Li and Chory, Cell 90:929-938 (1997). This gene was cloned and shown to possess homology to LRR receptor kinases. As such, it is thought that the BR steroid receptor is a LRR receptor in the plasma membrane. [282] Cvtokinin Response Genes and Gene Products. The phytohormone cytokinin plays a major role in many developmental processes and environmental responses of plants, including leaf senescence, apical dominance, chloroplast development, anthocyanin production, and the regulation of cell division and sink/source relationships. See Hutchison and Kieber, Plant Cell. 74:S47-59 (2002). Cytokinins first were identified by their ability to promote cell division in cultured cells in combination with another phytohormone, auxin. See Skoog and Miller, Symp. Soc. Exp. Biol. 77:118- 131 (1957). It is thought that the influence of cytokinins on morphogenesis is primarily achieved through cell cycle regulation. See Werner et al., Proc. Natl. Acad. Sci. USA 98(18): 10487-92 (2001). The hormone is required for S- phase entry in leaf mesophyll protoplasts and tobacco pith explants. See Cooke and Meyer, Planta 752:1-7 (1991); Mok and Mok (eds.), Cvtokinins: Chemistry, Activity and Function, CRC, Boca Raton, FL (1994). Additionally, several cell cycle genes are regulated by cytokinins, including, cdc2, CycD3, and others. See, e.g., Hemerlyet al., Plant Cell 5:1711-1723 (1993); Riou- Khamlichiet al., Science 283, 1541-1544(1999).

[283] Similar to other phytohormones, the existence of pathways for the degradation and conjugation of cytokinins suggests that the level of these compounds are tightly regulated. For example, Cytokinin oxidase catalyzes the irreversible degradation of in a single enzymatic step by oxidative side chain cleavage. See Schmulling et al., J. Plant Res. 776(3J:241-52 (2003). [284] Several of the enzymes encoding the proteins that catalyze these metabolic reactions have been cloned (see, for example, Houba-Herin et al.,

Plant J. -/7:615-626 (1999); Martin et al., Plant Physiol. 120:553-557 (1999), Martin et al., Proc. Natl. Acad. Sci. USA 96:284-289 (1999); Martin et al., Proc. Natl. Acad. Sci. USA 98:5922-5926 (2001); and Morris et al., Biochem. Biophys. Res. Commun. 255:328-333 (1999)), as have the genes encoding a key enzyme in cytokinin biosynthesis, isopentyl transferase (see Kakimoto, Science 274:982-985 (2001); Takei et al., J. Biol. Chem. 276:26405^10 (2001)). Cytokinin biosynthesis and catabolism have been reviewed in depth, for example, in Haberer and Kieber, Plant Physiol. 728:354-362 (2001) and Mok and Mok, Annu. Rev. Plant Physiol. Plant MoI. Biol. 52:89-118 (2001). [285] The cytokinin cell signal transduction pathway has also been partially elucidated. See, e.g., Hutchison and Kieber, Plant Cell 74:S47-59 (2002). Briefly, cytokinins bind to cytokinin response 1 (CRE1) histidine kinase at the cell membrane, and most likely also to the histidine kinases AHK2 and AHK3. Binding induces autophosphorylation on a Histidine residue within the receptor's transmitter domain. Subsequently, the phosphate is transferred to an Asparagine residue within the fused receiver domain. Then, this phosphate is transferred to a Histidine residue on a phosphotransfer protein (AHP). The AHP translocates to the nucleus, where it activates a response regulator (ARR). The activated ARR then binds to elements within the promoter of other ARRs to increase their rate of transcription. Some ARRs feed back to inhibit their own expression and, possibly, cytokinin signaling in general.

[286] Auxin Response Genes and Gene Products. Further, the first phytohormone discovered, Auxin, also may dramatically affect plant phenotype, growth and development. Auxin has been shown to impact a wide variety of developmental processes, such a stem elongation, apical dominance, root initiation and fruit development. Auxin was first identified as the chemical agent responsible for the phototropism of coleoptile tips. See Thiamann and Skoog, Vica faba. Proc. R. Soc. Lond. [Biol.] 774:317-339 (1934). Thiamann and Skoog, among others, discovered that auxin in higher plants is actually indole-3-acetic acid (IAA). It has been recommended that

auxins, as a class of hormones, can be defined as any compound that has a biological activity similar to, but not necessarily identical with IAA. See Salisbury (Ed.), Units, Symbols and Terminology for Plant Physiology. Oxford University Press, New York, NY (1996). These activities include, for example, the induction of cell elongation in isolated coleoptile or stem sections; the induction of cell division in callus tissues in the presence of a cytokinin; the promotion of lateral root formation at the cut surfaces of stems; the induction of parthenocarpic fruit growth; and the induction of ethylene formation. [287] Multiple IAA biosynthetic pathways exist in plants, both tryptophan- dependent and tryptophan-independent. In one pathway, called the indole-3- pyruvic acid (IPA) pathway, is thought to be the most common tryptophan- dependent biosynthetic pathway. The IPA pathway involves the deanimation of tryptophan to form IPA, followed by a decarboxylation reaction to form indole-3-acetaldehyde (lAid). IAid is then oxidized to form IAA. Alternatively, in the indole-3-acetonitrile (IAN) pathway, tryptophan is converted to indole-3- acetaldoxime and subsequently converted to IAN. A nitrilase then catalyzes the conversion of IAN to IAA.

[288] Likewise, Auxin degradation may occur through may different pathways. In one, it is thought that peroxidase enzymes catalyze the oxidation of IAA to 3-methyleneoxindole. However, the physiological significance of the peroxidase pathway is unclear. See Normanly et al., Plant Physiol. 107:323-329 (1995). Two other oxidation pathways have been proposed for the degradation of IAA. In both, the final product is oxindole-3- acetic acid. See Davies (Ed.), Plant Hormones and Their Role in Plant Growth Development (2nd ed.), Kluwer, Dordrecht, Netherlands (1995). [289] Absicisic Acid Response Genes and Gene Products. Absicisic acid (ABA) functions in initiation and maintenance of seed and bud dormancy and response to stress. ABA exerts long-term and short-term control over plant development. Long term effects are mediated by ABA induced gene expression. ABA stimulates synthesis of RAB. ABA also is involved in plant development by interacting, typically as an antagonist, with auxin, cytokinin,

and gibberellin. ABA also affects plant tolerance to water stress by preventing desiccation. Proteins which are responsive to ABA, "RAB proteins" are water soluble, rich in glycine and lysine, and low in hydrophobic residues. Rab regulates transport of proteins and RNA across nuclear envelope. Vernoud et al., supra. RAB proteins are discussed in more detail below.

2. Cellular Receptor and Related Genes and Gene Products

[290] Likewise, cell surface receptors communicate outside stimuli and serve as initiation sites for intracellular signaling cascades. For example, a family of cellular receptor genes, including ETR1 , ETR2, EIN4, ERS1 , and ERS2, has been implicated in ethylene perception in Arabidopsis thaliana. See Hua et al., Cell 94:261-271 (1998). The ETR1 gene encodes an ethylene receptor, as indicated by the ethylene-binding activity of its amino-terminal domain. See Schalleret al., Science 270/1809-1811 (1995). The ETR2 gene products are cellular receptors involved in the development of different plant tissues. See Sakai et al., Proc. Natl. Acad. ScL U.S.A. 95(10):58U-M (1998). [291] G-Receptor Coupled Genes and Gene Products. G-receptor coupled receptors (GPCR) constitute another large superfamily of proteins that communicate signals across cell membrane. On the exterior side, they bind to a ligand (which could be a photon, hormone, antigen, growth factor or a neurotransmitter) and at the cytosolic side, they activate a GTP binding protein (G-protein). All GPCRs share one characteristic in that they consist of a single protein chain that crosses the cell membrane seven times. Loops that occur between the cell wall and the cell membrane take part in ligand recognition, while the second and third cytosolic loop and part of the C- terminal end of the receptors are implicated in G-protein recognition. [292] G proteins are characterized by three subunits: α, β and v. The α subunit has two domains. Of the two, the function of only one, namely, the ras domain is known in somewhat detail. It contains a GDP/GTP binding site. A covalently attached lipid attaches this subunit to the lipid cell membrane bilayer. After the formation of the ligand-receptor complex, GNRP (guanine nucleotide release protein) catalyzes the removal of GDP and replaces it with

GTP. Simultaneously, a subunit is dissociated from the β and Y subunits. Both the GTP-bound subunit and free subunits can activate downstream effectors. Such effectors include adenyl cyclase and ion channels. The cycle returns by the intrinsic GTPase activity of the α-subunit. It hydrolyzes GTP into GDP concomitant with reassociation of the α-subunit with the β and v subunits.

[293] GPCR is highly expressed in meristemic tissues. See Colucci et al., Proc. Nat'l Acad. Sci. U.S.A. 99:4736-41 (2002). GPCR overexpression in Arabidopsis results in loss of seed dormancy and shortening of time to flower and fruit set. Overexpression has been shown to lead to excessive cell division in meristem and initiation of additional meristems. [294] Antisense suppression of GCR1 in Arabidopsis results in a phenotype suggestive of a role in cytokinin signaling. See Hooley et al., Lond. B. Biol. Sci. 353:1425-30 (1998). Furthermore, transgenic Arabidopsis expression antisense GDR1 under the control of constitutive cauliflower mosaic virus 35S promoter show reduced sensitivity to cytokinins in roots and shoots, but respond normally to other plant hormones. This suggests a role for GCR1 in cytokinin signal transduction. Plakidou-Dymock et al., Curr. Biol. 12:215-24 (1998).

3. Intracellular Transducer Genes and Gene Products

[295] Cell signaling genes and gene products also can be intracellular transducers along the signaling cascade. One intracellular transducer, the Mago nashi protein, has been studied extensively in Drosophila. See Newmark et al., Development 124(16):3197-207 (1997). Mago nashi gene products mediate the polarity of the developing Drosophila ooctye. A mago nashi gene analog has been found in rice. See Swidzinski et al., Genome 44(3J:394-400 (2001). Mago nashi gene products were found to be expressed in root, leaf and developing seed tissue as determined by RNA and protein gel blot analysis.

[296] Receptor kinases are also important cell signaling genes. The Ras superfamily of monomeric GTPases comprises Ras, Rab, and Rho/Rac. Ras

and Rac relay signals from surface receptors to actin cytoskeleton. Members of Rab are involved in regulating intracellular membrane vesicle traffic. Ras proteins, which are located on inner surface of the membrane, are involved in initiating the kinase cascade that communicates signals from the receptor to the nucleus.

[297] RAB exhibits high degree of functional and structural conservation in all eukaryotic cells studied. Haizel et al., Plant Physiol. 108:59-67 (1995). Rab GTPases are a large family of the small GTP-binding protein superfamily. Vernoud, et al., Plant Physiol. 737:1191 (2003). Rab has been shown to have a role in intracellular membrane trafficking and to be involved in membrane fusion events. Rab is also thought to be involved in intracellular transport from the ER to Golgi apparatus. Bown and Gatehouse, Plant MoI. Biol. 27:1195-99 (1993).

[298] Rab GTPases cycle between inactive GDP-bound form located in cytosol and active GTP-bound form which is membrane associate. Upon binding to target membrane, the RAB GTPase is converted from GDP-bound form the GTP bound form through activation by RABGEF proteins. The intrinsic activity of monomeric GTP-binding proteins is very low. GAPs can modulate the cellular activity of these proteins by several orders of magnitude. Haizel. GAPs bind at specific effector-binding domains. [299] Most GTP-binding mRNAs are constitutively expressed in similar amounts, RAB1 , RAB2, RAB5, RAB7 have elevated levels in root nodules, while certain RAB7, RAB8, and RAB11 are enriched in aerial parts of the plant suggesting that most small GTPases have housekeeping functions whereas a few are required for specialized activities that are important to specialized cells. See Borg et al., Plant J. 77:237-50 (1997). [300] The RAB11 protein is known to also possess regions which participate in GTP binding and hydrolysis. A c-terminal CCXX motif, essential for membrane attachment, is conserved in RAB11. Haizel et al., Plant Physiol. 708:59-67 (1995).

[301] RAB5 is associated with early endosomes. See Haizel et al., supra. In vitro assays demonstrated that RAB5 controls early endosome fusion and plays a critical role in trafficking soluble cargoes from prevacuolar compartment to central vacuole during early endocytosis. See Gorvel et al. Cell 64:915-25; Sohn et al., Plant Cell 75:1057 (2003); Daitoku et al., Int. J. MoI. Med. 8:397 (2001).

[302] RAB7 affects the transport of cargo from early endosomes to late endosomes and lysosomes. See Feng et al., J. Cell Biol. 737:1435-52 (1995); Mukhopadhyay et al., J. Biol. Chem. 272:13055-59 (1997). In plants, RAB7 is localized in late endosomes. Additionally, RAB7 has a conserved effector domain, YKATIGADF. RAB7 has a c-terminal motif that differs from RAB 11 (CXC motif). Haizel et al., supra.

[303] Ras-related nuclear protein (RAN) is a 25 kDa nuclear GTP-binding protein with a highly conserved amino acid sequence among plants, animals and fungi. Ach and Gruissem, Proc. Nat'l Acad. Sci. U.S.A. 91:5863-7 (1994). Ran complexes with chromatin-associated protein RCC1 , a negative regulator of mitosis. Ran is thought to function in a GTPase switch involved in the coupling of the completion of DNA replication to onset of M phase. The role of Ran is thought to be broader, however, than regulation of mitosis only. For example, in tomato, Ran has been shown to be constitutively expressed in all tissues, regardless of the stage of cell cycle. Furthermore, the levels of tomato Ran mRNA do not change during fruit development. In interphase cells, RAN GTPases direct nucleocytoplasmic transport. Like other GTPases, RAN cycles between GDP and GTP bound states. However for RAN, GTP binding and hydrolysis is linked to transport into or out of the nucleus. Unlike other GTPases, RAN is not post-translationally lipid modified and does not associate with cellular membranes. Vernoud et al., supra at 1203. [304] Ras GTPases are shown to regulate cell proliferation in yeast and mammalian systems. Vernoud, et al., Plant Physiol. 737:1191 (2003). This group includes the Rho GTPases. The Rho GTPases are involved in assembly of actin cytoskeleton. Haizel et al., supra. Ras, however, has not

yet been identified in plants. Instead, the Ras homologs RAB and RHO have been characterized. Functionally, Ras is activated by the release of GDP. The binding of GTP begins a cascade event. Ras recruits and then binds Raf. The binding of Ras to Raf initiates a phosphorylation cascade called the MAPK cascade. The ethylene receptor ETR1 , is thought to pass its signal to CTR1 , a protein kinase of the Raf family. In the context of the phosphorylation cascade, Raf is referred to as MAP kinase kinase kinase (MAPKKK). MAPKKK phosphorylates MAPKK which phosphorylates MAPK. MAPK enters the nucleus where it activates other protein kinases, transcription factors, and regulatory proteins.

[305] Three types of receptor-like kinases are known in plants. S receptor kinases have an S domain which consists of 10 cysteins in a particular arrangement with other amino acids. SRK genes are expressed predominantly in pistols. Leucine rich repeat receptors possess a beta-sheet with an exposed face that participates in protein-protein interactions. These proteins are involved in disease resistance by recognition of ligands produced by pathogens and the subsequent activation of intracellular defense response. See Bent et al., Plant Cell 8:1757:71 (1996)). S receptor kinases are also involved in the normal development of plants.

[306] At least one class of intracellular transducers, 14-3-3 proteins, function as regulators of a wide range of biological processes. One feature of 14-3-3 proteins is their ability to bind a multitude of functionally diverse signaling proteins, including kinases, phosphatases, and transmembrane receptors. 14-3-3 proteins interact directly with different target proteins. Typically the target protein is phosphorylated, enabling binding of 14-3-3 to the target protein, altering its activity. 14-3-3 binding can is known to directly alter protein activity (either positively or negatively), control nuclear-cytoplasmic shuttling, mediate protein import into mitochondria and chloroplasts, and form a scaffold to permit interactions between two different binding proteins. 14-3- 3 proteins are also known to be involved in cell signaling. For example, response to plant pathogens involve 14-3-3 proteins and calmodulin-domain

protein kinases (CDPK), MAP kinase pathways, lipoxygenases and ion channels have been identified as potential targets for 14-3-3 proteins important in defense.

[307] The sequences of the invention encode proteins involved in cell signaling. These proteins include 14-3-3 protein, 1-aminocyclopropane-1- carboxylate synthase, 1-aminocyclopropane-i-carboxylate oxidase, cyclin- dependant kinase inhibitor, cytokinin oxidase, ethylene receptor, ethylene- responsive elongation factor (EF-TS), F-box family protein, G protein-coupled receptor, GA20-oxidase, giberellic acid insensitive (GAI), gibberellin 2- oxidase, indole-3-acetaldehyde reductase, indole-3-acetonitrilase, Mago Nashi protein, MAP kinase, MAP kinase kinase, MAP kinase kinase kinase, polyphosphoinositide binding protein SSH2P, RAB11G, RAB11J, RAB5B, RAB7, RAN (GTPase activating protein), RAS-like GTP-binding protein, SNF1 -related protein kinase, steroid reductase, steroid sulfotransferase, and synaptobrevin-like protein. As discussed in more detail below, manipulation of the expression of the cell signaling genes and polynucleotides, or manipulation of the activity of the encoded proteins and polypeptides, can result in a transgenic plant with a desired phenotype that differs from the phenotype of a wild-type plant of the same species.

[308] Throughout this description, reference is made to cell signaling gene products. As used herein, a "cell signaling gene product" is a product encoded by a cell signaling gene, and includes both nucleotide products, such as RNA, and amino acid products, such as proteins and polypeptides. Examples of specific cell signaling genes of the invention include SEQ ID NOs: 1-197. Examples of specific cell signaling gene products of the invention include products encoded by any one of SEQ ID NOs: 198-583. Reference also is made herein to cell signaling proteins and cell signaling polypeptides. Examples of specific cell signaling proteins and polypeptides of the invention include polypeptides encoded by any of SEQ ID NOs: 1-197 or polypeptides comprising the amino acid sequence of any of SEQ ID NOs: 198-394.

[309] The present invention also includes sequences that are complements, reverse sequences, or reverse complements to the nucleotide sequences disclosed herein.

[310] The present invention also includes conservative variants of the sequences disclosed herein. The term "variant," as used herein, refers to a nucleotide or amino acid sequence that differs in one or more nucleotide bases or amino acid residues from the reference sequence of which it is a variant.

[311] Thus, in one aspect, the invention includes conservative variant polynucleotides. As used herein, the term "conservative variant polynucleotide" refers to a polynucleotide that hybridizes under stringent conditions to an oligonucleotide probe that, under comparable conditions, binds to the reference gene the conservative variant is a variant of. Thus, for example, a conservative variant of SEQ ID NO: 1 hybridizes under stringent conditions to an oligonucleotide probe that, under comparable conditions, binds to SEQ ID NO: 1. For example, sequences are considered to hybridize when they form a double-stranded complex in a hybridization solution of 6X SSC, 0.5% SDS, 5X Denhardt's solution and 100μg of non-specific carrier DNA. See F. M. Ausubel et al. (Eds.), Current Protocols in Molecular Biology, John Wiley & Sons, New York, NY (2002). "Moderate stringency" is defined as a temperature of 60 0 C in a hybridization solution of 6X SSC, 0.5% SDS, 5X Denhardt's solution and 100μg of non-specific carrier DNA. Id. "High stringency" hybridization conditions are, for example, 68 0 C in a hybridization solution of 6X SSC, 0.5% SDS, 5X Denhardt's solution and 100μg of nonspecific carrier DNA. Id. Following the moderate stringency hybridization reaction, the nucleotides are washed in a solution of 2X SSC plus 0.05% SDS for five times at room temperature, with subsequent washes with 0.1 X SSC plus 0.1 % SDS at 60 0 C for 1 h.

[312] One aspect of the invention provides conservative variant polynucleotides that exhibit at least about 75% sequence identity to their respective reference sequences. "Sequence identity" has an art-recognized

meaning and can be calculated using published techniques. See Computational Molecular Biology, Lesk, ed. (Oxford University Press, 1988), Biocomputing: Informatics And Genome Projects. Smith, ed. (Academic Press, 1993), Computer Analysis Qf Sequence Data, Part I. Griffin & Griffin, eds., (Humana Press, 1994), Sequence Analysis In Molecular Biology, Von Heinje ed., Academic Press (1987), Sequence Analysis Primer, Gribskov & Devereux, eds. (Macmillan Stockton Press, 1991), Gish et al., J. MoI. Biol. 215: 403 (1990); Gish and States, Nature Genet. 3: 266 (1993); Madden et al., Meth. Enzymol. 266:131 (1996); Altschul et al., Nucleic Acids Res. 25: 3389 (1997); and Zhang and Madden, Genome Res. 7: 649-656 (1997), and Carillo and Lipton, SIAM J. Applied Math. 48: 1073 (1988). Methods commonly employed to determine identity or similarity between two sequences include but are not limited to those disclosed in Guide To Huge Computers, Bishop, ed., (Academic Press, 1994) and Carillo & Lipton, supra. [313] Methods to determine identity and similarity are codified in computer programs. Preferred computer program methods to determine identity and similarity between two sequences include but are not limited to the GCG program package (Devereux et al., Nucleic Acids Research 12: 387 (1984)), BLASTP, BLASTN, FASTA (Atschul et al., J. MoI. Biol 215: 403 (1990)), and FASTDB (Brutlag et al., Comp. App. Biosci. 6: 237 (1990)). [314] The invention includes conservative variant polynucleotides having a sequence identity that is greater than or equal to 99%, 98%, 97%, 96%, 95%, 94%, 93%, 92%, 91%, 90%, 89%, 88%, 87%, 86%, 85%, 84%, 83%, 82%, 81 %, 80%, 79%, 78%, 77%, 76%, 75%, 74%, 73%, 72%, 71 %, 70%, 69%, 68%, 67%, 66%, 65%, 64%, 63%, 62%, 61 %, or 60% to any one of 1-29. In such variants, differences between the variant and the reference sequence can occur at the 5' or 3' terminal positions of the reference nucleotide sequence or anywhere between those terminal positions, interspersed either individually among nucleotides in the reference sequence or in one or more contiguous groups within the reference sequence.

[315] Additional conservative variant polynucleotides contemplated by and encompassed within the present invention include polynucleotides comprising sequences that differ from the polynucleotide sequences of SEQ ID NOs: 1- 197 or complements, reverse complements or reverse sequences thereof, as a result of deletions and/or insertions totaling less than 30% of the total sequence length. In one embodiment, deletions and/or insertions total less than 20% or less than 10% of the total length.

[316] The invention also includes conservative variant polynucleotides that, in addition to sharing a high degree of similarity in their primary structure (sequence) to SEQ ID NOs have at least one of the following features: (i) they contain an open reading frame or partial open reading frame encoding a polypeptide having substantially the same functional properties in polynucleotide synthesis as the polypeptide encoded by the reference polynucleotide, or (ii) they have nucleotide domains or encoded protein domains in common. The invention includes conservative variants of SEQ ID NOs: 1-197 that encode proteins having the enzyme or biological activity or binding properties of the protein encoded by the reference polynucleotide. Such conservative variants are functional variants, in that they have the enzymatic or binding activity of the protein encoded by the reference polynucleotide.

[317] In accordance with the invention, polynucleotide variants can include a "shuffled gene" such as those described in e.g. U.S. Patent Nos. 6,500,639, 6,500,617, 6,436,675, 6,379,964, 6,352,859, 6,335,198, 6,326,204 and 6,287,862. A variant of a nucleotide sequence of the present invention also can be a polynucleotide modified as disclosed in U.S. Patent No. 6,132,970, which is incorporated herein by reference.

[318] In accordance with one embodiment, the invention provides a polynucleotide that encodes a cell signaling protein such as 14-3-3 protein, 1- aminocyclopropane-1-carboxylate synthase, 1-aminocyclopropane-1- carboxylate oxidase, cyclin-dependant kinase inhibitor, cytokinin oxidase, ethylene receptor, ethylene-responsive elongation factor (EF-TS), F-box

family protein, G protein-coupled receptor, GA20-oxidase, giberellic acid insensitive (GAI), gibberellin 2-oxidase, indole-3-acetaldehyde reductase, indole-3-acetonitrilase, Mago Nashi protein, MAP kinase, MAP kinase kinase, MAP kinase kinase kinase, polyphosphoinositide binding protein SSH2P, RAB11G, RAB11J, RAB5B, RAB7, RAN (GTPase activating protein), RAS- like GTP-binding protein, SNF1 -related protein kinase, steroid reductase, steroid sulfotransferase, and synaptobrevin-like protein. SEQ ID NOs: 1-197 provide examples of such polynucleotides.

[319] In accordance with another embodiment, a polynucleotide of the invention encodes the catalytic or protein binding domain of a polypeptide encoded by any of SEQ ID NOs: 1-197 or of a polypeptide comprising any of SEQ ID NOs: 198-394. The catalytic and protein binding domains of the polysaccharide synthesis proteins of the invention are known in the art. The conserved sequences of these proteins are shown in FIGURES 1-197 as underlined text.

[320] The invention also encompasses as conservative variant polynucleotides that differ from the sequences discussed above but that, as a consequence of the degeneracy of the genetic code, encode a polypeptide which is the same as that encoded by a polynucleotide of the present invention. The invention also includes as conservative variants polynucleotides comprising sequences that differ from the polynucleotide sequences discussed above as a result of substitutions that do not affect the amino acid sequence of the encoded polypeptide sequence, or that result in conservative substitutions in the encoded polypeptide sequence. [321] The present invention also includes an isolated polypeptide encoded by a polynucleotide comprising any of SEQ ID NOs: 1-197 or any of the conservative variants thereof discussed above. The invention also includes polypeptides comprising SEQ ID NOs: 198-394 and conservative variants of these polypeptides.

[322] In accordance with the invention, a variant polypeptide or protein refers to an amino acid sequence that is altered by the addition, deletion or substitution of one or more amino acids.

[323] The invention includes conservative variant polypeptides. As used herein, the term "conservative variant polypeptide" refers to a polypeptide that has similar structural, chemical or biological properties to the protein it is a conservative variant of. Guidance in determining which amino acid residues can be substituted, inserted, or deleted can be found using computer programs well known in the art such as Vector NTI Suite (InforMax, MD) software. In one embodiment of the invention, conservative variant polypeptides that exhibit at least about 75% sequence identity to their respective reference sequences.

[324] Conservative variant protein includes an "isoform" or "analog" of the polypeptide. Polypeptide isoforms and analogs refers to proteins having the same physical and physiological properties and the same biological function, but whose amino acid sequences differs by one or more amino acids or whose sequence includes a non-natural amino acid.

[325] Polypeptides comprising sequences that differ from the polypeptide sequences of SEQ ID NO: 198-394 as a result of amino acid substitutions, insertions, and/or deletions totaling less than 10% of the total sequence length are contemplated by and encompassed within the present invention. [326] One aspect of the invention provides conservative variant polypeptides function in cell signaling, as determined by one or more appropriate assays, such as those described below. The invention includes variant polypeptides which are cell signaling or cell signaling-like proteins, such as those participating in the regulation of ethylene synthesis or those genes that encode a peptide having the biological activity of a receptor kinase. As discussed above, the invention includes variant polynucleotides that encode polypeptides that function as cell signaling proteins.

[327] In one embodiment, an isolated polynucleotide comprise a sequence encoding the catalytic or substrate-binding domain from a polypeptide

selected from any one of SEQ ID NO: 198-394. In one aspect, the polynucleotide encodes a polypeptide having the same or similar activity of a polypeptide selected from any one of SEQ ID NO: 198-394. [328] The activities and physical properties of cell signaling proteins can be examined using any method known in the art. The following examples of assay methods are not exhaustive and are included to provide some guidance in examining the activity and distinguishing protein characteristics of cell signaling protein variants. In any case, any and all biological, chemical, enzymatic or radiologic assay method can be used to determine whether a polypeptide has the same or similar activity of another polypeptide. [329] One such assay monitors DNA synthesis by thymidine incorporation. DNA synthesis correlated, in most cases, with cellular growth. It is monitored in, for example, tissue samples from transformed and control plants by pulse labeling with about 1 μCi of [methyl- 3 H]thymidine (Ambersham Pharmacia Biotech, Benelux, Roosendaal, The Netherlands) for about 30 minutes at about 28°C on a rotary shaker. Labeled cells can be collected by centrifugation and immediately frozen in liquid nitrogen. Total DNA and protein can be extracted by grinding and precipitated by standard techniques. Once collected, protein content can be measured using, for example, Bradford reagent (Bio-Rad Laboratories, Hercules, CA) or other techniques. Likewise, a protein sample can by hydrolyzed and incorporated radioactivity measured by scintillation counting. Upon quenching correction, total DNA synthesis can be expressed as Bq per μg of protein in the sample. DNA synthesis can also be measured, for example, using the flow cytometrical analysis of nuclei. See, e.g., Porceddu et al., J. Biol. Qhem. 276(39):36354- 360 (2001).

[330] Biological assays using transgenic plants can indicate whether a putative cell signaling gene possesses a specific activity. For example, gibberellin-mutants tend to possess striking phenotypes. See Pend and Harberd, Plant Physiol. 773:1051-1058 (1997). Transgenic plants transformed with DNA constructs expressing a putative gibberellic acid

insensitive (GAI) gene product, therefore, would be expected exhibit a distinctive GAI phenotype.

[331] Phytohormone concentrations can also be measured. For example, gibberellin and abscisic acid content of transgenic and control plants can be measured using the technique of Green et al., Plant Physiol. 11 '4(1 r J:203-212 (1997). Briefly, tissue samples are extracted, purified and analyzed by GC- MS for gibberellins and abscisic acid. GC-MS permits the monitoring of characteristic ions corresponding to biologically gibberellins and biologically inactive gibberellins.

[332] GA20-oxidase activity can be measured in protein extracts by the technique of Xu et al., Proc. Natl. Acad. ScL USA 92(14):6640-6644 (1995). Briefly, extracts are concentrated and used to assay the oxidation of the substrates [ 14 C]GA 53 and [ 14 C]GAig. The products of the assay are separated using HPLC, collected and again purified by reverse-phase HPLC. The samples are then analyzed by GC-MS.

[333] Likewise, the inactivation of bioactive GA by GA 2-oxidase can be monitored by the technique of Ross et al., Plant J. 7:513-523 (1995). [334] In addition to biological assays using transgenic plants, brassionosteriods response genes and gene products can be measured. For example, a putative steroid sulfotransferase can be assayed using the technique of Rouleau et al., J. Biol. Chem. 274(30):20925-30 (1999). Briefly, a purified, recombinant gene product is tested for the ability to transfer the 35 S-labeled sulfonate group from the cosubstrate PAPS (NEN Life Science Products) to brassionosteriods.

[335] Additionally, a functional assay measuring steroid 5α-reductase activity has been described. See Li et al., Proc. Natl. Acad. ScL USA 94:3554-3559 (1997). Briefly, the activity of recombinantly expressed steroid 5α-reductase proteins is measured by the reduction of radiolabeled progesterone to 4,5- dihydroprogesterone. Alternative radiolabeled substrates can be used. [336] Cytokinins can be measured directly by extraction from plant tissue and purification by HPLC. See Smart et al., Plant Cell 3:647-656 (1991).

Cytokinin oxidases/dehydrogenases can be measured by the degradation of the cytokinins isopentenyladenine, zeatin, and their ribosides by oxidative side chain cleavage (for a review see Schmulling et al., J. Plant Res. 116(3):241- 52 (2003). Likewise, activity can be inferred from interation of proteins with the cyclases/histidine kinases associated sensory extracellular domain of the CRE1/WOL/AHK4, AHK2, and AHK3 cellular receptors. [337] In the case of auxin response gene products, the activity of putative nitrolases can be determined by the technique of Nagasawa et al., Eur. J. Biochem. 194:765-772 (1990), using either thiophene-2-acetonitrile or indole- 3-acetonitrile as a substrate.

[338] Protein kinase acitivty can, for example, be measured by quantifying the amount of ATP remaining in solution following a kinase reaction. The kinase gene product is purified using standard techniques and combined with its substrate to form a kinase reaction. A non-radioactive assay is performed in a single well of a 96- or 384-well plate by adding a volume of luciferase reagent (Kinase-Glo™ Reagent, Promega Corporation, Madison Wl) equal to the volume of solution in the well of a completed kinase reaction. Subsequently, luminescence is measured by a luminomiter. The luminescent signal is correlated with the amount of ATP and inversely correlated with the amount of kinase activity. This assay can be performed with virtually any kinase and substrate combination. The kinase substrate can be a peptide, protein or lipid. Additionally, radiologic methods for detecting kinase reactions are well known.

[339] Likewise, putative SNF1 -related protein kinases can, for example, be assayed using the methods of Huang and Huber, Plant Cell Physiol. 42(10): 1079-87 (2001).

[340] Putative G-coupled proteins can be verified by their ability to bind G- proteins. Briefly, putative G-coupled proteins are expressed as glutathione S- transferase fusion proteins and purified using glutathione-agarose beads. G protein subunits (Gj 3 , Gj 2 , and G 0 ) from the desired plant species are recombinantly generated and labeled with [ 35 S]methionine by in vitro

translation. Glutathione S-transferase or recombinant G-coupled proteins proteins are incubated separately with G-proteins which are preincubated with necessary cofactors.. The total input of each of the labeled G-protein can be resolved on SDS-PAGE gels stained with Coomassie Brilliant Blue, together with protein samples eluted from the binding assays. Some G-coupled protein activity can also be monitored, for example, through the activation of phospholipase C. See, e.g., Ghosh and Smrcka, Methods MoI. Biol. 237:67- 75 (2004). Phospholipase C activity can also be measured on microsomal membrane preparations, according to the method described by Zhang et al., Planta 275:312-318 (2002)

[341] Small GTP-binding proteins encoded by the Rab and Ran gene families can be monitored using GTP-binding assays or GAP assays. Briefly, GAP assays, filter-binding assays, and the loading small GTP-binding proteins with 5'-[γ 32 P]GTP can be done according to the method of Strom et al., Nature 361:736-739 (1993). For the analysis of reaction products by TLC, small GTP-binding proteins can be loaded with 5'-[α 32 P]GTP and purified by passage through Bio-Spin 6 chromatography columns (Bio-Rad). A GAP assay mixture can be analyzed by TLC. Aliquots can be spotted onto polyethyleneimine cellulose foils, and the chromatogram developed. The reaction products or the applied GTP and GDP standard can be visualized by autoradiography or by UV light, respectively.

B. Methods of Using Cell Signaling Genes, Polynucleotide and

Polypeptide Sequences

[342] The present invention provides methods of using cell signaling genes and conservative variants thereof. The invention includes methods and constructs for altering expression of cell signaling or cell signaling-like genes and/or gene products for purposes including, but not limited to (i) investigating the gene or gene product role in a cell signaling pathway and its ultimate effect on plant phenotype and (ii) to effect a change in plant phenotype. For example, the invention includes methods and tools for modifying wood quality, fiber development, wood lignin and polysaccharide content, fruit ripening, and

plant growth and yield by altering expression of one or more cell signaling genes.

[343] The invention comprises methods of altering the expression of any of the polysaccharide synthesis genes and variants discussed above. Thus, for example, the invention comprises altering expression of a cell signaling gene present in the genome of a wild-type plant of a species of Eucalyptus or Pinus. In one embodiment, the cell signaling gene comprises a nucleotide sequence selected from SEQ ID NOs: 1-197 sequences or the conservative variants thereof, as discussed above.

1. Techniques to Alter Gene Expression

[344] Techniques which can be employed in accordance with the present invention to alter gene expression, include, but are not limited to: (i) over- expressing a gene product, (ii) disrupting a gene's transcript, such as disrupting a gene's mRNA transcript; (iii) disrupting the function of a polypeptide encoded by a gene, or (iv) disrupting the gene itself. Over- expression of a gene product, the use of antisense RNAs, ribozymes, and the use of double-stranded RNA interference (dsRNAi) are valuable techniques for discovering the functional effects of a gene and for generating plants with a phenotype that is different from a wild-type plant of the same species. [345] Over-expression of a target gene often is accomplished by cloning the gene or cDNA into an expression vector and introducing the vector into recipient cells. Alternatively, over-expression can be accomplished by introducing exogenous promoters into cells to drive expression of genes residing in the genome. The effect of over-expression of a given gene on cell function, biochemical and/or physiological properties can then be evaluated by comparing plants transformed to over-express the gene to plants that have not been transformed to over-express the gene.

[346] Antisense RNA, ribozyme, and dsRNAi technologies typically target RNA transcripts of genes, usually mRNA. Antisense RNA technology involves expressing in, or introducing into, a cell an RNA molecule (or RNA derivative) that is complementary to, or antisense to, sequences found in a

particular mRNA in a cell. By associating with the mRNA, the antisense RNA can inhibit translation of the encoded gene product. The use of antisense technology to reduce or inhibit the expression of specific plant genes has been described, for example in European Patent Publication No. 271988, Smith et al., Nature, 334:724-726 (1988); Smith et. al., Plant MoI. Biol., 14:369-379 (1990)).

[347] A ribozyme is an RNA that has both a catalytic domain and a sequence that is complementary to a particular mRNA. The ribozyme functions by associating with the mRNA (through the complementary domain of the ribozyme) and then cleaving (degrading) the message using the catalytic domain.

[348] RNA interference (RNAi) involves a post-transcriptional gene silencing (PTGS) regulatory process, in which the steady-state level of a specific mRNA is reduced by sequence-specific degradation of the transcribed, usually fully processed mRNA without an alteration in the rate of de novo transcription of the target gene itself. The RNAi technique is discussed, for example, in Elibashir, et al., Methods Enzymol. 26:199 (2002); McManus & Sharp, Nature Rev. Genetics 3:737 (2002); PCT application WO 01/75164; Martinez et al., Cell 110:563 (2002); Elbashir et al., supra; Lagos-Quintana et al., Curr. Biol. 12:735 (2002); Tuschl et al., Nature Biotechnol. 20:446 (2002); Tuschl, Chembiochem. 2:239 (2001); Harborth et al., J. Cell Sci. 114:4557 (2001); et al., EMBO J. 20:6877 (2001); Lagos-Quintana et al., Science 294:8538 (2001); Hutvagner et al., loc cit, 834; Elbashir et al., Nature 411:494 (2001). 2. DNA Constructs

[349] The present invention provides a DNA construct comprising at least one polynucleotide of SEQ ID NOs: 1-197 or conservative variants thereof, such as the conservative variants discussed above. Any method known in the art can be used to generate the DNA constructs of the present invention. See, e.g., Sambrook et al., supra.

[350] The invention includes DNA constructs that optionally comprise a promoter. Any suitable promoter known in the art can be used. A promoter is

a nucleic acid, preferably DNA, that binds RNA polymerase and/or other transcription regulatory elements. As with any promoter, the promoters of the invention facilitate or control the transcription of DNA or RNA to generate an mRNA molecule from a nucleic acid molecule that is operably linked to the promoter. The RNA can encode a protein or polypeptide or can encode an antisense RNA molecule or a molecule useful in RNAi. Promoters useful in the invention include constitutive promoters, inducible promoters, temporally regulated promoters and tissue-preferred promoters.

[351] Examples of useful constitutive plant promoters include: the cauliflower mosaic virus (CaMV) 35S promoter, which confers constitutive, high-level expression in most plant tissues (Odel et al., Nature 373:810(1985)); the nopaline synthase promoter (An et al., Plant Physiol. 88:547 (1988)); and the octopine synthase promoter (Fromm et al., Plant Cell 1:977 (1989)). It should be noted that, although the CaMV 35S promoter is commonly referred to as a constitutive promoter, some tissue preference can be seen. The use of CaMV 35S is envisioned by the present invention, regardless of any tissue preference which may be exhibited during use in the present invention. [352] Inducible promoters regulate gene expression in response to environmental, hormonal, or chemical signals. Examples of hormone inducible promoters include auxin-inducible promoters (Baumann et al., Plant Cell 17:323-334(1999)), cytokinin-inducible promoters (Guevara-Garcia, Plant MoI. Biol. 38:743-753(1998)), and gibberellin-responsive promoters (Shi et al. Plant MoI. Biol. 38:1053-1060(1998)). Additionally, promoters responsive to heat, light, wounding, pathogen resistance, and chemicals such as methyl jasmonate or salicylic acid, can be used in the DNA constructs and methods of the present invention.

[353] Tissue-preferred promoters allow for preferred expression of polynucleotides of the invention in certain plant tissue. Tissue-preferred promoters are also useful for directing the expression of antisense RNA or iRNA in certain plant tissues, which can be useful for inhibiting or completely blocking the expression of targeted genes as discussed above. As used

herein, vascular plant tissue refers to xylem, phloem or vascular cambium tissue. Other preferred tissue includes apical meristem, root, seed, and flower. In one aspect, the tissue-preferred promoters of the invention are either "xylem-preferred," "cambium-preferred" or "phloem-preferred," and preferentially direct expression of an operably linked nucleic acid sequence in the xylem, cambium or phloem, respectively. In another aspect, the DNA constructs of the invention comprise promoters that are tissue-specific for xylem, cambium or phloem, wherein the promoters are only active in the xylem, cambium or phloem.

[354] A vascular-preferred promoter is preferentially active in any of the xylem, phloem or cambium tissues, or in at least two of the three tissue types. A vascular-specific promoter is specifically active in any of the xylem, phloem or cambium, or in at least two of the three. In other words, the promoters are only active in the xylem, cambium or phloem tissue of plants. Note, however, that because of solute transport in plants, a product that is specifically or preferentially expressed in a tissue may be found elsewhere in the plant after expression has occurred.

[355] Additionally, the promoters of particular cell signaling genes may be expressed only within the cambium in developing secondary vasculature. Within the cambium, particular polysaccharide synthesis gene promoters may be expressed exclusively in the stem or in the root. Moreover, the cell signaling promoters may be expressed only in the spring or only in the summer, fall or winter.

[356] A promoter may be operably linked to the polynucleotide. As used in this context, operably linked refers to linking a polynucleotide encoding a structural gene to a promoter such that the promoter controls transcription of the structural gene. If the desired polynucleotide comprises a sequence encoding a protein product, the coding region can be operably linked to regulatory elements, such as to a promoter and a terminator, that bring about expression of an associated messenger RNA transcript and/or a protein product encoded by the desired polynucleotide. In this instance, the

polynucleotide is operably linked in the 5'- to 3'- orientation to a promoter and, optionally, a terminator sequence.

[357] Alternatively, the invention provides DNA constructs comprising a polynucleotide in an "antisense" orientation, the transcription of which produces nucleic acids that can form secondary structures that affect expression of an endogenous cell signaling gene in the plant cell. In another variation, the DNA construct may comprise a polynucleotide that yields a double-stranded RNA product upon transcription that initiates RNA interference of a cell signaling gene with which the polynucleotide is associated. A polynucleotide of the present invention can be positioned within a t-DNA, such that the left and right t-DNA border sequences flank or are on either side of the polynucleotide.

[358] It should be understood that the invention includes DNA constructs comprising one or more of any of the polynucleotides discussed above. Thus, for example, a construct may comprise a t-DNA comprising one, two, three, four, five, six, seven, eight, nine, ten, or more polynucleotides. [359] The invention also includes DNA constructs comprising a promoter that includes one or more regulatory elements. Alternatively, the invention includes DNA constructs comprising a regulatory element that is separate from a promoter. Regulatory elements confer a number of important characteristics upon a promoter region. Some elements bind transcription factors that enhance the rate of transcription of the operably linked nucleic acid. Other elements bind repressors that inhibit transcription activity. The effect of transcription factors on promoter activity can determine whether the promoter activity is high or low, i.e. whether the promoter is "strong" or "weak." [360] A DNA construct of the invention can include a nucleotide sequence that serves as a selectable marker useful in identifying and selecting transformed plant cells or plants. Examples of such markers include, but are not limited to, a neomycin phosphotransferase (nptll) gene (Potrykus et al., MoI. Gen. Genet. 799:183-188 (1985)), which confers kanamycin resistance. Cells expressing the nptll gene can be selected using an appropriate

antibiotic such as kanamycin or G418. Other commonly used selectable markers include a mutant EPSP synthase gene (Hinchee et a!., BioTechnology 6:915-922 (1988)), which confers glyphosate resistance; and a mutant acetolactate synthase gene (ALS), which confers imidazolinone or sulphonylurea resistance (European Patent Application No. 154,204). [361] The present invention also includes vectors comprising the DNA constructs discussed above. The vectors can include an origin of replication (replicons) for a particular host cell. Various prokaryotic replicons are known to those skilled in the art, and function to direct autonomous replication and maintenance of a recombinant molecule in a prokaryotic host cell. [362] For example, pMON530 is an Agrobacterium-based plant transformation vector for use in transformation of dicotyledonous plants is plasmid vector (Rogers et al., Improved vectors for plant transformation: expression cassette vectors and new selectable markers, in Recombinant DNA Methodology, Wu et al. (Ed.), Academic Press, San Diego, CA (1989). Another useful plasmid is pMON530, a derivative of pMON505, prepared by transferring the 2.3 kb Stul-Hindlll fragment of pMON316 into pMON526. Plasmid pMON526 is a simple derivative of pMON505 in which the Smal site is removed by digestion with Xmal, treatment with Klenow polymerase and ligation. Plasmid pMON530 retains all the properties of pMON505 and the CaMV35S-NOS expression cassette, but contains a unique cleavage site for Smal between the promoter and polyadenylation signal. [363] Binary vector pMON505 is a derivative of pMON200 (Rogers et al., supra) in which the Ti plasmid homology region, LIH, is replaced with a 3.8 kb Hindlll to Smal segment of the mini RK2 plasmid, pTJS75 (Schmidhauser and Helinski, J. Bacteriol. 164(1 ):446-55 (1985)). This segment contains the RK2 origin of replication, oriV, and the origin of transfer, oriT, for conjugation into Agrobacterium using the tri-parental mating procedure. Horsch and Klee., Proc. Natl. Acad. ScL U.S.A. 83:4428 (1986). Plasmid pMON505 retains all the important features of pMON200 including the synthetic multi-linker for insertion of desired DNA fragments, the chimeric NOS/NPTII'/NOS gene for

kanamycin resistance in plant cells, the spectinomycin/streptomycin resistance determinant for selection in E. coli and A. tumefaciens, an intact nopaline synthase gene for facile scoring of transformants and inheritance in progeny, and a pBR322 origin of replication for ease in making large amounts of the vector in E. coli. Plasmid pMON505 contains a single T-DNA border derived from the right end of the pTiT37 nopaline-type T-DNA. Southern blot analyses demonstrate that plasmid pMON505 and any DNA that it carries are integrated into the plant genome, that is, the entire plasmid is the T-DNA that is inserted into the plant genome. One end of the integrated DNA is located between the right border sequence and the nopaline synthase gene and the other end is between the border sequence and the pBR322 sequences. [364] A particularly useful Ti plasmid cassette vector is pMON 17227. This vector is described in WO 92/04449 and contains a gene encoding an enzyme conferring glyphosate resistance (denominated CP4), which is an excellent selection marker gene for many plants, including potato and tomato. The gene is fused to the Arabidopsis EPSPS chloroplast transit peptide (CTP2), and expression is driven by the promoter of choice. [365] In one embodiment, the DNA constructs comprise the polynucleotides pWVR8 or pART27 as described in Gleave, Plant MoI. Biol. 20:1203-27 (1992), or a fragment thereof. In another embodiment, the DNA constructs comprise any suitably modified Ti plasmid or a fragment thereof. [366] In one embodiment, the DNA constructs comprise at least one polynucleotide having any one of the sequences of SEQ ID NO: 1-197 and conservative variants thereof. In a further embodiment, the DNA constructs comprise a promoter such that the promoter is operably linked to the one or more polynuceotides. In another aspect, the promoter can be a constitutive promoter, a strong promoter, an inducible promoter, a regulatable promoter, a temporally regulated promoter, or a tissue-preferred promoter.

3. Transformed Host Cells, Plant Tissue and Plants

[367] The invention also provides host cells which are transformed with the DNA constructs of the invention. As used herein, a host cell refers to the cell

in which a polynucleotide of the invention is expressed. Accordingly, a host cell can be an individual cell, a cell culture or cells that are part of an organism. The host cell can also be a portion of an embryo, endosperm, sperm or egg cell, or a fertilized egg. In one aspect, the host cell is a plant cell. In another aspect, the plant cell is transformed with at least one polynucleotide selected from SEQ ID NO: 1-197.

[368] The present invention further provides transgenic plants comprising the DNA constructs of the invention. The invention includes transgenic plants that are angiosperms or gymnosperms. The DNA constructs of the present invention can be used to transform a variety of plants, both monocotyledonous (e.g. grasses, com, grains, oat, wheat and barley), dicotyledonous (e.g., Arabidopsis, tobacco, legumes, alfalfa, oaks, eucalyptus, maple), and Gymnosperms (e.g., Scots pine disclosed in Aronen et al., Tree Physiol. 15(1):65-70 (1995), white spruce disclosed in Ellis et al., Plant MoI. Biol. 77(%): 19-27(1991)), and larch (Huang et al., In Vitro Cell 27:201-207 (1991)).

[369] The plants also include turfgrass, wheat, maize, rice, sugar beet, potato, tomato, lettuce, carrot, strawberry, cassava, sweet potato, geranium, soybean, and various types of woody plants. Woody plants include trees such as palm oak, pine, maple, fir, apple, fig, plum and acacia. Woody plants also include rose and grape vines.

[370] In one embodiment, a transgenic plant is provided comprising at least one polynucleotide selected from SEQ ID NO: 1-197.

[371] In one embodiment, the DNA constructs of the invention are used to transform woody plants, i.e., trees or shrubs whose stems live for a number of years and increase in diameter each year by the addition of woody tissue. The invention includes methods of transforming plants including eucalyptus and pine species of significance in the commercial forestry industry such as plants selected from the group consisting of Eucalyptus grandis and its hybrids, and Pinus taeda, as well as the transformed plants and wood and wood pulp derived therefrom. Other examples of suitable plants include those

selected from the group consisting of Pinus banksiana, Pinus hrutia, Pinus caribaea, Pinus clausa, Pinus contorta, Pinus coulteri, Pinus echinata, Pinus eldarica, Pinus ellioti, Pinus jeffreyi, Pinus lambertiana, Pinus massoniana, Pinus monticola, Pinus nigra, Pinus palustris, Pinus pinaster, Pinus ponderosa, Pinus radiata, Pinus resinosa, Pinus rigida, Pinus serotina, Pinus strobis, Pinus sylvestris, Pinus taeda, Pinus virginiana, Abies amabilis, Abies balsamea, Abies concolor, Abies grandis, Abies lasiocarpa, Abies magnifica, Abies procera, Chamaecyparis lawsoniona, Chamaecyparis nootkatensis, Chamaecyparis thyoides, Juniperus virginiana, Larix decidua, Larix laricina, Larix leptolepis, Larix occidentalis, Larix siberica, Libocedrus decurrens, Picea abies, Picea engelmanni, Picea glauca, Picea mariana, Picea pungens, Picea rubens, Picea sitchensis, Pseudotsuga menziesii, Sequoia gigantea, Sequoia sempervirens, Taxodium distichum, Tsuga canadensis, Tsuga heterophylla, Tsuga mertensiana, Thuja occidentalis, Thuja plicata, Eucalyptus alba, Eucalyptus bancroftii, Eucalyptus botryoides, Eucalyptus bridgesiana, Eucalyptus calophylla, Eucalyptus camaldulensis, Eucalyptus citriodora, Eucalyptus cladocalyx, Eucalyptus coccifera, Eucalyptus curtisii, Eucalyptus dalrympleana, Eucalyptus deglupta, Eucalyptus delagatensis, Eucalyptus diversicolor, Eucalyptus dunnii, Eucalyptus ficifolia, Eucalyptus globulus, Eucalyptus gomphocephala, Eucalyptus gunnii, Eucalyptus henryi, Eucalyptus laevopinea, Eucalyptus macarthurii, Eucalyptus macrorhyncha, Eucalyptus maculata, Eucalyptus marginata, Eucalyptus megacarpa, Eucalyptus melliodora, Eucalyptus nicholii, Eucalyptus nitens, Eucalyptus nova-angelica, Eucalyptus obliqua, Eucalyptus occidentalis, Eucalyptus obtusiflora, Eucalyptus oreades, Eucalyptus pauciflora, Eucalyptus polybractea, Eucalyptus regnans, Eucalyptus resinifera, Eucalyptus robusta, Eucalyptus rudis, Eucalyptus saligna, Eucalyptus sideroxylon, Eucalyptus stuartiana, Eucalyptus tereticornis, Eucalyptus torelliana, Eucalyptus urnigera, Eucalyptus urophylla, Eucalyptus viminalis, Eucalyptus viridis, Eucalyptus wandoo, and Eucalyptus youmanni.

[372] As used herein, the term "plant" also is intended to include the fruit, seeds, flower, strobilus, etc. of the plant. A transformed plant of the current invention can be a direct transfectant, meaning that the DNA construct was introduced directly into the plant, such as through Agrobacterium, or the plant can be the progeny of a transfected plant. The second or subsequent generation plant can be produced by sexual reproduction, i.e., fertilization. Furthermore, the plant can be a gametophyte (haploid stage) or a sporophyte (diploid stage).

[373] As used herein, the term "plant tissue" encompasses any portion of a plant, including plant cells. Plant cells include suspension cultures, callus, embryos, meristematic regions, callus tissue, vascular tissue, apical meristem, vascular cambium, xylem, phloem, flower, leaves, roots, shoots, gametophytes, sporophytes, pollen, seeds and microspores. Plant tissues can be grown in liquid or solid culture, or in soil or suitable media in pots, greenhouses or fields. As used herein, "plant tissue" also refers to a clone of a plant, seed, progeny, or propagule, whether generated sexually or asexually, and descendents of any of these, such as cuttings, cone, fruit, and seeds.

[374] In accordance with one aspect of the invention, a transgenic plant that has been transformed with a DNA construct of the invention has a phenotype that is different from a plant that has not been transformed with the DNA construct.

[375] As used herein, "phenotype" refers to a distinguishing feature or characteristic of a plant which can be altered according to the present invention by integrating one or more DNA constructs of the invention into the genome of at least one plant cell of a plant. The DNA construct can confer a change in the phenotype of a transformed plant by modifying any one or more of a number of genetic, molecular, biochemical, physiological, morphological, or agronomic characteristics or properties of the transformed plant cell or plant as a whole.

[376] For example, gibberellic acid insensitive plants have characteristic phenotypes typified by dark green leaves and reduced stem elongation resulting in a dwarf growth habit. See Peng and Harberd, Plant Physiol. 773:1051-1058 (1997). Thus, plant stem cell growth can be modulated by altering the GA cell signaling cascade, its biosynthesis or degradation. Gene and gene products which catalyze each of these events can be used to increase or decrease plant stem cell growth. In this manner, the polynucleotides of the invention can be used to modulate GA cell signaling cascade, its biosynthesis or degradation, and thereby mediate plant growth. [377] In one embodiment, transformation of a plant with a DNA construct of the present invention can yield a phenotype including, but not limited to any one or more of increased drought tolerance, herbicide resistance, reduced or increased height, reduced or increased branching, enhanced cold and frost tolerance, improved vigor, enhanced color, enhanced health and nutritional characteristics, improved storage, enhanced yield, enhanced salt tolerance, enhanced resistance of the wood to decay, enhanced resistance to fungal diseases, altered attractiveness to insect pests enhanced heavy metal tolerance, increased disease tolerance, increased insect tolerance, increased water-stress tolerance, enhanced sweetness, improved texture, decreased phosphate content, increased germination, increased micronutrient uptake, improved starch composition, improved flower longevity, production of novel resins, increased or decreased cellulose content, increased or decreased lignin content, increased or decreased nonlignin cell wall phenolics and production of novel proteins or peptides.

[378] In another embodiment, the affected phenotype includes one or more of the following traits: propensity to form reaction wood, a reduced period of juvenility, an increased period of juvenility, self-abscising branches, accelerated reproductive development or delayed reproductive development, as compared to a plant of the same species that has not been transformed with the DNA construct.

[379] In a further embodiment, the phenotype that is different in the transgenic plant includes one or more of the following: lignin quality, lignin structure, wood composition, wood appearance, wood density, wood strength, wood stiffness, cellulose polymerization, fiber dimensions, lumen size, proportion of rays, proportion of vessel elements, other plant components, plant cell division, plant cell development, number of cells per unit area, cell size, cell shape, cell wall composition, rate of wood formation, aesthetic appearance of wood, formation of stem defects, average microfibril angle, width of the S2 cell wall layer, rate of growth, rate of root formation ratio of root to branch vegetative development, leaf area index, and leaf shape. [380] Phenotype can be assessed by any suitable means. The plants can be evaluated based on their general morphology. Transgenic plants can be observed with the naked eye, can be weighed and their height measured. The plant can be examined by isolating individual layers of plant tissue, namely phloem and cambium, which is further sectioned into meristematic cells, early expansion, late expansion, secondary wall formation, and late cell maturation. See, e.g., Hertzberg, supra. The plants also can be assessed using microscopic analysis or chemical analysis.

[381] Microscopic analysis includes examining cell types, stage of development, and stain uptake by tissues and cells. Fiber morphology, such as fiber wall thickness and microfibril angle of wood pulp fibers can be observed using, for example, microscopic transmission ellipsometry. See Ye and Sundstrδm, Tappi J. 80:181 (1997). Wood strength, density, and grain slope in wet wood and standing trees can be determined by measuring the visible and near infrared spectral data in conjunction with multivariate analysis. See U.S. Patent Application Publication Nos. 2002/0107644 and 2002/0113212. Lumen size can be measured using scanning electron microscopy. Lignin structure and chemical properties can be observed using nuclear magnetic resonance spectroscopy as described in Marita et al., J. Chem. Soc, Perkin Trans. / 2939 (2001).

[382] The biochemical characteristic of lignin, cellulose, carbohydrates and other plant extracts can be evaluated by any standard analytical method known including spectrophotometry, fluorescence spectroscopy, HPLC, mass spectroscopy, and tissue staining methods.

[383] In one embodiment, the making of a transformed plant comprises transforming a plant cell with a DNA construct and culturing the transformed plant cell under conditions that promote growth of a plant. [384] As used herein, "transformation" refers to a process by which a nucleic acid is inserted into the genome of a plant cell. Such insertion encompasses stable introduction into the plant cell and transmission to progeny. Transformation also refers to transient insertion of a nucleic acid, wherein the resulting transformant transiently expresses the nucleic acid. Transformation can occur under natural or artificial conditions using various methods well known in the art. See, e.g., Glick and Thompson (Eds.), Methods In Plant Molecular Biology, CRC Press, Boca Raton, FIa. (1993). Transformation can be achieved by any known method for the insertion of nucleic acid sequences into a prokaryotic or eukaryotic host cell, including transformation protocols (see, e.g., Horsch et al., Science 227:1229-31 (1985), viral infection, whiskers, electroporation (see, e.g., Rhodes et al., Science 240(4849):204-207 (1988), microinjection, polyethylene glycol- treatment (see, e.g., Lyznik et al., Plant MoI. Biol. 73:151-161 (1989), heat shock, lipofection, and particle bombardment (see, e.g., Klein et al., Plant Physiol. 91440-444 (1989) and Boynton et al., Science 240(4858): 1534-1538 (1988)). Transformation can also be accomplished using chloroplast transformation as described in, for example, Svab et al., Proc. Natl Acad. Sci. 57:8526-30 (1990).

[385] Plant transformation strategies are described in, for example, U.S. Patent Nos. 5,159,135 (cotton), 5,981 ,840 (corn), 5,914,451 (soybean), and WO 00/12715 (eucalyptus), which are incorporated by reference in their entirety. Additional plant transformation strategies and techniques are reviewed in Birch, R. G., Ann. Rev. Plant Physiol. Plant MoI. Biol. 48:297

(1997) and Forester et al., Exp. Agric. 33:15-33 (1997), and are incorporated by reference in their entirety

[386] Methods for transforming tree species are well known in the art. In accordance with one embodiment of the invention, genotype-independent transformation of Eucalyptus explants and generation of transgenic progeny can be accomplished by transformation using Agrobacterium. A tree explant can be, although need not be, harvested and cultured on a pre-culture medium before transformation. Although a pre-culture medium is not necessary, use of such a medium can increase transformation efficiency and plant regeneration. A pre-culture medium is a nutrient medium upon which plant explants can be cultured before transformation with Agrobacterium. Any pre-culture media and time periods of culture can be used. The pre-culture medium contains an Agrobacterium inducer, such as acetosyringone. The pre-culture medium can optionally contain plant growth regulators, including auxin and cytokinin. Pre-culture medium can be prepared using and appropriate salt medium, including, but not limited to Woody Plant Medium (WPM) salts (Lloyd and McCown, Combined Proceedings of the International Plant Propagators Society 30:421-427,1980), Murashige and Skoog medium (Sigma Aldrich, St. Louis, MO) or Lepoivre medium. The pre-culture medium can contain Agrobacterium inducers, such as, for example acetosyringone. Optionally, pre-culture medium can contain auxin, cytokinin, or both auxin and cytokinin. An exemplary plant pre-culture medium is shown in TABLE 5. TABLE 5: Exemplary Plant Pre-Culture Medium.

[387] In this transformation method, plant explants can be pre-cultured for four days in the dark on the pre-culture medium. Induced Agrobacterium culture can be prepared by methods known in the art. The induced culture is applied to a plant explant. Explants can be transformed by application of Agrobacterium culture to the explant, vacuum infiltration, floral dip, etc. Following transformation, Agrobacterium culture-treated explants can be co- cultivated with Agrobacterium under light or dark conditions for 2-10 days. In one embodiment, the explants are co-cultivated with Agrobacterium under light or dark conditions for 4 days.

[388] Following co-cultivation, explants can be transferred to regeneration medium with 400 mg/L timentin. Explants can be cultured on regeneration medium before transfer to a selection medium. In one embodiment, explants are cultured on regeneration medium for four days. Any suitable selection medium can be used. In one embodiment, the selection medium is the regeneration medium supplemented with both timentin and an herbicide selection agent. TABLE 6 provides an exemplary regeneration medium.

TABLE 6: Exemplary Plant Regeneration Medium.

[389] Shoot clumps that survive selection are maintained on regeneration medium containing herbicide and timentin. The shoot clumps can be transferred until shoots proliferate and initially elongate. In one embodiment, the shoot clumps are transferred every 3 weeks.

[390] Any reporter gene can be used, such as, for example, GFP, luciferase, or GUS. See, e.g., B. Miki and S. McHugh, J. Biotechnol. 107(3)^93-232 (2004).

[391] In one embodiment, GUS staining can performed to monitor the frequency of Agrobacterium infection and to ensure that the selected shoots are not escapes or chimeras. Leaf and stem tissues from the regenerated shoots can be stained for reporter gene expression immediately upon shoot development. For example, to determine GUS activity, the explants can be incubated in a substrate comprising 100 mM phosphate buffer (pH 7.0), 0.05% dimethyl suphoxide, 0.05% Triton X-100, 10 mM EDTA, 0.5 mM potassium ferrocyanide, and 1.5 mg/ml 5-bromo-4-chloro-3-indolyl-β-D- glucuronide (X-gluc). The explants can then be subjected to 10 minutes of vacuum before an overnight incubation at 37 0 C prior to counting GUS foci. [0392] In accordance with another embodiment, transformation of Pinus is accomplished using the methods described in U.S. Patent Application Publication No. 2002/0100083.

C. Compositions and Methods for Enhancing Woody Plants

[393] Another aspect of the invention provides methods of obtaining wood and/or making wood pulp from a plant transformed with a DNA construct of the invention. Methods of producing a transgenic plant are provided above and are known in the art. A transformed plant can be cultured or grown under any suitable conditions. For example, pine can be cultured and grown as described in U.S. Patent Application Publication No. 2002/0100083. Eucalyptus can be cultured and grown as in, for example, Rydelius, et al., "Growing Eucalyptus for Pulp and Energy," presented at the Mechanization in Short Rotation, Intensive Culture Forestry Conference, Mobile, AL, 1994. Wood and wood pulp can be obtained from the plant by any means known in the art.

[394] As noted above, the wood or wood pulp obtained in accordance with this invention may demonstrate improved characteristics including, but not limited to any one or more of lignin composition, lignin structure, wood

composition, cellulose polymerization, fiber dimensions, ratio of fibers to other plant components, plant cell division, plant cell development, number of cells per unit area, cell size, cell shape, cell wall composition, rate of wood formation, aesthetic appearance of wood, formation of stem defects, rate of growth, rate of root formation ratio of root to branch vegetative development, leaf area index, and leaf shape include increased or decreased lignin content, increased accessibility of lignin to chemical treatments, improved reactivity of lignin, increased or decreased cellulose content increased dimensional stability, increased tensile strength, increased shear strength, increased compression strength, increased shock resistance, increased stiffness, increased or decreased hardness, decreased spirality, decreased shrinkage, and differences in weight, density, and specific gravity.

II. Expression Profiling of Cell Signaling Genes

[395] The present invention also provides methods and tools for performing expression profiling of cell signaling genes. Expression profiling is useful in determining whether genes are transcribed or translated, comparing transcript levels for particular genes in different tissues, genotyping, estimating DNA copy number, determining identity of descent, measuring mRNA decay rates, identifying protein binding sites, determining subcellular localization of gene products, correlating gene expression to a phenotype or other phenomenon, and determining the effect on other genes of the manipulation of a particular gene. Expression profiling is particularly useful for identifying gene expression in complex, multigenic events. For this reason, expression profiling is useful in correlating polysaccharide synthesis gene expression to plant phenotype and formation of plant tissues and the interconnection thereof to the polysaccharide biosynthesis.

[396] Only a small fraction of a plant's cell signaling genes are expressed at a given time in a given tissue sample, and all of the expressed genes may not affect the plant phenotype. To identify genes capable of affecting a phenotype of interest, the present invention provides methods and tools for determining, for example, a cell signaling gene expression profile at a given

point in plant development and a cell signaling gene expression profile a given tissue sample. The invention also provides methods and tools for identifying cell signaling genes whose expression can be manipulated to alter plant phenotype. In support of these methods, the invention also provides methods and tools that distinguish expression of different genes of the same family, such as, for example, MAP Kinase and MAP kinase kinase proteins. [397] As used herein, "gene expression" refers to the process of transcription of a DNA sequence into an RNA sequence, followed by translation of the RNA into a protein, which may or may not undergo post-translational processing. Thus, the relationship between plant phenotype and cell signaling gene expression can be observed by detecting, quantitatively or qualitatively, changes in the level of RNA or protein. As used herein, the term "biological activity" includes, but is not limited to, the activity of a protein gene product, including enzyme activity, such as, for example, kinase activity. [398] The present invention provides oligonucleotides that are useful in these expression profiling methods. Each oligonucleotide is capable of hybridizing under a given set of conditions to a cell signaling gene or gene product. In one aspect of the invention, a plurality of oligonucleotides is provided, wherein each oligonucleotide hybridizes under a given set of conditions to a different cell signaling gene product. Examples of oligonucleotides of the present invention include SEQ ID NOs: 395-583. Each of the oligos of SEQ ID NOs 395-583 hybridizes under standard conditions to a different gene product of one of SEQ ID NOs: 1-197. The oligonucleotides of the invention are useful in determining the expression of one or more cell signaling genes in any of the above-described methods.

A. Cell, Tissue, Nucleic Acid, and Protein Samples

[399] Samples for use in methods of the present invention may be derived from plant tissue. Suitable plant tissues include, but are not limited to, somatic embryos, pollen, leaves, stems, calli, stolons, microtubers, shoots, xylem, male strolbili, pollen cones, vascular tissue, apical meristem, vascular cambium, xylem, root, flower, and seed.

[400] According to the present invention "plant tissue" is used as described previously herein. Plant tissue can be obtained from any of the plants types or species described' supra.

[401] In accordance with one aspect of the invention, samples can be obtained from plant tissue at different developmental stages, from plant tissue at various times of the year (e.g. spring versus summer), from plant tissues subject to different environmental conditions (e.g. variations in light and temperature) and/or from different types of plant tissue and cells. In accordance with one embodiment, plant tissue is obtained during various stages of maturity and during different seasons of the year. In a further embodiment, plant tissue is obtained from plants displaying different phenotypes. For example, plant tissue can be collected from stem dividing cells, differentiating xylem, early developing wood cells, differentiated early wood cells, and differentiated late wood cells. As another example, gene expression in a sample obtained from a plant with developing wood can be compared to gene expression in a sample obtained from a plant which does not have developing wood. As a further example, gene expression in a sample obtained from a plant displaying a reaction wood phenotype, such as compression wood or tension wood, can be compared to gene expression in a sample obtained from a plant which does not have reaction wood. [402] Differentiating xylem includes samples obtained from reaction wood. Reaction wood includes compression wood, side-wood, tension wood, and normal vertical xylem. Methods of obtaining samples for expression profiling from pine and eucalyptus are known. See, e.g., Allona et al., Proc. Nat'l Acad. Sci. 95:9693-8 (1998) and Whetton et al., Plant MoI. Biol. 47:275-91 , and Kirst et al., Int'l Union of Forestry Research Organizations Biennial Conference, S6.8 (June 2003, Umea, Sweden).

[403] In one embodiment of the invention, gene expression in one type of tissue is compared to gene expression in a different type of tissue or to gene expression in the same type of tissue in a difference stage of development. Gene expression can also be compared in one type of tissue which is

sampled at various times during the year (different seasons). For example, gene expression in juvenile secondary xylem can be compared to gene expression in mature secondary xylem. Similarly, gene expression in cambium can be compared to gene expression in xylem. Furthermore, gene expression in apical meristems can be compared to gene expression in cambium.

[404] In another embodiment of the invention, a sample is obtained from a plant having a specific phenotype and gene expression in that sample is compared to a sample obtained from a plant of the same species that does not have that phenotype. For example, a sample can be obtained from a plant exhibiting a fast rate of growth and gene expression can be compared with that of a sample obtained from a plant exhibiting a normal or slow rate of growth. Differentially expressed genes identified from such a comparison can be correlated with growth rate and, therefore, useful for manipulating growth rate.

[405] In a further embodiment, a sample is obtained from clonally propagated plants. In one embodiment the clonally propagated plants are of the species Pinus or Eucalyptus. Individual ramets from the same genotype can be sacrificed at different times of year. Thus, for any genotype there can be at least two genetically identical trees sacrificed, early in the season and late in the season. Each of these trees can be divided into juvenile (top) to mature (bottom) samples. Further, tissue samples can be divided into, for example, phloem to xylem, in at least 5 layers of peeling. Each of these samples can be evaluated for phenotype and gene expression.

[406] Where cellular components may interfere with an analytical technique, such as a hybridization assay, enzyme assay, a ligand binding assay, or a biological activity assay, it may be desirable to isolate the gene products from such cellular components. Gene products, including nucleic acid and amino acid gene products, can be isolated from cell fragments or lysates by any method known in the art.

[407] Nucleic acids used in accordance with the invention can be prepared by any available method or process, or by other processes as they become known in the art. Conventional techniques for isolating nucleic acids are detailed, for example, in Tijssen, Laboratory Techniques in Biochemistry and Molecular Biology, Hybridization With Nucleic Acid Probes, chapter 3 (Elsevier Press, 1993), Berger and Kimmel, Methods Enzymol. 152:1 (1987), and Gibco BRL & Life Technologies Trizol RNA Isolation Protocol, Form No. 3786 (2000). Techniques for preparing nucleic acid samples, and sequencing polynucleotides from pine and eucalyptus are known. See, e.g., Allona et a/., supra and Whetton et a/., supra.

[408] A suitable nucleic acid sample can contain any type of nucleic acid derived from the transcript of a cell signaling gene, i.e., RNA or a subsequence thereof or a nucleic acid for which an mRNA transcribed from a cell signaling gene served as a template. Suitable nucleic acids include cDNA reverse-transcribed from a transcript, RNA transcribed from that cDNA, DNA amplified from the cDNA, and RNA transcribed from the amplified DNA. Detection of such products or derived products is indicative of the presence and/or abundance of the transcript in the sample. Thus, suitable samples include, but are not limited to, transcripts of the gene or genes, cDNA reverse- transcribed from the transcript, cRNA transcribed from the cDNA, DNA amplified from the genes, and RNA transcribed from amplified DNA. As used herein, the category of "transcripts" includes but is not limited to pre-mRNA nascent transcripts, transcript processing intermediates, and mature mRNAs and degradation products thereof.

[409] It is not necessary to monitor all types of transcripts to practice the invention. For example, the expression profiling methods of the invention can be conducted by detecting only one type of transcript, such as mature mRNA levels only.

[410] In one aspect of the invention, a chromosomal DNA or cDNA library (comprising, for example, fluorescently labeled cDNA synthesized from total

cell mRNA) is prepared for use in hybridization methods according to recognized methods in the art. See Sambrook et al., supra. [411] In another aspect of the invention, mRNA is amplified using, e.g., the MessageAmp kit (Ambion). In a further aspect, the mRNA is labeled with a detectable label. For example, mRNA can be labeled with a fluorescent chromophore, such as CyDye (Amersham Biosciences). [412] In some applications, it may be desirable to inhibit or destroy RNase that often is present in homogenates or lysates, before use in hybridization techniques. Methods of inhibiting or destroying nucleases are well known. In one embodiment of the invention, cells or tissues are homogenized in the presence of chaotropic agents to inhibit nuclease. In another embodiment, RNase is inhibited or destroyed by heat treatment, followed by proteinase treatment.

[413] Protein samples can be obtained by any means known in the art. Protein samples useful in the methods of the invention include crude cell lysates and crude tissue homogenates. Alternatively, protein samples can be purified. Various methods of protein purification well known in the art can be found in Marshak et al., Strategies for Protein Purification and Characterization: A Laboratory Course Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY (1996). B. Detecting Levels of Gene Expression

[414] For methods of the invention that comprise detecting a level of gene expression, any method for observing gene expression can be used, without limitation. Such methods include traditional nucleic acid hybridization techniques, polymerase chain reaction (PCR) based methods, and protein determination. The invention includes detection methods that use solid support-based assay formats as well as those that use solution-based assay formats.

[415] Absolute measurements of the expression levels need not be made, although they can be made. The invention includes methods comprising comparisons of differences in expression levels between samples.

Comparison of expression levels can be done visually or manually, or can be automated and done by a machine, using for example optical detection means. Subrahmanyam et a/., Blood. 97: 2457 (2001); Prashar et a/., Methods Enzymol. 303: 258 (1999). Hardware and software for analyzing differential expression of genes are available, and can be used in practicing the present invention. See, e.g., GehStat Software and GeneExpress ® GX Explorer™ Training Manual, supra; Baxevanis & Francis-Ouellette, supra. [416] In accordance with one embodiment of the invention, nucleic acid hybridization techniques are used to observe gene expression. Exemplary hybridization techniques include Northern blotting, Southern blotting, solution hybridization, and S1 nuclease protection assays.

[417] Nucleic acid hybridization typically involves contacting an oligonucleotide probe and a sample comprising nucleic acids under conditions where the probe can form stable hybrid duplexes with its complementary nucleic acid through complementary base pairing. For example, see PCT application WO 99/32660; Berger & Kimmel, Methods Enzymol. 152: 1 (1987). The nucleic acids that do not form hybrid duplexes are then washed away leaving the hybridized nucleic acids to be detected, typically through detection of an attached detectable label. The detectable label can be present on the probe, or on the nucleic acid sample. In one embodiment, the nucleic acids of the sample are detectably labeled polynucleotides representing the mRNA transcripts present in a plant tissue (e.g., a cDNA library). Detectable labels are commonly radioactive or fluorescent labels, but any label capable of detection can be used. Labels can be incorporated by several approached described, for instance, in WO 99/32660, supra. In one aspect RNA can be amplified using the MessageAmp kit (Ambion) with the addition of aminoallyl-UTP as well as free UTP. The aminoallyl groups incorporated into the amplified RNA can be reacted with a fluorescent chromophore, such as CyDye (Amersham Biosciences) [418] Duplexes of nucleic acids are destabilized by increasing the temperature or decreasing the salt concentration of the buffer containing the

nucleic acids. Under low stringency conditions (e.g., low temperature and/or high salt) hybrid duplexes (e.g., DNA:DNA, RNA:RNA or RNA:DNA) will form even where the annealed sequences are not perfectly complementary. Thus, specificity of hybridization is reduced at lower stringency. Conversely, at higher stringency (e.g., higher temperature and/or lower salt and/or in the presence of destabilizing reagents) hybridization tolerates fewer mismatches. [419] Typically, stringent conditions for short probes (e.g., 10 to 50 nucleotide bases) will be those in which the salt concentration is at least about 0.01 to 1.0 M at pH 7.0 to 8.3 and the temperature is at least about 30 0 C. Stringent conditions can also be achieved with the addition of destabilizing agents such as formamide.

[420] Under some circumstances, it can be desirable to perform hybridization at conditions of low stringency, e.g., 6 x SSPE-T (0.9 M NaCI, 60 mM NaH 2 PO 4 , pH 7.6, 6 mM EDTA, 0.005% Triton) at . 37 0 C, to ensure hybridization. Subsequent washes can then be performed at higher stringency (e.g., 1 * SSPE-T at 37°C) to eliminate mismatched hybrid duplexes. Successive washes can be performed at increasingly higher stringency (e.g., down to as low as 0.25* SSPE-T at 37 0 C to 5O 0 C) until a desired level of hybridization specificity is obtained.

[421] In general, standard conditions for hybridization is a compromise between stringency (hybridization specificity) and signal intensity. Thus, in one embodiment of the invention, the hybridized nucleic acids are washed at successively higher stringency conditions and read between each wash. Analysis of the data sets produced in this manner will reveal a wash stringency above which the hybridization pattern is not appreciably altered and which provides adequate signal for the particular oligonucleotide probes of interest. For example, the final wash may be selected as that of the highest stringency that produces consistent results and that provides a signal intensity greater than approximately 10% of the background intensity. 1. Oligonucleotide Probes

[422] Oligonucleotide probes useful in nucleic acid hybridization techniques employed in the present invention are capable of binding to a nucleic acid of complementary sequence through one or more types of chemical bonds, usually through complementary base pairing via hydrogen bond formation. A probe can include natural bases (Ae., A, G, U, C or T) or modified bases (7- deazaguanosine, inosine, etc.). In addition, the nucleotide bases in the probes can be joined by a linkage other than a phosphodiester bond, so long as it does not interfere with hybridization. Thus, probes can be peptide nucleic acids in which the constituent bases are joined by peptide bonds rather than phosphodiester linkages.

[423] Oligonucleotide probes can be prepared by any means known in the art. Probes useful in the present invention are capable of hybridizing to a nucleotide product of a cell signaling gene, such as one of SEQ ID NOs: 1- 197. Probes useful in the invention can be generated using the nucleotide sequences disclosed in SEQ ID NOs: 1-197. The invention includes oligonucleotide probes having at least a 2, 10,15, 20, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, or 100 nucleotide fragment of a corresponding contiguous sequence of any one of SEQ ID NOs: 1-197. The invention includes oligonucleotides of less than 2, 1 , 0.5, 0.1 , or 0.05 kb in length. In one embodiment, the oligonucleotide is 60 nucleotides in length. In another embodiment, the oligonucleotide is 30 nucleotides in length. [424] Oligonucleotide probes can be designed by any means known in the art. See, e.g., Li and Stormo, Bioinformatics 17: 1067-76 (2001). Oligonucleotide probe design can be effected using software. Exemplary software includes ArrayDesigner, GeneScan, and ProbeSelect. Probes complementary to a defined nucleic acid sequence can be synthesized chemically, generated from longer nucleotides using restriction enzymes, or can be obtained using techniques such as polymerase chain reaction (PCR). PCR methods are well known and are described, for example, in lnnis et a/, eds., PCR Protocols: A Guide to Methods and Applications, Academic Press Inc. San Diego, Calif. (1990). The probes can be labeled, for example, with a

radioactive, biotinylated, or fluorescent tag. Optimally, the nucleic acids in the sample are labeled and the probes are not labeled. Oligonucleotide probes generated by the above methods can be used in solution or solid support- based methods.

[425] The invention includes oligonucleotide probes that hybridize to a product of the coding region or a 3' untranslated region (3' UTR) of a cell signaling gene. In one embodiment, the oligonucleotide probe hybridizes to the 3'UTR of any one of SEQ ID NOs: 1-197. The 3' UTR is generally a unique region of the gene, even among members of the same family. Therefore, the probes capable of hybridizing to a product of the 3' UTR can be useful for differentiating the expression of individual genes within a family where the coding region of the genes likely are highly homologous. This allows for the design of oligonucleotide probes to be used as members of a plurality of oligonucleotides, each capable of uniquely binding to a single gene. In another embodiment, the oligonucleotide probe comprises any one of SEQ ID NOs: 395-583. In another embodiment, the oligonucleotide probe consists of any one of SEQ ID NOs: 1-197.

2. Oligonucleotide Array Methods

[426] One embodiment of the invention employs two or more oligonucleotide probes in combination to detect a level of expression of one or more cell signaling genes, such as the genes of SEQ ID NOs: 1-197. In one aspect of this embodiment, the level of expression of two or more different genes is detected. The two or more genes may be from the same or different cell signaling gene families. Each of the two or more oligonucleotides may hybridize to a different one of the genes.

[427] One embodiment of the invention employs two or more oligonucleotide probes, each of which specifically hybridize to a polynucleotide derived from the transcript of a gene provided by SEQ ID NOs: 1-197. Another embodiment employs two or more oligonucleotide probes, at least one of which comprises a nucleic acid sequence of SEQ ID NOs: 395-583. Another

embodiment employs two or more oligonucleotide probes, at least one of which consists of SEQ ID NOs: 395-583.

[428] The oligonucleotide probes may comprise from about 5 to about 60, or from about 5 to about 500, nucleotide bases, such as from about 60 to about 100 nucleotide bases, including from about 15 to about 60 nucleotide bases. [429] One embodiment of the invention uses solid support-based oligonucleotide hybridization methods to detect gene expression. Solid support-based methods suitable for practicing the present invention are widely known and are described, for example, in PCT application WO 95/11755; Huber et al., Anal. Biochem. 299: 24 (2001); Meiyanto et al., Biotechniques. 31 : 406 (2001); Relogio et al., Nucleic Acids Res. 30:e51 (2002). Any solid surface to which oligonucleotides can be bound, covalently or non-covalently, can be used. Such solid supports include filters, polyvinyl chloride dishes, silicon or glass based chips, etc.

[430] One embodiment uses oligonucleotide arrays, i.e. microarrays, which can be used to simultaneously observe the expression of a number of genes or gene products. Oligonucleotide arrays comprise two or more oligonucleotide probes provided on a solid support, wherein each probe occupies a unique location on the support. The location of each probe may be predetermined, such that detection of a detectable signal at a given location is indicative of hybridization to an oligonucleotide probe of a known identity. Each predetermined location can contain more than one molecule of a probe, but each molecule within the predetermined location has an identical sequence. Such predetermined locations are termed features. There can be, for example, from 2, 10, 100, 1 ,000, 2,000 or 5,000 or more of such features on a single solid support. In one embodiment, each oligonucleotide is located at a unique position on an array at least 2, at least 3, at least 4, at least 5, at least 6, or at least 10 times.

[431] Oligonucleotide probe arrays for detecting gene expression can be made and used according to conventional techniques described, for example, in Lockhart et al., Nat'l Biotech. 14: 1675 (1996), McGaII et al., Proc. Nat'l

Acad. ScL USA 93: 13555 (1996), and Hughes et a/., Nature Biotechnol. 19:342 (2001). A variety of oligonucleotide array designs is suitable for the practice of this invention.

[432] In one embodiment the one or more oligonucleotides include a plurality of oligonucleotides that each hybridize to a different gene expressed in a particular tissue type. For example, the tissue can be developing wood. [433] In one embodiment, a nucleic acid sample obtained from a plant can be amplified and, optionally labeled with a detectable label. Any method of nucleic acid amplification and any detectable label suitable for such purpose can be used. For example, amplification reactions can be performed using, e.g. Ambion's MessageAmp, which creates "antisense" RNA or "aRNA" (complementary in nucleic acid sequence to the RNA extracted from the sample tissue). The RNA can optionally be labeled using CyDye fluorescent labels. During the amplification step, aaUTP is incorporated into the resulting aRNA. The CyDye fluorescent labels are coupled to the aaUTPs in a non- enzymatic reaction. Subsequent to the amplification and labeling steps, labeled amplified antisense RNAs are precipitated and washed with appropriate buffer, and then assayed for purity. For example, purity can be assay using a NanoDrop spectrophotometer. The nucleic acid sample is then contacted with an oligonucleotide array having, attached to a solid substrate (a "microarray slide"), oligonucleotide sample probes capable of hybridizing to nucleic acids of interest which may be present in the sample. The step of contacting is performed under conditions where hybridization can occur between the nucleic acids of interest and the oligonucleotide probes present on the array. The array is then washed to remove non-specifically bound nucleic acids and the signals from the labeled molecules that remain hybridized to oligonucleotide probes on the solid substrate are detected. The step of detection can be accomplished using any method appropriate to the type of label used. For example, the step of detecting can accomplished using a laser scanner and detector. For example, on can use and Axon

scanner which optionally uses GenePix Pro software to analyze the position of the signal on the microarray slide.

[434] Data from one or more microarray slides can be analyzed by any appropriate method known in the art.

[435] Oligonucleotide probes used in the methods of the present invention, including microarray techniques, can be generated using PCR. PCR primers used in generating the probes are chosen, for example, based on the sequences of SEQ ID NOs: 1-197, to result in amplification of unique fragments of cell signaling genes (i.e., fragments that hybridize to only one polynucleotide of any one of SEQ ID NOs: 1-197 under standard hybridization conditions). Computer programs are useful in the design of primers with the required specificity and optimal hybridization properties. For example, Li and Stormo, supra, discuss a method of probe selection using ProbeSelect which selects an optimum oligonucleotide probe based on the entire gene sequence as well as other gene sequences to be probed at the same time. [436] In one embodiment, oligonucleotide control probes also are used. Exemplary control probes can fall into at least one of three categories referred to herein as (1) normalization controls, (2) expression level controls and (3) negative controls. In microarray methods, one or more of these control probes may be provided on the array with the inventive cell signaling gene- related oligonucleotides.

[437] Normalization controls correct for dye biases, tissue biases, dust, slide irregularities, malformed slide spots, etc. Normalization controls are oligonucleotide or other nucleic acid probes that are complementary to labeled reference oligonucleotides or other nucleic acid sequences that are added to the nucleic acid sample to be screened. The signals obtained from the normalization controls, after hybridization, provide a control for variations in hybridization conditions, label intensity, reading efficiency and other factors that can cause the signal of a perfect hybridization to vary between arrays. In one embodiment, signals (e.g., fluorescence intensity or radioactivity) read

from all other probes used in the method are divided by the signal from the control probes, thereby normalizing the measurements.

[438] Virtually any probe can serve as a normalization control. Hybridization efficiency varies, however, with base composition and probe length.

Preferred normalization probes are selected to reflect the average length of the other probes being used, but they also can be selected to cover a range of lengths. Further, the normalization control(s) can be selected to reflect the average base composition of the other probes being used. In one embodiment, only one or a few normalization probes are used, and they are selected such that they hybridize well (i.e., without forming secondary structures) and do not match any test probes. In one embodiment, the normalization controls are mammalian genes.

[439] Expression level control probes hybridize specifically with constitutively expressed genes present in the biological sample. Virtually any constitutively expressed gene provides a suitable target for expression level control probes.

Typically, expression level control probes have sequences complementary to subsequences of constitutively expressed "housekeeping genes" including, but not limited to certain photosynthesis genes.

[440] As used herein, "negative control" probes are not complementary to any of the test oligonucleotides (i.e., the inventive cell signaling gene-related oligonucleotides), normalization controls, or expression controls. In one embodiment, the negative control is a mammalian gene which is not complementary to any other sequence in the sample.

[441] The terms "background" and "background signal intensity" refer to hybridization signals resulting from non-specific binding or other interactions between the labeled target nucleic acids (i.e., mRNA present in the biological sample) and components of the oligonucleotide array. Background signals also can be produced by intrinsic fluorescence of the array components themselves.

[442] A single background signal can be calculated for the entire array, or a different background signal can be calculated for each target nucleic acid. In

a one embodiment, background is calculated as the average hybridization signal intensity for the lowest 5 to 10 percent of the oligonucleotide probes being used, or, where a different background signal is calculated for each target gene, for the lowest 5 to 10 percent of the probes for each gene. Where the oligonucleotide probes corresponding to a particular cell signaling gene hybridize well and, hence, appear to bind specifically to a target sequence, they should not be used in a background signal calculation. Alternatively, background can be calculated as the average hybridization signal intensity produced by hybridization to probes that are not complementary to any sequence found in the sample (e.g., probes directed to nucleic acids of the opposite sense or to genes not found in the sample). In microarray methods, background can be calculated as the average signal intensity produced by regions of the array that lack any oligonucleotides probes at all.

3. PCR-Based Methods

[443] In another embodiment, PCR-based methods are used to detect gene expression. These methods include reverse-transcriptase-mediated polymerase chain reaction (RT-PCR) including real-time and endpoint quantitative reverse-transcriptase-mediated polymerase chain reaction (Q- RTPCR). These methods are well known in the art. For example, methods of quantitative PCR can be carried out using kits and methods that are commercially available from, for example, Applied BioSystems and Stratagene®. See also Kochanowski, Quantitative PCR Protocols (Humana Press, 1999); lnnis et al., supra.; Vandesompele et al., Genome Biol. 3: RESEARCH0034 (2002); Stein, CeII MoI. Life Sci. 59: 1235 (2002). [444] Gene expression can also be observed in solution using Q-RTPCR. Q- RTPCR relies on detection of a fluorescent signal produced proportionally during amplification of a PCR product. See lnnis et al., supra. Like the traditional PCR method, this technique employs PCR oligonucleotide primers, typically 15-30 bases long, that hybridize to opposite strands and regions flanking the DNA region of interest. Additionally, a probe (e.g., TaqMan®,

Applied Biosystems) is designed to hybridize to the target sequence between the forward and reverse primers traditionally used in the PCR technique. The probe is labeled at the 5 1 end with a reporter fluorophore, such as 6- carboxyfluorescein (6-FAM) and a quencher fluorophore like 6-carboxy- tetramethyl-rhodamine (TAMRA). As long as the probe is intact, fluorescent energy transfer occurs which results in the absorbance of the fluorescence emission of the reporter fluorophore by the quenching fluorophore. As Taq polymerase extends the primer, however, the intrinsic 5 1 to 3' nuclease activity of Taq degrades the probe, releasing the reporter fluorophore. The increase in the fluorescence signal detected during the amplification cycle is proportional to the amount of product generated in each cycle. [445] The forward and reverse amplification primers and internal hybridization probe is designed to hybridize specifically and uniquely with one nucleotide derived from the transcript of a target gene. In one embodiment, the selection criteria for primer and probe sequences incorporates constraints regarding nucleotide content and size to accommodate TaqMan ® requirements.

[446] SYBR Green ® can be used as a probe-less Q-RTPCR alternative to the Taqman ® -type assay, discussed above. ABI Prism ® 7900 Sequence Detection System User Guide Applied Biosystems, chap. 1-8, App. A-F. (2002).

[447] A device measures changes in fluorescence emission intensity during PCR amplification. The measurement is done in "real time," that is, as the amplification product accumulates in the reaction. Other methods can be used to measure changes in fluorescence resulting from probe digestion. For example, fluorescence polarization can distinguish between large and small molecules based on molecular tumbling (see, e.g., U.S. Patent No. 5,593,867).

4. Protein Detection Methods

[448] Proteins can be observed by any means known in the art, including immunological methods, enzyme assays and protein array/proteomics techniques.

[449] Measurement of the translational state can be performed according to several protein methods. For example, whole genome monitoring of protein -- the "proteome" ~ can be carried out by constructing a microarray in which binding sites comprise immobilized, preferably monoclonal, antibodies specific to a plurality of proteins having an amino acid sequence of any of SEQ ID NOs: 198-394 or proteins encoded by the genes of SEQ ID NOs: 1-197 or conservative variants thereof. See Wildt et al., Nature Biotechnol. 18: 989 (2000). Methods for making polyclonal and monoclonal antibodies are well known, as described, for instance, in Harlow & Lane, Antibodies: A Laboratory Manual (Cold Spring Harbor Laboratory Press, 1988). [450] Alternatively, proteins can be separated by two-dimensional gel electrophoresis systems. Two-dimensional gel electrophoresis is well-known in the art and typically involves isoelectric focusing along a first dimension followed by SDS-PAGE electrophoresis along a second dimension. See, e.g., Hames et al, , Gel Electrophoresis of Proteins: A Practical Approach (IRL Press, 1990). The resulting electropherograms can be analyzed by numerous techniques, including mass spectrometric techniques, western blotting and immunoblot analysis using polyclonal and monoclonal antibodies, and internal and N-terminal micro-sequencing.

[451] In another embodiment, cell signaling proteins can be detected by directly measuring their enzymatic activity. For example, cytokinin oxidase activity can be measured by a simple colormetric assay. See Libreros-Minotta et al., Anal. Biochem. 237:339-341 (1995). Likewise, cell signaling gene products can be detected directly or indirectly by the functional assays described supra in Part IA of this description.

C. Correlating Gene Expression to Phenotype

[452] As discussed above, the invention provides methods and tools to correlate gene expression to plant phenotype. Gene expression may be

examined in a plant having a phenotype of interest and compared to a plant that does not have the phenotype or has a different phenotype. Such a phenotype includes, but is not limited to, increased drought tolerance, herbicide resistance, reduced or increased height, reduced or increased branching, enhanced cold and frost tolerance, improved vigor, enhanced color, enhanced health and nutritional characteristics, improved storage, enhanced yield, enhanced salt tolerance, enhanced resistance of the wood to decay, enhanced resistance to fungal diseases, altered attractiveness to insect pests enhanced heavy metal tolerance, increased disease tolerance, increased insect tolerance, increased water-stress tolerance, enhanced sweetness, improved texture, decreased phosphate content, increased germination, increased micronutrient uptake, improved starch composition, improved flower longevity, production of novel resins, increased or decreased cellulose content, increased or decreased lignin content, increased or decreased nonlignin cell wall phenolics and production of novel proteins or peptides.

[453] In another embodiment, the phenotype includes one or more of the following traits: propensity to form reaction wood, a reduced period of juvenility, an increased period of juvenility, self-abscising branches, accelerated reproductive development or delayed reproductive development, and accelerated regeneration.

[454] In a further embodiment, the phenotype that is different from the comparative plant includes one or more of the following: lignin quality, lignin structure, wood composition, wood appearance, wood density, wood strength, wood stiffness, cellulose polymerization, fiber dimensions, lumen size, proportion of rays, proportion of vessel elements, other plant components, plant cell division, plant cell development, number of cells per unit area, cell size, cell shape, cell wall composition, proportion of nonlignin cell wall phenolics, rate of wood formation, aesthetic appearance of wood, formation of stem defects, average microfibril angle, width of the S2 cell wall layer, rate of growth, rate of root formation ratio of root to branch vegetative development,

leaf area index, and leaf shape. Phenotype can be assessed by any suitable means as discussed above, such as, for example Hertzberg, supra, Ye and Sundstrόm, supra, U.S. Patent Application Publication Nos. 2002/0107644 and 2002/0113212, Marita et al., supra.

[0455] It will be apparent to those skilled in the art that various modifications and variations can be made in the methods and compositions of the present invention without departing from the spirit or scope of the invention. Thus, it is intended that the present invention cover the modifications and variations of this invention provided they come within the scope of the appended claims and their equivalents.

[0456] The following examples are given to illustrate the present invention. It should be understood, however, that the invention is not to be limited to the specific conditions or details described in these examples. Throughout the specification, any and all references to a publicly available document, including a U.S. patent, are specifically incorporated by reference in their entirety.

EXAMPLES

Example 1.

[457] Example 1 demonstrates the isolation and characterization of cell signaling genes from E. grandis and P. radiata.

[458] Total RNA was extracted from plant tissue (using the protocol of Chang et a/., Plant MoI. Biol. Rep. 11 :113-116 (1993). Plant tissue samples were obtained from phloem (P), cambium (C), expanding xylem (X1), and differentiating and lignifying xylem (X2).

[459] mRNA was isolated from the total RNA preparation using either a PoIy(A) Quik mRNA Isolation Kit (Stratagene, La JoIIa, CA) or Dynal Beads Oligo (dT) 25 (Dynal, Skogen, Norway). cDNA expression libraries were constructed from the purified mRNA by reverse transcriptase synthesis followed by insertion of the resulting cDNA clones in Lambda ZAP using a ZAP Express cDNA Synthesis Kit (Stratagene), according to the using the

manufacturer's protocol. The resulting cDNAs were packaged using a Gigapack Il Packaging Extract (Stratagene) using an aliquot (1 - 5 μl_) from the 5 μl_ ligation reaction dependent upon the library. Mass excision of the library was done using XL1-Blue MRF' cells and XLOLR cells (Stratagene) with ExAssist helper phage (Stratagene). The excised phagemids were diluted with NZY broth (Gibco BRL, Gaithersburg, MD) and plated out onto LB-kanamycin agar plates containing X-gal and isopropylthio-beta-galactoside (IPTG).

[460] Of the colonies plated and selected for DNA miniprep, 99% contained an insert suitable for sequencing. Positive colonies were cultured in NZY broth with kanamycin and cDNA was purified by means of alkaline lysis and polyethylene glycol (PEG) precipitation. Agarose gel at 1% was used to screen sequencing templates for chromosomal contamination. Dye primer sequences were prepared using a Turbo Catalyst 800 machine (Perkin Elmer/Applied Biosystems Division, Foster City, CA) according to the manufacturer's protocol.

[461] DNA sequence for positive clones was obtained using a Perkin Elmer/Applied Biosystems Division Prism 377 sequencer. cDNA clones were sequenced first from the 5' end and, in some cases, also from the 3' end. For some clones, internal sequence was obtained using either Exonuclease III deletion analysis, yielding a library of differentially sized subclones in pBK- CMV, or by direct sequencing using gene-specific primers designed to identify regions of the gene of interest. The determined cDNA sequences are provided in SEQ ID NOS: 1-197. The predicted polypeptide sequences are SEQ ID NOs: 198-394.

[462] To identify cell signaling gene candidates in P. radiata and E. grandis databases, cDNA sequences were compared to the Arabidopsis cell signaling gene superfamilies. Richmond and Somerville, Plant Physiol. 124:495 (2000). [463] Next, public domain sequences (by SWISS-PROT/TrEMBL ID's) were used to search against the pine and eucalyptus databases (non-redundant by contig, expect <1.0e '2 ). Probably pine and eucalyptus gene candidates were

obtained. Of these, several pine and eucalyptus gene candidates were potentially full length {i.e. contained start Met) or near full length sequences. [464] The contig consensus DNA and protein sequences were then obtained for all gene candidates and duplicate sequences were identified. Multiple alignment was then carried out with the protein sequences. The protein alignment was created using the remaining pine and eucalyptus sequences along with the Arabidopsis members, and previously identified cell signaling genes. From the protein alignment, a dendogram was created. This dendogram grouped the sequence hits into cell signaling families. These sequences were analyzed by primer walking to provide a full length sequence (best HT pick from the contig analyzed for full length sequence). [465] The public domain cell signaling sequences from maize, cotton, rice, and poplar were also extracted and blasted against the pine and eucalyptus databases. The completed primer walked pine and eucalyptus sequences were also blasted against ownseq and the top 500 hits were taken. This was done so that the sequences could be used to search further and ensure that nothing in the pine and eucalyptus databases had been missed by using the Arabidopsis superfamily. This search resulted in the identification of additional sequences not found in the previous searches. These sequences were then also sent for primer walked full length sequence. [466] After removing a small number of additional duplicates after primer walking, the pine and eucalyptus primer walked cell signaling genes were identified. The classification of these sequences was confirmed by alignment with ClustalX, the corresponding dendogram, and MEME/MAST analysis.

Example 2.

[467] Example 2 demonstrates how additional regions either 5' or 3' of target sequences are identified and characterized.

[468] To identify additional sequence 5 1 or 3' of a partial cDNA sequence in a cDNA library, 5' and 3' rapid amplification of cDNA ends (RACE) was performed, using the SMART RACE cDNA amplification kit (Clontech Laboratories, Palo Alto, Calif.). Generally, the method entailed first isolating

poly(A) mRNA, performing first and second strand cDNA synthesis to generate double stranded cDNA, blunting cDNA ends, and then ligating of the SMART RACE. Adaptor to the cDNA to form a library of adaptor-ligated ds cDNA. Gene-specific primers were designed to be used along with adaptor specific primers for both 5 1 and 3' RACE reactions. Using 5' and 3' RACE reactions, 5' and 3' RACE fragments were obtained, sequenced, and cloned. The process may be repeated until 5 1 and 3 1 ends of the full-length gene were identified. A full-length cDNA may generated by PCR using primers specific to 5' and 3' ends of the gene by end-to-end PCR.

[469] For example, to amplify the missing 5' region of a gene from first-strand cDNA, a primer was designed 5'→3' from the opposite strand of the template sequence, and from the region between ~100-200 bp of the template, sequence. A successful amplification should give an overlap of ~100 bp of DNA sequence between the 5' end of the template and PCR product. [470] RNA was extracted from four pine tissues, namely seedling, xylem, phloem and structural root using the Concert Reagent Protocol (Invitrogen, Carlsbad, CA) and standard isolation and extraction procedures. The resulting RNA was then treated with DNase, using 10U/μl DNase I (Roche Diagnostics, Basel, Switzerland). For 100 μg of RNA, 9 μl 10x DNase buffer (invitrogen, Carlsbad, CA), 10 μl of Roche DNase I and 90 μl of Rnase-free water was used. The RNA was then incubated at room temperature for 15 minutes and 1/10 volume 25 mM EDTA is added. A RNeasy mini kit (Qiagen, Venlo, The Netherlands) was used for RNA purification according to manufacturer's protocol.

[471] To synthesize cDNA, the extracted RNA from xylem, phloem, seedling and root was used and the SMART RACE cDNA amplification kit (Clontech Laboratories Inc, Palo Alto, CA) was followed according to manufacturer's protocol. For the RACE PCR 1 the cDNA from the four tissue types was combined. The master mix for PCR was created by combining equal volumes of cDNA from xylem, phloem, root and seedling tissues. PCR reactions were performed in 96 well PCR plates, with 1 μl of primer from primer dilution plate

(1OmM) to corresponding well positions. 49 μl of master mix is aliquoted into the PCR plate with primers. Thermal cycling commenced on a GeneAmp 9700 (Applied Biosystems, Foster City, CA) obtaining 94 0 C for 5 seconds, 72 0 C for 3 minutes, 5 cycles, 94 0 C for 5 seconds, 7O 0 C for 10 seconds, and 72 0 C for 3 minutes, repeated for 5 cycles. Subsequently, the thermal cycling occurred at 94 0 C for 5 seconds, 68 0 C for 10 sec, and 72 0 C for 3 minutes, repeated for 25 cycles.

[472] cDNA was separated on an agarose gel following standard procedures. Gel fragments were excised and eluted from the gel by using the Qiagen 96- well Gel Elution kit, following the manufacturer's instructions. [473] PCR products were ligated into pGEMTeasy (Promega, Madison, Wl) in a 96 well plate overnight according to the following specifications: 60-80 ng of DNA, 5 μl 2X rapid ligation buffer, 0.5 μl pGEMT easy vector, 0.1 μl DNA ligase, filled to 10 μl with water, and incubated overnight. [474] Each clone was transformed into E. coli following standard procedures and DNA was extracted from 12 clones picked by following standard protocols. DNA extraction and the DNA quality was verified on an 1% agarose gel. The presence of the correct size insert in each of the clones was determined by restriction digests, using the restriction endonuclease EcoRI, and gel electrophoresis, following standard laboratory procedures. [475] The transformation of Eucalyptus elite clones with a sense UDP- glucose binding domain sequence operably-linked to a constitutive promoter confers an enhanced growth phenotype, as evidenced by increases in cellulose synthesis, primary cell wall synthesis, wood density, and tensile strength. Leaf explants are harvested from stock Eucalyptus plants and the explants are cultured on a pre-treatment medium. The pre-culture medium comprises auxin, cytokinin, and an Agrobacterium inducer, such as acetosyringone, to stimulate cell division along the excised edges of the tissue explant. Following four days of pre-culture, the expiants are inoculated with Agrobacterium strain GV2260 containing a plasmid bearing a portion of the UDP-glucose binding domain operably linked to a ubiquitin promoter. The

explants are co-cultivated for 3 days prior to transfer to Euc Regeneration medium. The explants are cultured on Eucalyptus Regeneration medium for 4 days before transfer to selection medium containing an herbicide. [476] Following the selection of herbicide-resistant transformants, the transformants are assayed for GUS expression. Upon the confirmation of GUS expression, shoots are harvested and transferred to a rooting medium. The rooting medium comprises BTM-1 salts supplemented with 5g/l MeadWestvaco Nuchar activated carbon, and rooting development usually occurs after 2-4 weeks. Upon development of the primary root system, the transformed plants are transferred to soil. The transgenic Eucalyptus plants carrying any one of SEQ ID NOs. 1-197 operably linked to a ubiquitin promoter exhibit modulated growth rates, responses to environmental cues and altered phenotypic traits.

Example 3

[477] Example 3 illustrates a procedure for RNA extraction and purification, which is particularly useful for RNA obtained from conifer needle, xylem, cambium, and phloem.

[478] Tissue is obtained from conifer needle, xylem, cambium or phloem. The tissue is frozen in liquid nitrogen and ground. The total RNA is extracted using Concert Plant RNA reagent (Invitrogen). The resulting RNA sample is extracted into phenokchloroform and treated with DNase. The RNA is then incubated at 65 0 C for 2 minutes followed by centrifugation at 4 0 C for 30 minutes. Following centrifugation, the RNA is extracted into phenol at least 10 times to remove contaminants.

[479] The RNA is further cleaned using RNeasy columns (Qiagen). The purified RNA is quantified using RiboGreen reagent (Molecular Probes) and purity assessed by gel electrophoresis.

[480] RNA is then amplified using MessageAmp (Ambion). Aminoallyl-UTP and free UTP are added to the in vitro transcription of the purified RNA at a ratio of 4:1 aminoallyl-UTP-to-UTP. The aminoallyl-UTP is incorporated into the new RNA strand as it is transcribed. The amino-allyl group is then reacted

with Cy dyes to attach the colorimetric label to the resulting amplified RNA using the Amersham procedure modified for use with RNA. Unincorporated dye is removed by ethanol precipitation. The labeled RNA is quantified spectrophotometrically (NanoDrop). The labeled RNA is fragmented by heating to 95 0 C as described in Hughes et al., Nature Biotechnol. 19:342 (2001).

Example 4

[481] Example 4 illustrates how cell signaling genes important for wood development in P. radiata can be determined and how oligonucleotides which uniquely bind to those genes can be designed and synthesized for use on a microarray.

[482] Pine trees of the species P. radiata are grown under natural light conditions. Tissue samples are prepared as described in, e.g., Sterky et al., Proc. Nat'l Acad. ScL 95:13330 (1998). Specifically, tissue samples are collected from woody trees having a height of 5 meters. Tissue samples of the woody trees are prepared by taking tangential sections through the cambial region of the stem. The stems are sectioned horizontally into sections ranging from juvenile (top) to mature (bottom). The stem sections separated by stage of development are further separated into 5 layers by peeling into sections of phloem, differentiating phloem, cambium, differentiating xylem, developing xylem, and mature xylem. Tissue samples, including leaves, buds, shoots, and roots are also prepared from seedlings of the species P. radiata.

[483] RNA is isolated and ESTs generated as described in Example 1 or Sterky et al., supra. The nucleic acid sequences of ESTs derived from samples containing developing wood are compared with nucleic acid sequences of genes known to be involved in cell signaling. ESTs from samples that do not contain developing wood are also compared with sequences of genes known to be involved in the plant growth and development. An in silico hybridization analysis can then be performed using BLAST (NCBI).

[484] Sequences from among the known cell signaling genes that show hybridization in silico to ESTs made from samples containing developing wood, but that do not hybridize to ESTs from samples not containing developing wood are selected for further examination. [485] cDNA clones containing sequences that hybridize to the genes showing wood-preferred expression are selected from cDNA libraries using techniques well known in the art of molecular biology. Using the sequence information, oligonucleotides are designed such that each oligonucleotide is specific for only one cDNA sequence in the library. The oligonucleotide sequences are provided in TABLE 4. 60-mer oligonucleotide probes are designed using the method of Li and Stormo, supra or using software such as ArrayDesigner, GeneScan, and ProbeSelect.

[486] The oligonucleotides are then synthesized in situ described in Hughes et al., Nature Biotechnol. 19:324 (2002) or as described in Kane et al., Nucleic Acids Res. 28:4552 (2000) and affixed to an activated glass slide (Sigma- Genosis, The Woodlands, TX) using a 5' amino linker. The position of each oligonucleotide on the slide is known.

Example 5

[487] Example 5 illustrates how RNAs of tissues from multiple pine species, in this case both P. radiata and loblolly pine P. taeda trees, are selected for analysis of the pattern of gene expression associated with wood growth and development in the juvenile wood and mature wood forming sections of the trees using the microarrays derived from P. radiata cDNA sequences described in Example 4.

[488] Open pollinated trees of approximately 16 years of age are selected from plantation-grown sites, in the United States for loblolly pine, and in New Zealand for radiata pine. Trees are felled during the spring and summer seasons to compare the expression of genes associated with these different developmental stages of wood formation. Trees are felled individually and trunk sections are removed from the bottom area approximately one to two meters from the base and within one to two meters below the live crown. The

section removed from the basal end of the trunk contains mature wood. The section removed from below the live crown contains juvenile wood. Samples collected during the spring season are termed earlywood or springwood, while samples collected during the summer season are considered latewood or summerwood. Larson et al., Gen. Tech. Rep. FPL-GTR-129. Madison, Wl: U.S. Department of Agriculture, Forest Service, Forest Products Laboratory, p. 42.

[489] Tissues are isolated from the trunk sections such that phloem, cambium, developing xylem, and maturing xylem are removed. These tissues are collected only from the current year's growth ring. Upon tissue removal in each case, the material is immediately plunged into liquid nitrogen to preserve the nucleic acids and other components. The bark is peeled from the section and phloem tissue removed from the inner face of the bark by scraping with a razor blade. Cambium tissue is isolated from the outer face of the peeled section by gentle scraping of the surface. Developing xylem and lignifying xylem are isolated by sequentially performing more vigorous scraping of the remaining tissue. Tissues are transferred from liquid nitrogen into containers for long term storage at -70 0 C until RNA extraction and subsequent analysis is performed.

Example 6

[490] Example 6 illustrates procedures alternative to those used in Example 3 for RNA extraction and purification, particularly useful for RNA obtained from a variety of tissues of woody plants, and a procedure for hybridization and data analysis using the arrays described in Example 4. [491] RNA is isolated according to the protocol of Chang et al., Plant MoI. Biol. Rep. 77:113-116 (1993). DNA is removed using DNase I (Invitrogen, Carlsbad, CA) according to the manufacturer's recommendations. The integrity of the RNA samples is determined using the Agilent 2100 Bioanalyzer (Agilent Technologies, USA).

[492] 10μg of total RNA from each tissue is reverse transcribed into cDNA using known methods.

[493] In the case of Pinus radiata phloem tissue, it can be difficult to extract sufficient amounts of total RNA for normal labelling procedures. Total RNA is extracted and treated as previously described and 100ng of total RNA is amplified using the Ovation™ Nanosample RNA Amplification system from

NuGEN™ (NuGEN, CA, USA). Similar amplification kits such as those manufactured by Ambion may alternatively be used. The amplified RNA is reverse transcribed into cDNA and labelled as described above.

[494] Hybridization and stringency washes are performed using the protocol as described in the US Patent Application for "Methods and Kits for Labeling and Hybridizing cDNA for Microarray Analysis" (supra) at 42 C. The arrays

(slides) are scanned using a ScanArray 4000 Microarray Analysis System

(GSI Lumonics, Ottawa, ON, Canada). Raw, non-normalized intensity values are generated using QUANTARRAY software (GSI Lumonics, Ottawa, ON,

Canada).

[495] A fully balanced, incomplete block experimental design (Kerr and

Churchill, Gen. Res. 123:123, 2001) is used in order to design an array experiment that would allow maximum statistical inferences from analyzed data.

[496] Gene expression data is analyzed using the SAS® Microarray Solution software package (The SAS Institute, Cary, NC, USA). Resulting data was then visualized using JMP® (The SAS Institute, Cary, NC, USA).

[497] Analysis done for this experiment is an ANOVA approach with mixed model specification (Wolfinger et al., J. Comp. Biol. 8:625-637). Two steps of linear mixed models are applied. The first one, normalization model, is applied for global normalization at slide-level. The second one, gene model, is applied for doing rigorous statistical inference on each gene. Both models are stated in Models (1) and (2).

logj iY≠ls ) = θi j + £> k + S 1 + DS k , + ω ≠ls (1)

*$ = 4 8) + D i s) + s > 8) + DS if + ss i s) + 4ll &

[498] Yijkis represents the intensity of the s th spot in the I th slide with the k th dye applying the j th treatment for the i th cell line, θy, D k , Si, and D Sk i represent the mean effect of the jth treatment in the ith cell line, the kth dye effect, the I th slide random effect, and the random interaction effect of the k th dye in the I th slide, (jϋij k is is the stochastic error term, represent the similar roles as θy, D k , Si, and Dski except they are specific for the g th gene. R$ S represents the residual of the g th gene from model (1). and DS$ represent the similar roles as θ,y, D k , Si, and DSM except they are specific for the g th gene. ssjf ) represent the spot by slide random effect for the g th gene, εfβl represent the stochastic error term. All random terms are assumed to be normal distributed and mutually independent within each model. [499] According to the analysis described above, certain cDNAs can be shown to be differentially expressed.

[500] The involvement of these specific genes in wood growth and development is inferred through the association of the up-regulation or down- regulation of genes to the particular stages of wood development. Both the spatial continuum of wood development across a section (phloem, cambium, developing xylem, maturing xylem) at a particular season and tree trunk position and the relationships of season and tree trunk position should be considered when making associations of gene expression to the relevance in wood development.

Example 7

[501] Example 7 demonstrates how one can correlate cell signaling gene expression with agronomically important wood phenotypes such as density, stiffness, strength, distance between branches, and spiral grain. [502] Mature clonally propagated pine trees are selected from among the progeny of known parent trees for superior growth characteristics and resistance to important fungal diseases. The bark is removed from a tangential section and the trees are examined for average wood density in the fifth annual ring at breast height, stiffness and strength of the wood, and spiral

grain. The trees are also characterized by their height, mean distance between major branches, crown size, and forking.

[503] To obtain seedling families that are segregating for major genes that affect density, stiffness, strength, distance between branches, spiral grain and other characteristics that may be linked to any of the genes affecting these characteristics, trees lacking common parents are chosen for specific crosses on the criterion that they exhibit the widest variation from each other with respect to the density, stiffness, strength, distance between branches, and spiral grain criteria. Thus, pollen from a tree exhibiting high density, low mean distance between major branches, and high spiral grain is used to pollinate cones from the unrelated plus tree among the selections exhibiting the lowest density, highest mean distance between major branches, and lowest spiral grain. It is useful to note that "plus trees" are crossed such that pollen from a plus tree exhibiting high density are used to pollinate developing cones from another plus tree exhibiting high density, for example, and pollen from a tree exhibiting low mean distance between major branches would be used to pollinate developing cones from another plus tree exhibiting low mean distance between major branches.

[504] Seeds are collected from these controlled pollinations and grown such that the parental identity is maintained for each seed and used for vegetative propagation such that each genotype is represented by multiple ramets. Vegetative propagation is accomplished using micropropagation, hedging, or fascicle cuttings. Some ramets of each genotype are stored while vegetative propagules of each genotype are grown to sufficient size for establishment of a field planting. The genotypes are arrayed in a replicated design and grown under field conditions where the daily temperature and rainfall are measured and recorded.

[505] The trees are measured at various ages to determine the expression and segregation of density, stiffness, strength, distance between branches, spiral grain, and any other observable characteristics that may be linked to any of the genes affecting these characteristics. Samples are harvested for

characterization of cellulose content, lignin content, cellulose microfibril angle, density, strength, stiffness, tracheid morphology, ring width, and the like. Samples are also examined for gene expression as described in Example 6. Ramets of each genotype are compared to ramets of the same genotype at different ages to establish age:age correlations for these characteristics.

Example 8

[506] Example 8 demonstrates how responses to environmental conditions such as light and season alter plant phenotype and can be correlated to cell signaling gene expression using microarrays. In particular, the changes in gene expression associated with wood density are examined. [507] Trees of three different clonally propagated E. grandis hybrid genotypes are grown on a site with a weather station that measures daily temperatures and rainfall. During the spring and subsequent summer, genetically identical ramets of the three different genotypes are first photographed with north-south orientation marks, using photography at sufficient resolution to show bark characteristics of juvenile and mature portions of the plant, and then felled. The age of the trees is determined by planting records and confirmed by a count of the annual rings. In each of these trees, mature wood is defined as the outermost rings of the tree below breast height, and juvenile wood as the innermost rings of the tree above breast height. Each tree is accordingly sectored as follows:

NWI - NORTHSIDE MATURE

SM - SOUTHSIDE MATURE

NT - NORTHSIDE TRANSITION

ST - SOUTHSIDE TRANSITION

NJ - NORTHSIDE JUVENILE

SJ - SOUTHSIDE JUVENILE

[508] Tissue is harvested from the plant trunk as well as from juvenile and mature form leaves. Samples are prepared simultaneously for phenotype analysis, including plant morphology and biochemical characteristics, and gene expression analysis. The height and diameter of the tree at the point

from which each sector was taken is recorded, and a soil sample from the base of the tree is taken for chemical assay. Samples prepared for gene expression analysis are weighed and placed into liquid nitrogen for subsequent preparation of RNA samples for use in the microarray experiment. The tissues are denoted as follows:

P - phloem

C - cambium

X1 - expanding xylem

X2 - differentiating and lignifying xylem

[509] Thin slices in tangential and radial sections from each of the sectors of the trunk are fixed as described in Ruzin, Plant Microtechnique and Microscopy, Oxford University Press, Inc., New York, NY (1999) for anatomical examination and confirmation of wood developmental stage. Microfibril angle is examined at the different developmental stages of the wood, for example juvenile, transition and mature phases of Eucalyptus grandis wood. Other characteristics examined are the ratio of fibers to vessel elements and ray tissue in each sector. Additionally, the samples are examined for characteristics that change between juvenile and mature wood and between spring wood and summer wood, such as fiber morphology, lumen size, and width of the S2 (thickest) cell wall layer. Samples are further examined for measurements of density in the fifth ring and determination of modulus of elasticity using techniques well known to those skilled in the art of wood assays. See, e.g., Wang, et al., Non-destructive Evaluations of Trees, Experimental Techniques, pp. 28-30 (2000).

[510] For biochemical analysis, 50 grams from each of the harvest samples are freeze-dried and analyzed, using biochemical assays well known to those skilled in the art of plant biochemistry for quantities of simple sugars, amino acids, lipids, other extractives, lignin, and cellulose. See, e.g., Pettersen & Schwandt, J. Wood Chem. & Technol. 11 :495 (1991). [511] In the present example, the phenotypes which can be chosen for comparison are high density wood, average density wood, and low density

wood. Nucleic acid samples are prepared as described in Example 3, from trees harvested in the spring and summer. Gene expression profiling by hybridization and data analysis is performed as described above. [512] Using similar techniques and clonally propagated individuals one can examine cell signaling gene expression as it is related to other complex wood characteristics such as strength, stiffness and spirality.

Example 9

[513] Example 9 demonstrates how a cell signaling gene can be linked to a tissue-preferred promoter and expressed in pine.

[514] A cell signaling gene, which is more highly expressed during the early spring, is identified by the method described in Example 7. A DNA construct having the density-related polypeptide operably linked to a promoter is placed into an appropriate binary vector and transformed into pine using the methods described herein. Pine plants are transformed as described in herein and the transgenic pine plants are used to establish a forest planting. Increased density even in the spring wood (early wood) is observed in the transgenic pine plants relative to control pine plants which are not transformed with the density related DNA construct.

Example 10

[515] Using techniques well known to those skilled in the art of molecular biology, the sequence of a cell signalling gene isolated in Example 9 can be analyzed in genomic DNA isolated from alfalfa. This enables the identification of an orthologue in alfalfa. The orthologue nucleotide sequence can then be used to create an RNAi knockout construct. This construct is then transformed into alfalfa. See, e.g., Austin et a/.,. Euphytica 85, 381 (1995). The regenerated transgenic plants should demonstrate modulated growth, development or a perturbed ability to perceive and respond to environmental cues.

Example 11

[516] Example 11 demonstrates how gene expression analysis can be used to find gene variants which are present in mature plants having a desirable phenotype. The presence or absence of such a variant can be used to predict the phenotype of a mature plant, allowing screening of the plants at the seedling stage. Although this example employs eucalyptus, the method used herein is also useful in breeding programs for pine and other tree species. [517] The sequence of a putative density-related gene is used to probe genomic DNA isolated from Eucalyptus that vary in density as described in previous examples. Non-transgenically produced Eucalyptus hybrids of different wood phenotypes are examined. One hybrid exhibits high wood density and another hybrid exhibits lower wood density. A molecular marker in the 3' portion of the coding region is found which distinguishes a high- density gene variant from a lower density gene variant. [518] This molecular marker enables tree breeders to assay non-transgenic Eucalyptus hybrids for likely density profiles while the trees are still at seedling stage, whereas in the absence of the marker, tree breeders must wait until the trees have grown for multiple years before density at harvest age can be reliably predicted. This enables selective outplanting of the best trees at seedling stage rather than an expensive culling operation and resultant erosion at thinning age. This molecular marker is further useful in the breeding program to determine which parents will give rise to high density outcross progeny.

[519] Molecular markers located in the 3' portion of the coding region of the gene that do not correspond to variants seen more frequently in higher or lower wood density non-transgenic Eucalyptus hybrid trees are also useful for fingerprinting different genotypes of Eucalyptus, for use in identity-tracking in the breeding program and in plantations.

Example 12

[520] This Example describes microarrays for identifying gene expression differences that contribute to the phenotypic characteristics that are important in commercial wood, namely wood appearance, stiffness, strength, density,

fiber dimensions, coarseness, cellulose and lignin content, extractives content and the like.

[521] Woody trees of genera that produce commercially important wood products, in this case Pinυs and Eucalyptus, are felled from various sites and at various times of year for the collection and isolation of RNA from developing xylem, cambium, phloem, leaves, buds, roots, and other tissues. RNA is also isolated from seedlings of the same genera. [522] All contigs are compared to both the ESTs made from RNA isolated from samples containing developing wood and the sequences of the ESTs made from RNA of various tissues that do not contain developing wood. Contigs containing primarily ESTs that show more hybridization in silico to ESTs made from RNA isolated from samples containing developing wood than to ESTs made from RNA isolated from samples not containing developing wood are determined to correspond to possible novel genes particularly expressed in developing wood. These contigs are then used for BLAST searches against public domain sequences. Those contigs that hybridize in silico with high stringency to no known genes or genes annotated as having only a "hypothetical protein" are selected for the next step. These contigs are considered putative novel genes showing wood-preferred expression.

[523] The longest cDNA clones containing sequences hybridizing to the putative novel genes showing wood-preferred expression are selected from cDNA libraries using techniques well known to those skilled in the art of molecular biology. The cDNAs are sequenced and full-length gene-coding sequences together with untranslated flanking sequences are obtained where possible. Stretches of 45-80 nucleotides (or oligonucleotides) are selected from each of the sequences of putative novel genes showing wood-preferred expression such that each oligonucleotide probe hybridizes at high stringency to only one sequence represented in the ESTs made from RNA isolated from trees or seedlings of the same genus.

[524] Oligomers are then chemically synthesized and placed onto a microarray slide as described in Example 4. Each oligomer corresponds to a particular sequence of a putative novel gene showing wood-preferred expression and to no other gene whose sequence is represented among the ESTs made from RNA isolated from trees or seedlings of the same genus. [525] Sample preparation and hybridization are carried out as in Example 4. The technique used in this example is more effective than use of a microarray using cDNA probes because the presence of a signal represents significant evidence of the expression of a particular gene, rather than of any of a number of genes that may contain similarities to the cDNA due to conserved functional domains or common evolutionary history. Thus, it is possible to differentiate homologous genes, such as those in the same family, but which may have different functions in phenotype determination. [526] This hybridization data, gained using the method of Example 6, enables the user to identify which of the putative novel genes actually possesses a pattern of coordinate expression with known genes, a pattern of expression consistent with a particular developmental role, and/or a pattern of expression that suggests that the gene has a promoter that drives expression in a valuable way.

[527] The hybridization data obtained using this method can be used, for example, to identify a putative novel gene that shows an expression pattern particular to the tracheids with the lowest cellulose microfibril angle in developing spring wood (early wood). The promoter of this gene can also be isolated as in Example 8, and operably linked to a gene that has been shown as in Example 9 to be associated with late wood (summer wood). Transgenic pine plants containing this construct are generated using the methods of Example 9, and the early wood of these plants is then shown to display several characteristics of late wood, such as higher microfibril angle, higher density, smaller average lumen size, etc.

Example 13

[528] Example 13 demonstrates the use of a xylem-specific promoter functionally linked to a cell signaling gene for increased plant growth. [529] Xylem-specific cell signaling gene products are identified via array analyses of different secondary vasculature layers as described in Example 6. Candidate promoters linked to the genes corresponding to these gene products are cloned from pine genomic DNA using, e.g., the BD Clontech GenomeWalker kit and tested in transgenic tobacco via a reporter assay(s) for cambium specificity/preference. A promoter which overexpresses a gene in xylem can be chosen. The promoter is operably linked to a cell signaling gene and the DNA construct is used to transform a plant. Boosted transcript levels of candidate cell signaling genes, aberrant cell signaling enzyme activity, and modulated growth and development may result in an increase of cell growth thereby increasing xylem-biomass.

Example 14

[530] Example 14 describes the construction strategy and assembly of DNA constructs comprising cell signaling genes.

[531] The DNA construct pWVR202 was used as the base cloning vector for 16 cell signaling gene DNA constructs. The nucleotide sequence of pVWR202 is depicted in TABLE 7 as SEQ ID NO: 584 and graphically shown in FIGURE 198. pWVR202 is a modified Ti plasmid comprising a polynucleotide with LB, RB, and nopaline synthase elements. pWVR202 comprises two neomycin phosphotransferase genes, nptll and nptlll, as selectable markers. It also comprises a chimeric Pinus radiata superubiquitin promoter and intron (SUBIN) operably linked to a polylinker sequence. The SUBIN promoter was previously described in U.S. Patent No. 6,380,459 and identified therein as SEQ ID NO: 2. The pWVR202 polylinker comprises a polynucleotide sequence possessing the recognition sites of the restriction endonucleases Pstl, Nhel, Avrll, Seal and CIaI.

[532] The pGrowth DNA constructs were assembled by one of two cloning strategies. First, the target gene is excised from the source polynucleotide by a restriction endonuclease causing the resulting polynucleotide fragment to

have blunt ends. Such a fragment is cloned into the Seal restriction endonuclease recognition site. Alternatively, the ends of any polynucleotide fragment can be polished and inserted at the Seal site. Second, some target polynucleotides were excited by the Spel restriction endonuclease and inserted into pWVR202 digested by both the Avrll and Nhel restriction endonucleases. Those skilled in the art can easily develop other cloning strategies using site-specific endonucleases and other enzymes known in the art. Once complete, the DNA constructs were verified by extensive restriction digests to ensure proper assembly.

[533] Twelve pGrowth DNA constructs comprising cell signaling genes were assembled. TABLE 8 lists the DNA construct, the purported cell signaling gene and the gene SEQ ID NO.

TABLE 8: pGrowth Cell Signaling Gene DNA Constructs

[534] These DNA constructs are depicted in FIGURES 199-210 and 212- 215..

Example 15

[535] Example 15 demonstrates the transformation of Populus deltoids with some of the DNA constructs of Example 14.

[536] The DNA constructs described in Example 14 were used to transform Populus deltoides stock plant cultures. The DNA constructs used were pGrowthi , pGrowth2, pGrowth3, pGrowthi l , pGrowth21 , pGrowth22, pGrowth23, pGrowth24, pGrowth25, pGrowth26, pGrowth27, pGrowth28, pGrowth29, and pGrowth30. The DNA construct pWVRδ comprising the gus gene acted as a negative control for subsequent experiments. See Gleave, Plant MoI. Biol. 20:1203-27 (1992), Wesley et al., Plant J. 27(6):581-90 (2001). Each DNA construct was inoculated into Agrobacterium cultures by standard techniques.

[537] Populus deltoides stock plant cultures were maintained on DKW medium (see, e.g., Driver and Kuniyuki, HortScience 19 (4,):507-509 (1984)) with about 2.5 uM zeatin in a growth room with an approximately 16 hour photoperiod. For transformation, petioles were excised aseptically using a sharp scalpel blade from the stock plants, cut into lengths from about 4 mm to about 6 mm, placed on DKW medium with about 1 ug/ml BAP and about 1 ug/ml NAA immediately after harvest, and incubated in a dark growth chamber at about 28 0 C for about 24 hours.

[538] Agrobacterium cultures were grown to log phase, as indicated by an OD 6 Oo from about 0.8 to about 1.0 A. Cultures were then pelleted and resuspended in an equal volume of Agrobacterium Induction Medium (AIM) containing Woody Plant Medium salts (Lloyd and McCown, Combined Proceedings of the International Plant Propagators Society 30:421-427 (1980)), about 5 g/L glucose, about 0.6 g/L MES at about pH 5.8, and about 1 μl_ of a 100 mM stock solution of acetosyringone per ml of AIM. The Agrobacterium pellet was resuspended by vortexing. Bacterial cells were incubated for an about an hour at about 28°C in an environmental chamber while being shakien at about 100 rpm.

[539] Subsequently, P. deltoides explants were exposed to the Agrobacterium mixture for approximately 15 minutes. The explants were then lightly blotted on sterile paper towels, replaced onto the same plant medium and cultured in the dark at about 18°C to about 2O 0 C. After a three-day co-

cultivation period, the explants were transferred to DKW medium in which the NAA concentration was reduced to about 0.1 ug/ml and to which was added about 400 mg/L timentin.

[540] After approximately 4 days on eradication medium, explants were transferred to small magenta boxes containing the same medium supplemented with timentin (400mg/L) as well as the selection agent geneticin (50 mg/L). Explants were transferred every two weeks to fresh selection medium. CaIIi that grow in the presence of the selection medium were isolated and sub-cultured to fresh selection medium every three weeks. CaIIi were observed for the production of adventitious shoots. [541] Adventitious shoots were normally observed within two months from the initiation of transformation. These shoot clusters were transferred to DKW medium to which no NAA was added, and in which the BAP concentration was reduced to 0.5 ug.ml. This medium was designed for shoot elongation to occur over a period of about 14 weeks. Subsequently, elongated shoots were excised and transferred to BTM medium (see Chalupa, Communicationes lnstituti Forestalls Checosloveniae 13:7-39, (1983)) at about pH5.8 and containing about 20 g/l sucrose and about 5 g/l activated charcoal. The complete BTM-1 formula is set forth in TABLE 9. This medium facilitates the development of roots.

TABLE 9: Exemplary Rooting Medium for Populus deltoides

[542] After development of roots, which typically occurs in about 4 weeks, transformants were propagated in a greenhouse by rooted cutting methods or in vitro through auxiliary shoot induction. In the later case, transformants were grown for about four weeks on DKW medium containing about 11.4 μM zeatin. Subsequently, the multiplied shoots from each transformant line were separated and transferred to root induction medium (each plant of a line is a ramet). Rooted plants were transferred to soil for evaluation of growth in glasshouse and field conditions.

Example 16

[543] Example 16 demonstrates the modulation of adventitious shoots in the transformed plants of Example 15.

[544] Approximately 100 explants of P. deltoides were transformed by the method of Example 15 with each of the DNA constructs described in Example

14 (except pGrowthi, pGrowth2, pGrowth3, pGrowth29, pGrowth49 and pGrowth51). A number of explants transformed with pGrowth22, pGrowth25 and pGrowth30 were found to provide shoots of a size that were already transferable to rooting medium at only 12 weeks after transformation. TABLE 10 demonstrates the regenerative capability of the transformants.

TABLE 10: Exemplary Growth Data for Cell Signal Gene Transformants

[545] Briefly, calli produced on petiole explants are observed regularly. As shoots formed, they were transferred to shoot elongation medium. Sufficiently healthy and elongated shoot lines were transferred to rooting medium as they became ready. Only transformants comprising pGrowth22, pGrowth25 and pGrowth30 were found to possess a phenotype characterized by rapid regeneration.

[546] At 3 months, neither the other transformants nor the control transformant had produced shoot lines that were ready to be collected for rooting. Cultures of the pGrowth22, pGrowth25 and pGrowth30 transformants, however, were ready to be moved to rooting medium. FIGURE 211 shows the percent of shoot lines from each transformant which were ready to be placed in rooting medium. TABLE 10 demonstrates that the regeneration-enhancing effect of the putative cell signaling genes was not due to increased transformation efficiency, although pGrowth25 appears to have raised transformation efficiency relative to the control and the other plasmids.

[547] Likewise, TABLE 11 shows the subsequent growth of the transformants. First, TABLE 11 demonstrates the regeneration of the other transformants and control plants within 5 months. Second, TABLE 11 illustrates that the characteristic of the pGrowth22, pGrowth25 and pGrowth30 transformants was, in fact, accelerated regeneration and not an increase in the total number of shoot lines produced.

TABLE 11 : Exemplary Growth Data for Cell Signal Gene Transformants

[548] P. deltoides is a model species representing a variety of commercially important angiosperm species useful for the testing of the effect of cell signaling genes and gene products on plant growth and development. Regeneration of plantlets from cottonwood callus cultures produced by transformation is a rate-limiting step for the establishment of plants in outdoor field tests. In this example, the control plant did not produce any shoot lines ready for transfer to rooting medium until 5 months after transformation. An acceleration of two months could, in certain seasons, significantly advance the establishment of transgenic plants. In certain seasons, up to a year of growth can be saved using the pGrowth22, pGrowth25 and pGrowth30 transformants.

Example 17

[549] Example 17 demonstrated the qualitative and quantitative modulation of plant leaves in the transformed plants of Example 15.

[550] P. deltoids plants were transformed with the DNA construct pGrowth24 by the method of Example 15. The pGrowth24 DNA construct ectopically overexpresses a putative 14-3-3 protein disclosed as SEQ ID NO: 192. The cloning strategy and assembly of pGrowth24 is described in Example 14. Negative control plants were transformed with the GUS expressing DNA construct pWVR8 described in Gleave, Plant MoI. Biol. 20:1203-27 (1992) and Wesley et al., Plant J. 27^:581-90 (2001).

[551] Upon regeneration, the pGrowth24-transformed plants presented an aberrant phenotype as compared to the negative control plants. Specifically, the transformants presented particularly narrow leaves in tissue culture. Ramlets generated in tissue culture continued to present this narrow leaf phenotype. After the ramlets were transferred from tissue culture to hormone- free BTM rooting medium, the narrow leaf phenotype persisted. [552] The transformants' leaves are exceptionally narrow as compared to the negative control. However, the length of the transformants' leaves were qualitatively similar to those of the negative control plants. Lastly, the transformants presented a qualitative increase in the number of leaves per plant as compared to a negative control plant of the same height (i.e., an increase of leaves per unit plant height).

[553] Accordingly, by qualitatively and quantitatively modulating leaf surface area, the DNA constructs may alter the capacity of a plant for photosynthesis.

Example 18

[554] Example 18 demonstrates the qualitative and quantitative modulation of stem growth and development in the transformed plants of Example 15. [555] P. deltoids plants were transformed with the DNA construct pGrowth25 by the method of Example 15. The pGrowth25 DNA construct ectopically overexpresses a putative synaptobrevin-like protein disclosed as SEQ ID NO: 98. The cloning strategy and assembly of pGrowth25 is described in Example 14. Negative control plants were transformed with the GUS expressing DNA construct pWVRδ described in Gleave, Plant MoI. Biol. 20:1203-27 (1992) and Wesley et al., Plant J. 27(6J:581-90 (2001).

[556] The transformants' presented unusually rapid regeneration as compared to the negative control plants. In addition, the transformants presented a qualitative and quantitative difference in stem growth. First, the transformants appeared to growth faster and longer compared to the negative control plants. Second, transformants presented quantitatively longer internodes than the negative control plants.

[557] The modulation of internode length is commercially significant for the commercial forestry industry. In woody plants, stem nodes subtend potential branch. Branches, themselves, form a locus for undesirable traits such as knot formation and the deposition of compression wood. Both traits reduce the utility of the woody plant for pulp and solid wood products. [558] Accordingly, by qualitatively and quantitatively modulating stem growth, the DNA constructs may alter the utility of the plant for the commercial forestry industry.

Example 19

[559] Example 19 demonstrates the qualitative modulation of stem growth and development in the transformed plants of Example 15. [560] P. deltoids plants were transformed with the DNA construct pGrowth27 by the method of Example 15. The pGrowth27 DNA construct ectopically overexpresses a putative synaptobrevin-like protein disclosed as SEQ ID NO: 155. The cloning strategy and assembly of pGrowth25 is described in Example 14. Negative control plants were transformed with the GUS expressing DNA construct pWVR8 described in Gleave, Plant MoI. Biol. 20:1203-27 (1992) and Wesley et al., Plant J. 27^:581-90 (2001). [561] The transformants presented longitudinal invaginations of the stem. These invaginations are characterized as striations in the stem longitudinal architecture. As such, the transformants possessed stems which appeared either "corrugated" or possessing callus under the epidermis. From these observations, it appeared that the rate of cell division in the radial and/or tangential plane in the stem was exceeding the rate of tangential cell expansion. As the transformants grew, the stem striations became more

pronounced. Likewise, the growth remained stem specific in all but one transformant. In that case, the plant leaves were unusually rounded convoluted across the face of the leaf. It is thought that both phenotypic characteristics result from an increase in cell division. [562] Synaptobrevins/vesicle-associated membrane proteins (VAMPs) together with syntaxins and a synaptosome-associated protein of 25 kDa (SNAP-25) are the main components of a protein complex involved in the docking and/or fusion of synaptic vesicles with the presynaptic membrane in Saccharomyces cerevisiae. It appears that the gene is conserved among eukaryotes, but its function in higher plants is as yet unknown. These observations represent the first description of a phenotype in plants produced by these genes.

[563] To the commercial forestry industry, the striation phenotype has significant potential utility. It is believed that the striations are an indication of greater cell division rates in diameter growth. Striations are commonly seen in cottonwood on older, more mature stems. In contrast, newly emerging, succulent stems, such as those present in tissue culture, are smooth and cylindrical. It is believed that new, succulent shoots may be smooth for up to 3 feet from their distal/apical end to the point where striations begin to form. Striations seem to be associated with stems of larger diameter, for instance ones that are greater than 1 inch in circumference.

[564] Moreover, this phenotype may indicate a quantitative increase in the density of stems and branches. This increased density and longitudinal thickening can provide additional support for the plant. In woody plants, species presenting longitudinal striations are more likely to form in waterlogged soils. It is thought that the increased striation phenotype described here is indicative of transformants adapted for soils in which less stable trees can topple.

Example 20

[0565] Example 20 demonstrated the effect of cell signaling genes on growth in the transformed plants of Example 15.

[0566JP. deltoids plants were transformed with the DNA constructs pGrowth2, pGrowth3, pGrowthH , pGrowth21, pGrowth22, pGrowth23, pGrowth24, pGrowth25, pGrowth26, pGrowth27, pGrowth28 and pGrowth30 by the method of Example 15. Negative control plants were transformed with the GUS expressing DNA construct pWVRδ described in Gleave, Plant MoI. Biol. 20:1203-27 (1992) and Wesley et al., Plant J. 27(6J:581-90 (2001).

[0567] Rooted plants made by the method described in Example 15 were transferred to a mist house for between 10 days and 2 weeks to facilitate acclamation. Misting conditions varied depending on outside environmental conditions. Plants were then grown in standard greenhouse conditions for 2.5 to 3 months before being moved to outdoor conditions for between 7 to 10 days for hardening.

[0568] Four ramets for each line and the control were then planted in a field trial in a randomized block design. After 7 months of growth, plant height and diameter were measured to calculate the volume or biomass of the trees. Height was measured between the root collar and the terminal bud, while diameter was taken at breast height (4.5 feet) (Diameter at Breast Height = DBH). The volume index was calculated by multiplying the square of the DBH by the height. All subsequent growth measurements are a comparison of the volume index calculated as described above.

[0569] Plants transformed with pGrowth2 or pGrowth3 were measured after 14 months of growth, while plants transformed with pGrowthH , pGrowth21 , pGrowth22, pGrowth23, pGrowth24, pGrowth25, pGrowth26, pGrowth27, pGrowth28 and pGrowth30 were measured after 18 months of growth. For example, after 18 months of growth plants transformed with pGrowth11 , pGrowth21 , pGrowth24, pGrowth25, pGrowth26, pGrowth27, and pGrowth30 did not demonstrate overall growth increases over the GUS control plants, but did generate rapidly growing lines with volume growth increases exceeding 50%. These lines with growth increases exceeding 50% result in their being a shift in the population and thus an increase of the volume in the top elite plants within that population compared to the top elite

plants of the control. It was observed that one out of 8 lines (13%) of construct pGrowth11 had growth increases exceeding 50%; the growth increase of this line was 100%. Four out of 15 lines (27%) of construct pGrowth21 had growth increases exceeding 50%; growth increases of these lines were 96%, 84%, 79%, and 54%. One out of 9 lines (11%) of construct pGrowth24 had growth increases exceeding 50%; the growth increase of this line was 55%. Two out of 27 lines (7%) of construct pGrowth25 had growth increases exceeding 50%; growth increases of these lines were 110% and 94%. One out of 8 lines (13%) of construct pGrowth26 had growth increases exceeding 50%; the growth increase of this line was 75%. Two out of 28 lines (7%) of construct pGrowth27 had growth increases exceeding 50%; growth increases of these lines were 98% and 88%. One out of 13 lines (8%) of construct pGrowth30 had growth increases exceeding 50%; the growth increase of this line was 117%. Table 12 summarises the results for the putative cell signaling genes that were transformed into P. deltoids plants.

Table 12: Exemplry growth data for cell signaling gene in P. deltoids transformants

Example 21

[570] Example 21 demonstrates the modulation of plant growth and development by the modulation of the programmed cell death (PCD) signaling cascade.

[571] P. deltoids plants were transformed with the DNA constructs pGrowthi and pGrowth2 by the method of Example 15. The pGrowthi DNA construct ectopically overexpresses a putative polyphosphoinositide binding protein disclosed as SEQ ID NO: 130. The cloning strategy and assembly of pGrowthi is described in Example 14. The pGrowth2 DNA construct ectopically overexpresses a putative polyphosphoinositide binding protein SSH2P disclosed as SEQ ID NO: 132. The cloning strategy and assembly of pGrowth2 is described in Example 14. Negative control plants were transformed with the GUS expressing DNA construct pWVRδ described in Gleave, Plant MoI. Biol. 20:1203-27 (1992) and Wesley et al., Plant J. 27(6J:581-90 (2001).

[572] Transformants of each DNA construct presented, in tissue culture, shoots with a patterned necrosis occurring in and immediately surrounding the vasculature of fully expanded leaf blades. It is thought that the necrosis resulted from a PCD signaling cascade.

[573] PCD has been the subject of considerable investigation by many researchers, and genes that are involved in PCD are claimed in multiple patent applications and patents, including U.S. Patent No. 6,451 ,604. [574] The transformants appear to initiate a PCD cascade specifically in the leaf blade vasculature and surrounding cells. These two genes are normally expressed in a xylem-preferred manner, as shown by the method of Example 11. It is thought that the putative polyphosphoinositide binding protein functions in the PCD signaling pathway that normally occurs during xylem development or leaf abscission. However, the transformants express the protein here ectopically. The ectopic activity appeared to be predominantly on older, fully expanded leaves. Ramets of most of the translines perpetuated this phenotype through propagation, suggesting that the phenotype observed is not a tissue-culture effect.

[575] To the forestry industry, modulation of the PCD signaling cascade has significant commercial importance. First, in some hardwood species, modulation of the PCD can be used to effect earlier PCD in developing xylem

through the use of tissue specific promoters. This, in turn, can result in smaller xylem cells, denser wood, and perhaps more compact overall habit. [576] Likewise, PCD can be down-regulated through the use of antisense or RNAi DNA constructs with tissue-specific promoters. It is thought that down- regulation of PCD in xylem can result in larger xylem cells and greater wood volume. Similarly, down-regulation of PCD in leaf tissue can result in delayed leaf abscission, thereby extending the duration of leaf photosynthesis and resulting in enhanced overall growth of the plant.

[577] Moreover, it is thought the phenotypic patterned necrosis occurs because the cell signaling gene products of pGrowthi and pGrowth2 require the presence of additional gene products to initiate or sustain the PCD signaling cascade. It may be the additional factors are present only in the vasculature of maturing leaves, i.e. not in leaf primordia or elsewhere in the leaf blade.

Example 22

[0578] Example 22 demonstrates the transformation of Eucalyptus grandis x Eucalyptus europhylla with the DNA constructs of Example 14 and the growth and propagation of transgenic E. grandis x E. europhylla plants.

[0579]pGrowth22 and pGrowth27 as described in Example 14, were used to transform clonal E. grandis x E. europhylla leaf explants. The leaf explants were transformed according to the protocol described in International patent publication WO00/12715, except where noted below. In brief, dissected leaf explants were inoculated with Agrobacterium comprising the DNA constructs pGrowth22 or pGrowth27. Inoculated explants were co- cultured for two weeks in diffuse light and selected on agar supplemented with 250 mg/L kanamycin and 250 mg/L timentin (omitting NAA from the transformation media). Leaf explants were then cultured for two weeks on on agar supplemented with 100 mg/L kanamycin and 250 mg/L timentin. The leaf explants were cultured for another two weeks on on agar supplemented with 150 mg/L kanamycin and 250 mg/L timentin. Thereafter and until healthy

single shoots were collected, the leaf explants were transferred monthly to fresh media containing 150 mg/L kanamycin and 250 mg/L timentin.

[0580] Single shoots were placed in elongation media in order to proliferate the putative transgenic tissue. The alongation media consists of Murashige and Skoog salts (MS) supplemented with imicroM 6- benzylaminopurine (BAP), 20 g/L sucrose and 7 g/L agar. PCR analysis of the explant tissue was conducted after approximately 200 mg of tissue is grown and collected. Both the promoter and gene sequences were verified using PuRe Taq Ready-To-Go™ PCR beads (Amersham Biosciences, Piscataway, NJ). PCR positive explants were then maintained as sock cultures through proliferation on elongation media supplemented with 150 mg/L kanamycin and 250 mg/L timentin.

[0581]Transgenic E. grandis x E. europhylla plants were propagated from these stock cultures. Where necessary, shoots were transferred monthly to fresh media. Single shoots were placed onto elongation media and maintained until reaching approximately 2-3 cm tall. Thereafter, single shots were placed into conventional rooting medium. After 10 days, the transformed plants were transferred to a green house with appropriate climate. A skilled artisan would recognize that many different culture media and intervals may be suited to regenerating plants of the instant invention. Using an appropriate humidity regime and fungicides to control fungal growth, plants were then grown in standard greenhouse conditions for 2.5 to 3 months before being moved to outdoor conditions for between 7 to 10 days for hardening.

Example 23

[0582] Example 23 demonstrated the effect of cell signaling genes on growth in the transformed plants of Example 22.

[0583] Eight ramets for each line transformed in Example 22 and an untransformed control were then planted in a field trial in a randomized block design. After 7 months of growth, plant height and diameter were measured to calculate the volume or biomass of the trees as described in Example 20. All

subsequent growth measurements are a comparison of the volume index calculated as described above.

[0584] Plants transformed with pGrowth22 or pGrowth27 resulted in significant volume growth increases compared to the control untransformed plants. Average volume growth increases of 47% and 161% respectively have been recorded.

[0585] Six out of 14 lines (43%) of pGrowth22 lines have volume growth gains of at least 50% compared to the untransformed controls. The top 3 lines have volume growth gains of 249%, 214%, and 107% or a mean increase of 190%. Eleven out of 15 lines (73%) of pGrowth27 lines have volume growth gains of at least 50% compared to the untransformed controls. The top 3 lines have volume growth gains of 455%, 337%, and 306% or a mean increase of 366%. Table 13 summarises the results for the putative cell signaling genes that were transformed into E. grandis x E. europhylla plants. Table 13: Exemplry growth data for cell signaling genes in E. grandis x E. europhylla transformants

[0586]

Example 24

[0587] Example 24 demonstrates the transformation of Pinus taeda with the DNA constructs of Example 14 and the growth and propagation of transgenic P. taeda plants

[0588]pGrowth1 , pGrowth2, pGrowth3, pGrowth11 , pGrowth21 , pGrowth23, pGrowth25 and pGrowth30 as described in Example 14, were used to transform clonal P. taeda. Specified clones of elite selected families of loblolly pine (Pinus taeda), was initiated as embryogenic cell lines from zygotic embryos of individual immature megagametophytes using the procedures described in U.S. Patent No. 5,856,191 , and maintained using the procedures described in U.S. Patent No. 5,506,136.

[0589]After one to three months of culture on maintenance medium, the tissue cultures were cryopreserved, stored for periods of up to several years, and retrieved using the methods of U.S. Patent 6,682,931. Those skilled in the art of plant tissue culture will recognize that other cryopreservation and recovery protocols would be applicable to the present method and that the detail in this example may not be construed to limit the application of the method.

[0590] Uniform suspension cultures from each of the genetically different tissue culture lines were established by inoculating a 250 ml Nephelo sidearm flask (Kontes Chemistry and Life Sciences Products) with 1 g of tissue each according to the method of U.S. Patent No. 5,491 ,090. The flasks containing the cells in liquid medium were placed on a gyratory shaker at 100 rpm in a dark culture room at a temperature of 23 0 C + 2°C. One week later, the liquid in each flask was brought to 35 ml by pouring 15 ml fresh medium into the culture flask and swirling to evenly distribute the cells. Cell growth was measured in the sidearm by decanting cells and medium into the sidearm portion of the flasks, allowing the cells to settle for 30 minutes and then measuring the settled cell volume (SCV). When the SCV was greater than or equal to half the maximal SCV (50% of the volume of the flask was occupied by plant cells), each culture was transferred to a 500 ml sidearm flask containing a total of 80 ml cells and medium and the transferred culture was maintained under the same conditions.

[0591] To prepare for gene transfer, polyester membrane supports were sterilized by autoclaving and placed in separate sterile Buchner funnels, and for each of six replicate plates per cell line, one to three milliliters of pine embryogenic suspension was pipetted onto each support such that the embryogenic tissue was evenly distributed. The liquid medium was suctioned from the tissues and each support bearing the embryogenic tissue was placed on gelled preparation medium for Agrobacterium inoculation according to the methods described in U.S. Patent Publication No. 20020100083. Specifically, the constructs pGrowthi , pGrowth2, pGrowth3, pGrowth11 , pGrowth21 ,

pGrowth23, pGrowth25 and pGrowth30 as described in Example 14, were each introduced into different isolates Agrobacterium tumefaciens by techniques well known to those skilled in the art, and virulence was induced with administration of acetosyringone by commonly used techniques whereupon each of the induced Agrobacterium isolates was co-mingled with separate replicates of the plant material according to the methods described in U.S. Patent Publication No. 20020100083. The cells were co-cultivated in the dark at 22° + 2°C for approximately 72 hours.

[0592] Following co-cultivation, Agrobacterium was eradicated from the cultures according to the methods described in U.S. Patent Publication No. 20020100083. Cells borne on polyester membrane supports were then transferred onto fresh selection media at intervals of 2 weeks. Active growth on the selection medium occurred in a number of isolated sectors on many of the petri dishes. Such active growth in the presence of selection agent was normally an indication that the growing tissues have integrated the selection gene into their chromosomes and are stably transformed. These areas of active growth are treated as independent transformation events and were henceforth referred to as putative transgenic sublines. The putatively transgenic embryogenic tissue was multiplied by transferring growing transgenic sectors to fresh semi-solid maintenance medium supplemented with the respective selection agent.

[0593] Putatively transformed sublines, after reaching approximately 2g, were chosen for polymerase chain reaction (PCR) amplification for verification of the presence of transgenes using standard techniques. Lines that had been verified by PCR were selected for testing alongside lines transformed with the GUS control construct pWVR31.

[0594]Germinable embryos were produced from each of the selected lines verified as transformed by PCR, as follows. After the cell masses cultured on selection medium have proliferated to at least one gram, each culture was separately resuspended in liquid medium. When the cell suspensions were brought to uniform (half-maximal) SCV, equivalent amounts

of suspension culture cells were pipetted onto sterile membrane supports for placement on development/maturation medium as described in U.S. Patent No. 5,506,136 to develop high quality harvestable stage 3 (cotyledonary) embryos. Dishes were incubated in a dark growth chamber at 23 + 2°C. The membrane supports were transferred to new petri dishes containing fresh medium every 3 weeks. At week 9, stage 3 (cotyledonary) embryos were visually analyzed for germination quality and harvested onto fabric supports on medium as described in U.S. Patent No. 5,506,136, and incubated for about four weeks in the dark at a temperature of 4°C±2°C. Next, embryos on their fabric supports were incubated above water in sealed containers for about three weeks in the dark at a temperature of 25°C±2°C. Following the above two treatments, embryos on their fabric supports were transferred to medium germination medium and incubated for about three days in the dark at a temperature of 25°C±2°C. Embryos were then removed from their fabric supports and placed onto the surface of fresh germination medium. Germination was conducted in the light at a temperature of 25°C±2°C. Germination plates were examined weekly, over a period of about four weeks, and germinating embryos were transferred to MAGENTA® boxes containing 100 ml of germination medium for conversion to plantlets. MAGENTA® boxes containing developing plantlets were incubated in the light at 25°C+2°C for about eight to twelve weeks.

[0595] When the plantlets formed epicotyls (newly formed shoots of approximately two to four cm), they were transferred to containers filled with a potting mix [2:1:2 peat:perlite:vermiculite, containing 602 g/m 3 OSMOCOTE fertilizer (18-6-12), 340 g/m 3 dolomitic lime and 78 g/m 3 MICRO-MAX micronutrient mixture (Sierra Chemical Co.)]. The plantlets were grown in a shaded greenhouse and misted infrequently for a period of about two weeks. They were removed from mist for acclimatization in the greenhouse for 5 to 6 months. Plantlets were then transferred to outdoor conditions for 7 to 10 days final acclimatization before field planting.

[0596] Once transformed and propagated, a skilled artisan would also recognize the accelerated reproduction of Pinus plants can occur by grafting of the plantlets. See, e.g., Mergen, F. (1954) Rooting and grafting of slash pine (Pinus elliottii Engel.) for application in forest genetics. Ph.D. dissertation, Yale University, New Haven, CT; and Ahlgren, CE. (1967) A relationship between scion, bud origin and growth of white pine grafts. Minnesota Forestry Notes 180. University of Minnesota, St. Paul. 2 p.

Example 25

[0597] Example 25 demonstrated the effect of cell signaling genes on growth in the transformed plants of Example 24.

[0598] Four ramets for each line transformed in Example 24 and the GUS control (pVWR31) plants were then planted in a field trial in a randomized block design. After 15 months of growth, plant height and diameter were measured to calculate the volume or biomass of the trees. Height was measured between the root collar and the terminal bud, while diameter was measured at the root collar. The volume index was calculated by multiplying the square of the root collar diameter by the height. All subsequent growth measurements are a comparison of the volume index calculated as described above.

[0599] After 15 months of growth, plants transformed with pGrowthi , pGrowth3, pGrowth11 , pGrowth21 , and pGrowth30 had growth increases of 34%, 8%, 28%, 10%, and 28% respectively when compared to the mean growth of the GUS controls. Two out of 8 lines (25%) of construct pGrowthi had growth increases exceeding 50%; growth increases of these two lines were 103% and 70%. One out of 10 lines (10%) of construct pGrowth3 had growth increases exceeding 50%; the growth increase of this line was 136%. Two out of 8 lines (25%) of construct pGrowth11 had growth increases exceeding 50%; growth increases of these two lines were 106% and 81%. One out of 8 lines (13%) of construct pGrowth21 had growth increases exceeding 50%; the growth increase of this line was 109%. Two out of 9 lines (22%) of construct pGrowth30 had growth increases exceeding 50%; the

growth increases of these two lines were 116% and 71 %. Table 14 summarises the results for the putative cell signaling genes that were transformed into P. taeda plants.

Table 14: Exemplry growth data for cell signaling genes in P. taeda transformants

[060O]A summary of results in examples 16, 17, 18, 20, 21 , 23, and 25 are presented in table 15.

* * * * *

[601] While the invention is described with reference to exemplary embodiments, it will be understood by those skilled in the art that various changes may be made and equivalents may be substituted for elements thereof without departing from the scope of the invention. In addition, many modifications may be made to adapt a particular situation or material to the teachings of the invention without departing from the essential scope thereof. Therefore, it is intended that the invention not be limited to the particular embodiment disclosed as the best mode contemplated for carrying out this invention. All references and publications cited herein are incorporated by reference in their entireties.

TABLE 1: Cell signaling genes and corresponding gene products (continued)

TABLE 1 Cell Signaling Genes and Corresponding Gene Products

TABLE 1 : Cell signaling genes and corresponding gene products (continued)

TABLE 1: Cell signaling genes and corresponding gene products (continued)

TABLE 1: Cell signaling genes and corresponding gene products (continued)

TABLE 1: Cell signaling genes and corresponding gene products (continued)

TABLE 1: Cell signaling genes and corresponding gene products (continued)

TABLE 1: Cell signaling genes and corresponding gene products (continued)

TABLE 1: Cell signaling genes and corresponding gene products (continued)

TABLE 1: Cell signaling genes and corresponding gene products (continued)

TABLE 2 Cell Signaling Gene Sequences

SEQ ID NO Sequence

1 GCAAGCTAAGCTAAGGGAGCGGTTACCCTCGCGAAAGCAAGAACCTTTCAGTTCACGCAG A

AGAGAGAGAAAGAAAGAGAGAGATGGAGAGGGAGAGAGAGCAGCAGGTTTACCAGGC GAG

GCTCGCGGAGCAAGCCGAGCGATACGATGAGATGGTTGAGTCGATGAAGCAAGTAGC TAA

GCTGGATGTGGAACTGACTGTTGAGGAGAGAAATGTGTTGTCTGTTGGGTATAAGAA TGTG

ATTGGGGCCAGAAGGGCATCATGGCGGATTTTATCTTCCATTGAGCAGAAGGAGGGG ACCA

AGGGTAACGAGCAGAATGTGAAGAGGATCAAGGACTACAGGCAAAGGGTTGAAGATG AGCT

CGCCAAGATCTGCAGTGACATACTCTCAGTCATTGATAAGCATCTTATCCCATCCTC CTCAA

GTGGAGAGTCGACTGTTTTCTACTATAAGATGAAAGGTGATTATTGTCGTTACCTTG CTGAAT

TCAAGGCTGGTGATGACCGCAAAGAAGCTGCTGATCAGTCGCTCAAGGCATATGAGG CTGC

CAGTTCCACTGCTTCAACGGATTTGGCTCCAACTCACCCTATCAGACTTGGACTGGC TTTGA

ATTTCTCCGTCTTCTATTATGAAATCATGAACTCGCCAGAAAGGGCATGCCATCTGG CTAAA

CAAGCTTTTGATGAGGCTATCGCGGAACTCGATAGCCTAAATGAAGACTCCTATAAG GACAG

TACCCTCATTATGCAACTTCTTAGGGACAATCTTACACTATGGACTACAGATCTGCC TGAAGA

AGGAGGTGAGCAATCCAAAGTTGATGAGCCTGCGGCAGAGAGTTAATTGGGCAAAGT AGAC

GCTTCCTGATGATTTCAATTCTTTGGGGGACATTGAGGCTTGCTAGGGCAGGAGTCA TGGT

CTTATGCGATGGTGCAGTTAGTAGACTGTTGGTCTGTATTTACTTATTTAACAGAAT GCTTCT

CCACAGTGTTGTGTTTGTGCTGGTTACACGATTGAATACTGTTATCTTTGTCCTATA AAACAC

GGAAGCCTTTTCTCAAAAAAAAAA

GGAGAAGCGCCTTTTTTTTCCTTTCTCTCTCCCTTGCTTTCGTTTCTCCATTTGTGG TTTTTCC

GTTTTTTCCACGTCGCTCCCAGCGGATACGCGTCTTCCGCCACCTCATCTCGCCCCG CCGT

ATAAATTCGGAGTCCTCCCTGGCGCACTCCCCTCTCGCGTCCGTCCGCAAAACACTC CCCC

CGCCCGCAGCTCGCTCCGCCCGGCTTTTTCTCGCTCGCTCGCTCGCGATTCTTGCTC TTCC

GCAAATCCCTAGTCGAGAGTTAGGTTTCGTAACAGTACACGGAAGATGTCGCCCTCT GATTC

TTCACGGGAGGAATATGTGTACATGGCCAAGTTAGCTGAACAGGCTGAGCGGTACGA GGAG

ATGGTGGATTTCATGGAGAAAGTTGCCAAGACTGTAGACGTCGAGGAGCTAACCGTT GAGG

AACGTAACCTTTTGTCTGTGGCGTACAAGAATGTGATTGGGGCCAGGAGGGCATCGT GGAG

GATCATTTCTTCCATTGAGCAGAAGGAAGAGAGCAGGGGTAACACTGATCATGTCTC GATCA

TTAAGGACTACAGGGGAAAGATCGAGTCCGAGCTCAGCAAGATCTGTGAAGGCATTC TCAG

CCTTCTTGAGTCGCATCTCATTCCTTCAGCCTCCTCTGCTGAGTCCAAGGTGTTTTA CCTTAA

GATGAAAGGTGATTACCACAGGTATCTGGCAGAGTTTAAGACTGCGACTGAAAGGAA AGAA

GCTGCCGAGAGCACTTTATTGGCCTACAAATCTGCTCAGGATATTGCTGGGGCCGAA CTGG

CTTCTACTCACCCAATTAGGCTGGGACTTGCGCTGAACTTCTCTGTTTTCTACTATG AAATAC

TTAACTCTCCTGATCGGGCTTGCGCTCTTGCAAAGCAGGCATTTGATGAGGCCATCG CTGA

GTTGGATACGCTGGGCGAGGAATCATACAAGGACAGTACATTGATCATGCAACTTCT TCGA

GATAACTTGACTCTGTGGACTTCTGATCTCACGGATGAAGCTGGGGATGACATTAAG GAAG

CTTCGAAACTGGAGTCTGGAGAGGGGCAGCAATGATTTGCTAGGATGATGTCAGTAC TTTAA

TGATATTTTGCACCGTCGTAGATGCCTTGTGGTTTGTCACAGTGAAGATTATTTATG AACTGA

GAGTGCTATAAGTTGTTTCTCTAGTGTTCCTTGAAAAAAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

CAAAAGCAATCTACATTTCTTTCTTTGATTACCAGGACAAATAAAATAAGATGCTAT ACCAGA

GCAGTATCAGTGTTACACAAGAATCAAATAGGATTTGGCACCTCAAAGGCAGATAAA TTGAT

TAAATGGCCACAAATTGGAAAGCATCATTCAAAAGATAAGTCACAAGAGCTCCTCAA ACCTG

AACAATAAATTATATTCACCATGACCACAGCAATGAGCATCACATGATTGAGAATCT CGTTGC

ACAAGCCCACAAGACAGGTGAACTATCAATCTGACTTTCTTGGCCATCCAAAGCAGT GATTC

CTCATTGTAAAAATTTAATCAATCTTTTGCTATTAGGCAATTCTTCCATAGTCTTTT CTTCCAC

GAGTTGTTGGAGGTATGTTTGTGAAAGCATCACTGGCCCTTCGCCCCCACTCTCGCT CACC

TCCGAACGAGAGAGTCCCAATCATTCGCAGCTTCGCAGCTTTTGTAATTTGATCAGC ACGTT

GAAGATGGCGGCAGCTGATTCTTCACGCGAGGAAAATGTGTACATGGCCAAGTTGGC TGAA

CAGGCCGAGCGTTATGAGGAAATGGTGGAATTTATGGAGAAAGTGGCCAAGACGGTT GATG

TCGAGGAGCTTACTGTTGAGGAACGTAACCTCCTCTCCGTGGCATACAAGAATGTGA TTGGT

GCCAGGAGGGCTTCATGGAGGATCATCTCTTCCATTGAGCAGAAGGAAGAGAGCAGG GGA

AATGAGGACCATGTTGTGATTATCAAGGAGTATAGGGGGAAGATTGAGACTGAGCTC AGCA

AGATCTGTGATGGCATCCTCAATCTCCTTGAGTCGCATCTCGTTCCATCAGCCTCAT CTGCT

GAGTCAAAGGTGTTCTATCTGAAGATGAAGGGTGATTACCACAGGTACTTGGCTGAG TTTAA

GGCGGGAACTGAGAGGAAAGAGGCTGCTGAGAGCACCTTGTTGGCTTATAAATCTGC TCAG

GATATTGCTTTGGCTGAGCTGGCTCCCACTCACCCTATTAGGCTTGGACTTGCTCTT AACTT

CTCTGTGTTCTATTATGAAATTCTCAACTCACCTGATCGTGCCTGCAGTCTGGCTAA ACAGG

CATTTGATGAGGCTATCTCCGAGCTAGATACATTGGGTGAGGAATCATACAAGGACA GCACA

TTGATTATGCAACTTCTCCGAGATAACCTAACACTCTGGACTTCCGATGTCACGGAT GAAGC

TGGAGATGAGATCAAGGAATCTTCAAAAAGGGAGTCTGGTGAGGGGCAGCCACCACA GTGA

CGAGCTCCATTCGAAGATGGCTTCTCTGTACTTTAAGACTGTGAACTCTTATGTAGG CAGCG

CTTTGTTATAACATCATTTGGTCAGCACCATGATCTTAGTACTTGCACTGCTTTTGG GTGAAA

GTATTATGGGACTGTGTACTTTTCTCTGGTTAGTTATGGGAAGAGATTGACTTGATG CAGTG

CTCTGTTTTGTCTCGTGGTAGTGATGTCAGTGGTTTTCTTATTGTGAAGTGAATAAT TCTATA

GACTCACACTACCAATGGTTCACAAAGTGATTGTGGTAGACATATGTCGAGTGCTTT AATTG

GTTCGCCGTTTCATGTCAAATGCTATCACCTTTTGCCAAAAAAAAAA

GCGTCGTCCTCCTTCCTCCTCCCCCTTCCTCACCAGCCAGTCGTCGTCTGCTTGAGG GCTA

GAGAGAGAGAGAGAGTAGAGAGAGAGTAGAGAGAGAGTGTAGAGAGAGAGAGAGAGA GAG

AAGGAGATGGCGTCGACGAAGGAGAGAGACGGCTACGTCTACGTCGCCAAGCTCGCC GAG

CAGGCCGAGCGCTACGACGAAATGGTGGAGGCCATGAAGAATGTGGCGAAGCTCGAT GTG

GAGCTGACGGTGGAAGAGAGGAACCTGCTCTCCGTCGGTTACAAGAACGTGATCGGC GCG

CGGCGGGCGTCGTGGAGGATCCTCTCTTCCATCGAGCAGAAGGAGGACTCGAAAGGG AAC

GAGCATAATGTGAAGAAGATCAAGGAGTTCAGGCAGAAGGTCGAGGCCGAGCTGGCG AAT

ATCTGCGGGGATGTGATGAAGGTGATCGATGAGCATTTGATTCCTTCGTGTGCTGGT GGAG

AATCGACCGTGTTTTTCTATAAAATGAAAGGAGATTACTATCGGTACTTGGCAGAGT TTAAGG

CTGGTGATGACAGAAAGGAGGCAGCTGATCAGTCTATGAAAGCATATGAGCTGGCTT CCAC

CACCGCAGAGGCTGACCTATCCCCGACACATCCAATCAGATTGGGTTTGGCATTGAA CTTTT

CTGTCTTCTACTATGAGATCATGAACTCTCCTGAAAGGGCCTGTCACCTTGCAAAGC AGGCT

TTTGACGAAGCGATCTCAGAGTTGGATACTTTGAGTGAGGAATCCTACAAAGACAGC ACATT

AATTATGCAGCTTCTAAGGGACAATCTGACATTATGGACTTCTGACATCCCTGAGGA TGGAG

CTGAAGATGCTCAGAAGCTTGACAATGCTGCCAAAGCTGCAGGAGGTGAAGATGCAG AGTG

AGGCAGAGTGTTGCTTGGGAGCTCATAAAGGGAGTCAAATGGTTTGAGGGTGGTGTT TCCT

TGTCTGAAGGCATATTGAGAGACTTTTACTTTCTGTTTCCTTCACTTTTTTCGTTTC GTCGTCC

TCTTTTGCTTCGACATTGCTACTAGCTAATTATTTGGTGCTTGTTCTGTGCTCCCAT TCTCAC

GTCTGCTGATTAAACCTGATAAAAATTATGTCAAGACAGTCTGTTGTACGATCTAAG TCTGTT

TAATTGAGAATGTAGCGTTATTAGATGATGAATCTCAACAGTTGTGCAATCGGATGT TAAGG

CCTACTTGTTAATCTAAAAAAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

AAGAGATGGCAGAGCACCGCAGCTATGGAAATGTGAATCTAAAGACGTTTGATGCTC ATGTT

CCGGAGATTAAGTTCACCAAGCTCTTCATCGACGGCGAGTTCGTCGATTCTGTCAAA GGAA

GGACATTCGAGACGAAAGATCCAAGAAATGGACAAGTGGTGGCAAGAGTCGCGGAGG GAG

ACGAAGAGGACGTGGAGTTGGCCGTGATTGCTGCCCGTCGAGCATTTGATCACGGCC CTT

GGCCACGCATGCCCGGCTATCAAAGGGGAAGGATCATGTCAAAATTTGCAGACTTGA TCGA

AGAGAACATAGACGAACTAGCTGCTCTGGACACTATAGATGCCGGGAAGCTATTCAG TGTC

GGCAAGGCCCGGGACATTCCTAACGCTGCCATGCTGCTGAGGTACTATGCCGGTGCG GTG

GATAAGATCCACGGCGAGGTATTGAAGATGTCGCGCGAGCTTCACGGGTACACGCTA CGG

GAGCCGGTTGGCGTGATCGGGCACATCATCCCTTGGAACTTCCCGACCGGGGTGTTC TTCA

TGAAGGTCGCCCCAACACTGGCGGCTGGTTGCACCATGATCGTGAAGCCCGCCGAGC AAA

CCCCTCTATCGGCTCTCTTTTACGCTCATTTGGCTAAGAAGGCTGGTGTTCCTGATG GAGTG

ATCAATGTCGTTACCGGTTTTGGACCGACAGCTGGTGCAGCGATAAGTAGTCATATG GACAT

TGATATGGTTAGTTTTACGGGGTCTACAAAAGTAGGACACATGGTGATGCAGGCCGC GGCA

ACGAGCAATTTGAAACAAGTGTCGCTTGAATTGGGGGGCAAATCACCTCTTATAGTC TTTGA

TGATGTCGATTTAGATACCGCTACTAATCTTGCTCTGACTGGTATCCTCTATAACAA GGGAG

AAGTATGCGTCGCAGGATCTCGTGTCTATGTTCAAGAAGCGATCTATGAAGAATTCG AGAAG

AAGCTAGTGGCAAAGGCCAAGGCTTGGCCGGTCGGTGACCCATTTGATCCGAATGTC CGTC

AAGGACCGCAGGTCGATAAGAAACAGTTTGAGAAAATACTTTCTTACATCGAGCATG GAAAG

AGAGAAGGAGCTACACTTTTGATTGGGGGTGAGCGTCTAGGCACCGAAGGGTACTAC ATTC

AGCCAACAATCTTCACAGATGTTAATGAGGACAATGTGATCGTAAAGGATGAGATTT TCGGC

CCCGTCATGTCACTCATGAAATTCAAGACCATGGAGGAGGTGATCAAGAGGGCCAAT GACA

CGAGGTACGGTCTAGCGGCGGGAATTCTGACAAAGAACATAGATCTAGCAAACACGG TCTC

AAGGTCAATCCGAGCAGGTATGATTTGGATAAATTGCTACCTTGCAGTTGACAACGA CTGTC

CTTATGGTGGCTACAAGATGAGTGGCTTTGGCAAAGATCTTGGCTTGGACGCTCTCC ACAAA

TACCTACATGTCAAATCTATCGTGACCCCCATTTATAACTCTCCCTGGCTTTGAGAG AGTTTT

TTTTTTCTTAGTGGGCGCTGGATTGCATCATCAGACGGGTCAAATAATATATAATTA GAAGTG

TATTTGTTTGAGTGAAAATATTTTTCCCGAAAAAAAAAA

IABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

AGGAGAGAGACGAGATGGCAGAGAACCAGAGCGACGCCAACGGGAGCCTGAAGACTT ATG

ATGAACACGTTCCGGACATCAAGTTTACCAAGCTCTTCATCAATGGCGAGTTCGTCG ATTCT

GTCAAAGGGAGGACGTTCGAGACGATAGATCCAAGAAATGGAGAAGTTACAGCAAGA GTTG

CAGAGGGAGACAAAGAGGACGTGGATTTGGCTGTGAAAGCCGCCCGTCAAGCATTTG ATCA

CGGCCCTTGGCCACGCATGCCCGGCTACCAAAGGGGAAGGATCATGTCGAAATTTGC GGA

CTTGATCGAAGAGAACATAGATGAACTGGCTGCTCTGGACACTATCGACGCCGGGAA GATA

TTCAGCATGGGCAAGGCCGTGGACATCCCTCACGCTGCCACATGTCTAAGGTATTAT GCCG

GCGCAGCGGACAAGATCCATGGTGAGGTGTTGAAGATGTCGCGTGAACTTCATGGGT ACAC

GCTGCTGGAGCCGGTTGGCGTGGTCGGGCACATTATCCCTTGGAACTTCCCGACCAG CAT

GTTCTTTATGAAGGTCGCCCCAGCACTGGCGGCTGGTTGCACCATGATCGTGAAGCC TGCC

GAGCAGACCCCTCTGTCGGCTCTCTATTATGCTCATTTGGCTAAGAAGGCCGGTGTT CCTAA

TGGAGTGATCAATGTTGTAACTGGTTTCGGACCAACGGCCGGTGCTGCAATAACCAG TCAT

ATGGACATTGATATGGTCAATTTTACGGGGTCTACAAAAGTGGGGCGCATCGTGATG CAGA

CTGCAGCGACAAGCAATTTGAAACAAGTGTCACTCGAATTAGGCGGGAAATCGCCTA TTATG

ATATTTGATGATGCTGATTTAGATACTGCTACCGATCTTGCTCTAATAGGTATCGTC CATAAC

AAGGGAGAAATATGCGTCGCGGGCTCTCGCGTTTATGTTCAGGAAGGGATCTATGAA GAGT

TTGAGAAGAAGCTGGTGGCAAAGGCAAAGGCTTGGCCAGTCGGTGACCCATTTGATC CGAA

AGTCCAACAAGGACCGCAGGTCGATAAGAAACAATTTGAGAAGATACTTTCTTATAT CGAGC

ATGGAAAGAGAGAAGGGGCCACGCTTTTGACTGGGGGCGAGCGTTTGGGCACCAAAG GGT

ACTATGTTCAGCCAACAATTTTCACAAATGTTAAGGAGGACAATGTGATCGTGAAGG ATGAG

ATTTTTGGTCCTGTCATGTCGCTCATGAAATTCAAGACTGTGGAGGAGGCGATCAAG AGGG

CTAACGATACTAGGTATGGTCTAGCAGCAGGGATTGTGACGAAGAATATAGATGTGG CGAA

CACAGTCTCGAGGTCAATTCGAGCGGGTGTCATATGGATAAACTGCTACTTTGCATT CGACA

ATGACTGTCCTTGTGGTGGTTACAAGACAAGCGGCTTCGGGAGAGATCTCGGTTTGG ATGC

CCTCCACAAATGCCTACATGTTAAATCTATTGTGACCCCGCTTTATAACTCTCCATG GCTTTA

AGAGAATTTTCTAGGAAAAGAGCTTTGAGTCATATGGTGGCTCAAATAATGTGTAAT TCCAAA

TTATGAGGT ATATTTGCAATAAACAAAATGCAGGTCATTTTGGCAAAAAAAAAAAAAAAAAAA

AGCAAGTGTCAAAGCCATTCTAGTCCACTTGCCTTGGTGGAATGGGTTTGTTGTGTA TTCTT

AAATGATCTGCCCTACTCTCTGCTCCTTTGTCGTCTTTTATATATTTTTGATATTGG TAATGAG

GAGATGAATTCTTCTGTGTCCTTTGTATGTCTTATAGTCTGATATCATCATGAGTGA TGAAGT

TGGTCGAAGAGCATATTGTGCAAACTGCTAAACTTGAGTTGTACTATGGGGGGTTTA CAGTT

TAAAAAAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

GGATTTTGAGTGCAGAGATGAGAGAGAGGGAGATGGCAGAGAACCAGAGCAATGCCA ACG

GGAGCCTGAAGACTTATGATGCTCATGTTCCAGAGATTAAATTCACCAAGCTCTTCA TCAAT

GGCAAGTTCGTCGATTCTGTCAAAGGGAGGACATTGGAGACGATAGATCCAAGAAAT GGAC

AAGCGACGGCGAGAGTTGCCGAGGGAGACAAAGAGGACGTGGATTTGGCTGTCAAAG CTG

CCCGCCAAGCATTTGATCACGGCCCCTGGCCGCGCATGCCCGGCTATCAAAGGGGAA GGA

TCATGTCGAAATTTGCGGACTTAATCGAAGAGAACATAGACGAACTAGCTGCTCTGG ACACT

ATAGATGCCGGGAAGCTATTTAGTGTCGGCAAGGCCCAGGACATCCCTCACGCTGCC ACGA

TGCTGAGGTACTATGCGGGTGCAGCGGATAAGATCCACGGCGAGGTATTGAAGATGT CGC

GCGAGCTTCACGGGTACACGCTACGGGAGCCGGTTGGCGTGATCGCGCACATCATCC CTT

GGAACTTCCCGACCGCGGTGTTCTTTATGAAGGTCGCCCCAGCGCTGGCGGCTGGTT GCA

CCATGATCGTGAAGCCCGCCGAGCAAACCCCTCTATCGGCTCTCTTTTACGCTCACT TGGC

TAAGAAGGCCGGTATTCCTGATGGAGTAATCAACATTGTAACTGGTTTTGGACGGAC AGCC

GGTGCGGCGATAAGCAATCACATGGACATTGACATGGTTAGTTTTACGGGGTCTACA GAAG

TGGGACGCATTGTAATGCAGGCCGCAGCAACAAGCAATTTAAAACAAGTGTCGCTCG AATT

GGGCGGGAAATCACCTCTTATAATTTTTGATGATGTTGATTTAGATACTGCTACTGA TCTTGC

TCTAACCGGTATCCTCCATAACAAGGGAGAAATATGTGTTGCGGGCTCTCGTGTCTA TGTTC

AAGAAGGGATCTATGAAGAGTTCAAGAACAAGCTAGTGGCAAAGGCAAAGGCTTGGC CGGT

CGGCGACCCATTTGATCCGAATGTCCGTCACGGACCGCAAGTCGATAAGAAACAGTT TGAG

AAGATACTTGCATACATCGAGCATGGAAAGAGAGAAGGAGCCACGCTTTTGACTGGG GGCG

AGCGTCTGGGCACCGAAGGTTACTACATTCAGCCAACAATCTTCACAAATGTTAAGG AGGAC

AACATGATTGTGAAGGATGAGATTTTCGGCCCTATCATGTCGCTCATGAAATTCAAG ACCAC

GGAGGAGGTGATCAAGAGGGCCAATGACACGAGGTATGGTCTAGCAGCAGGGGTTTT GAC

GAAGAACATAGATATGGCGAACACAGTCTCGAGGTCAATTCGAGCAGGCACCATCTG GATA

AATTGCTACTTTGCATTCGACAATGACTGTCCTCTTGGCGGCTACAAGATGAGCGGC TTTGG

CAGAGATTTTGGTTTGGACGCTCTCCACAAATACCTACAAGTCAAATCTGTTGTGAC CCCCA

TTTACAAGTCTCCCTGGCTTTGAGAGAAATTTAGGCAAGAAGGGGGATGGGGGGCAT TTGC

ATCATCTGATGGCTCAAATTATCAAATTATGAATGATTAAGAGTGTATTTGTTTGGC TGAAAG

CATTTTCACTCGTGTAATTTGCTGAAAATGATCAATAAATGAGAATCATTTATGGCC AAAAAA

AAAA

AAAATTTCGGAAGATCCCCAATCCGTTTCAAATTCTCTCGATCAAGGACCCCACGTT TTTCCT

CCAAATCCAAAACCCTAATTCTCCGCATCTCGATCCGTCGCAGATCTCTCCTCGCCG CCCTC

CTCCCCGCCCTCCTCCCCATGGCATCTCGCAGGCGCATGCTGCTCAAGGTCATCATC CTCG

GCGACAGCGGGGTCGGGAAGACGTCTCTCATGAACCAGTACGTCAACCGCAAGTTCA GTAA

CCAGTACAAGGCGACCATTGGAGCTGATTTCTTGACGAAGGAAGTTCAGTTTGAAGA TCGAT

TGTTCACATTGCAGATATGGGATACTGCTGGGCAAGAAAGGTTCCAGAGTCTGGGTG TGGC

TTTTTACCGAGGTGCAGACTGCTGCGTCCTTGTTTATGATGTGAATGTCATGAAATC ATTTGA

TAATCTTAACAACTGGAGGGAAGAGTTTCTACTTCAGGCCAGCCCATCAGACCCTGA AAACT

TTCCATTCGTCGTGTTGGGGAACAAGATAGATGTTGATGGTGGTAATAGTCGTGTGG TTTCT

GAAAAGAAAGCAAAGGCTTGGTGTGCTTCTAAGGGAAACATCCCTTATTTCGAGACA TCTGC

AAAAGAAGGATTCAACGTGGAGGCTGCATTTGAGTGTATAGCTAAAAATGCTTTGAA GAATG

AACCTGAAGAAGAAATATACCTTCCCGACACCATTGACGTCACTGGTGGAGGACGGC AGCA

GAGATCTACTGGCTGTGAATGTTGAAGAGAATTAATTGGCTACTCTTTCCTGGGAAT GGAAA

TACAGTGGAACCGATTTATCGTGATTCATTGCTCAATAACTATTACGTAAGAGACTA ATGTAG

GCGACCAGATCAAACTCTCATCATGTATCATTAGTAGATCAAGGAAGACTGTTCCTT GGTCT

TATCGGTTCCCTCTTCTAATGTTAGTAGTTTACAAGTATAATTTGTTTGGACATGTA TTCTTGG

GTATGAGTTTGCTTTGAAGTAAAAAAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

TCTCTCTCTCTTCAAATCAATCCACCCCCAAATCCTCCTCCTCCTCCTCCGCCCCTC GCTTTC

TCTCTCTAGATCGATCGGCCGGTCGATTTGATCGGAGCAGCTGCGGCGAGTCGGAGC GGG

GCGATGGCGGTGCCGGAGAACCTGGGCAGGGACCAGTACGTGTACCTGGCGAAGCTG GC

CGAGCAGGCGGAGCGGTACGAGGAGATGGTGGAGTTCATGCACAAGCTGGTCGTCGG CTG

GACGCCGGCCGCCGAGCTCACCGTCGAGGAGCGGAACCTCCTCTCCGTGGCCTACAA GAA

CGTGATCGGCTCGCTCCGGGCGGCCTGGCGCATCGTCTCCTCCATCGAGCAGAAGGA GGA

GGGCCGGAAGAACGAGGACCACGTCGTCCTCGTCAAGGAGTACAGATCCAAGGTCGA GAA

CGAGCTCTCCGACGTGTGCGCCAGCATCCTCCGCCTCCTCGACACGAATCTGGTCCC CTC

GGCCGCCGCCAGCGAGTCCAAGGTGTTCTACCTGAAGATGAAGGGGGATTACCACCG GTA

CCTGGCCGAGTTCAAGGTCGGCGACGAGAGGAAGGCCGCCGCCGAGGATACCATGCT CG

CTTACAAGGCGGCTCAGGATATCGCTCAAGCAGATCTGGCTTCAACCCATCCAATAA GGCT

GGGTCTGGCACTCAACTTCTCTGTGTTCTATTATGAGATCCTTAATCAGTCTGATAA AGCTTG

CAGCATGGCCAAACAGGCATTTGAGGAAGCAATTGCTGAGCTGGATACATTGGGTGA AGAA

TCATACAAGGACAGCACTCTCATCATGCAGCTGCTAAGGGATAATTTCACCCTCTGG ACTTC

TGATGTGCAGGACCAATTGGATGAGCCCTAGAAGATGCAGCGTAAGCTCAACGGAAA TTCG

AAACTTTGTTCTGGGAGGAGGTGGGCTGTGAAATGTCATTTGTCGGTACCGATTTAA AGCGT

GCATCAGTGACATGTTTCTCTTTTATTTTTAGATTATTAAATCCTTTTCCTGTTTCC AAAACGA

ATTGGAAAACGCTCTTGGGTTTGTGAACGTGCTTCTCACTGCTTTAGTGTTGGTTTT CACTG

GATAAAAAAAAAA

10 CTCTCTCTCTCTCTCCGCCAAACGCTCTCGAAGAAATCACCAGGGAAAAAAAAAAAAGAA AA

AAAAGAGAAAGAAAAAAGATCAGGAAATCGAAAAAACCGAAAGAGGAAGAAGAGAAC CCCC

CAAATCCCCCCCTCCCCCAGTTCCAGATCTAGAAGCCCCGGCGAGCAGCGAGCGAGC AGC

AATGGCGACGGCACCATCGGCGCGCGAGGAGAACGTGTACATGGCGAAGCTGGCGGA GC

AGGCGGAGCGCTACGAGGAGATGGTGGAGTTCATGGAGAAGGTCGCCGCCGCCGCCG CC

GCCGCCGACGCCGAGGAGCTCACCATCGAGGAGCGCAACCTCCTCTCCGTCGCCTAC AAG

AACGTCATCGGCGCCCGCCGCGCCTCCTGGCGCATCATCTCCTCCATCGAGCAGAAG GAG

GAGAGCCGCGGCAACGAGGACCACGTCGCCGCCATCCGCGACTACCGCTCCAAGATC GAG

TCCGAGCTCTCCGGCATCTGCGCCGGCATCCTCAAGCTCCTCGACTCCCGCCTCATC CCCG

CCGCCGCCTCCGGCGACTCCAAGGTCTTCTACCTCAAGATGAAGGGCGACTACCACC GGT

ACCTCGCCGAGTTCAAGACCGGCGCCGAGCGCAAGGAGGCCGCCGAGAGCACCCTCA CC

GCCTACAAGGCCGCTCAGGACATTGCCAACACGGAGCTTGCTCCGACTCACCCAATC CGG

CTCGGACTAGCCCTCAACTTTTCTGTTTTCTACTATGAGATTCTGAATTCTCCTGAC CGTGCT

TGCAGTTTGGCCAAGCAGGCTTTTGATGAAGCAATTGCTGAGTTGGATACACTTGGA GAGG

AGTCTTACAAAGACAGCACTTTGATTATGCAACTTCTTCGCGACAACCTCACCTTGT GGACTT

CCGACATGCAGGAAGACGGTGCAGACGAGATTAAAGAAGCACCGAAGGCTGATGAAC AGC

AGTGAGGTCTTGACTATTGCTCGCTGTCAAATTTCTCCATTCAATGTTTTTACTTGG AGAAGG

TGCTTGTTGCTGATTTCTCTTTTATTCCGAAGTTGGAGGCATCATCGTCTCTTTTTA TTTGTTT

CTGACTTTAGTTTGTCTCATCAATCTCCTCATGTGCTATCAATTGTGCCTTATTTTT CTTGGAG

GCATGGAGCTTCAAATTCTGCATTGAGTGTAGCAGATCCCTTCTATTAGATTATTCA TATGAC

TATGTGACTGATGATATCTTCTTTCTTTGTCAACAAGATATTTGATTCGATGTGCTA AAAAAAA

AAAAAM

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

11 GCTCTCTCTCCCTCCCTCCCTCCCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTAAACCCG ACG

CGATTTTCGAATCCGACCTCCCTCGACAACCCTCTCCGATGGCCGCCGCCGCACCGC CGC

CGTCCTCGCCGCGCGAGGAGTACGTGTACATGGCGAAGCTGGCCGAGCAGGCGGAGC GC

TACGAGGAGATGGTGGAGTTCATGGAGAAGGTGTCGGCCGCCGCCGCCGACGCCGAG GA

GCTCACCGTCGAGGAGCGCAACCTCCTGTCGGTCGCCTACAAGAACGTGATCGGGGC CCG

CCGCGCCTCCTGGCGCATCATCTCCTCCATCGAGCAGAAGGAGGAGAGCCGCGGCAA CGA

GGACCACGTGGCCGCGATCCGCGACTACCGCGCCAAGATCGAGGCCGAGCTCTCCAA GAT

CTGCGACGGCATCCTCGGCCTCCTCGACACCCGCCTCATCCCCGCCGCCTCCGTCGG CGA

CTCCAAGGTCTTCTACCTCAAGATGAAGGGGGATTACCACCGCTACTTGGCCGAGTT CAAA

ACCGGCACCGAGCGCAAGGAAGCCGCCGAGAGCACCCTCACCGCCTACAAAGCCGCT CAG

GATATTGCCAACTCTGAACTGGCTCCTACTCACCCAATTCGGCTTGGGCTGGCTTTG AACTT

CTCTGTTTTCTACTATGAGATTCTCAACTCCCCCGACCGTGCTTGTGGTCTCGCTAA ACAAG

CCTTTGATGAAGCAATTGCTGAGTTGGACACTCTTGGTGAGGAATCCTACAAGGACA GCACT

TTGATCATGCAGCTTCTCAGAGATAACCTGACCTTGTGGACATCCGACATGCAGGAT GATGG

AGTGGATGAGATCAAAGAAACAGCCAAGGCTGATGAGCAATAGTGATGTCTCAGCTG CTCA

TCAATATCCGTATAGAAGCTACCCTCTTATCTGTTTTTTAACTGGGGAAGATTGCTG GCTACT

GATTCATGTGCAATTCTGGGTTTTAGGCTCGTTGTCTCTATAACAGAATTCTGGTGT TGCTTG

TCTTATCGAAGTCTTATGTATTTCCAAATCACTCTTATTTCTCTTGGATTCTTAATG CTTCAAT

ATCTCAATTGAACACGATAAAAGGCCTCCATGTCTATGCAGATTGTTGCCTACTTTA AAAAAA

AAA

12 CTCTCTCTCTCTCTCTAATTTCCTTCACCTCAAACCCCCCCCCCCCCCAAATCCCACCGG CT

CCCGGCAGCAACCGCCGATCGCCGATCGCCGCCGCCGCCGCGATGAAGAAGGGGGGC TT

AAACCCCATCCTCAACCTCAAGCTCTCCCTCCCTCCTCCCGATGAGGACTCCATCGC CAAG

TTCCTGACGCAGAGCGGCACGTTCGTGGATGGCGATCTGCTCGTCAACAGGGACGGG GTT

CGGGTCGTGCAGCAGACCGAAGTCGAAGTGCCACCCCTTATCAAGCCAACAGACAAC CAGT

TGAGTTTAGCGGACATAGACACAATTAAAGTTATTGGAAAGGGGAATGGTGGAATAG TCCAA

TTGGTCCAACACAAATGGACTGGGCAGTTTTTCGCATTGAAGGTCATCCAAATGAAG GTTGA

GGAGTCTGCAAGAAAGCAGATAGCACAGGAACTCAAAATTAATCAATCTTCGCAGTG TCCAT

ATGTTGTGGTCTGCTACCAATCTTTCTATGATAATGGTACCGTTTCTATTATATTAG AGTATAT

GGATGGAGGGTCGCTGGCGGATTTTCTGAGAAAAGTTAAAACTATTCCAGAGCCAAA TCTTG

CGGTCATTTGTAAGCAGGTGCTCAAGGGTTTGTTGTATCTGCATCATGAGAAGCACA TAATA

CATCGAGATCTGAAGCCTTCTAATCTGTTGATAAATCATAGAGGAGAAGTCAAGATT ACTGAT

TTTGGAGTGAGTGCTATAATGGCTAGCACATCTGGACAAGCTAATACCTTTGTCGGC ACATA

TAACTATATGTCTCCTGAGAGAATCATTGGAAACAATTATGGTTACAAAAGTGATAT TTGGAG

CCTGGGCTTAGTATTGCTAGAGTGTGCAACTGGGAAGTTCCCATATACACCGCCTGA TCAAC

AAGAAGGATGGACCAATTTCTATGAGCTCATGGAAGCCATTGTTGATCACCCACCGC CTTCA

GCAGCTTCTGATCAATTCTCTAGCGAGTTCTGCTCATTTATCTCTGCCTGTGTACAG CAGGA

CCCAAAGAAAAGATGGTCTGCGAATGAACTTATGGGTCATCCTTTCATCAGCATGTA TGAGG

ACTTGAATGTTGATCTTGCTTCCTACTTCACTAATGCAGGCTCCCCGCTTGCAACCT TTTGAA

ACTCCACTGTGGTTCCAGCAACCGGAGATCTTTGGCTCCCTGGGAGCTTAGAGAGCA GTTT

CAAGAAAAACACCTGCTCAGGATTTTAATTTATTATGAAAGTGGATAACTTTTGGAG CTGATA

ACTGTCTGCCTCGAGCGGAGTGTAGTGGAGTGGAGTGAAGTGTTGGCAGTTAAAGAC GATT

TCAAGGGCGTGATTACTTTGAGCGTCGAAGGACAGCTGATGTAAATTCGAAATTTCT TTCTT

ATTGCAAGG

I ABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

13 CCGGCATTGCCCCGACCCGACCCGGCACGGATGGAGGACGACGAGCGGGGGGAGGAGTA

CCTCTTCAAGATCGTGCTGATCGGCGACTCCGCCGTCGGGAAGTCCAACCTCCTCTC CCGG

TTCGCGCTCGACGAGTTCGACATCAACACCAAGGCCACCATCGGGGTCGAGTTCCAG ACCC

AGGTCGTGGAGATCGACGGCAAGGAGGTGAAGGCCCAGATCTGGGACACCGCCGGCC AG

GAGCGCTTCCGCGCCGTCACCTCCGCCTACTACCGCGGCGCCGTCGGCGCCCTCATC GTC

TACGACATCACCCGCCGCACCACCTTCGAGAGCGTCAAGCGGTGGCTCGACGAGCTC GAT

ACTCACTGTGATACCGCTGTCGCAAGAATGCTTGTTGGGAACAAGTGTGATTTAAAC AATAT

CAGAGAGGTGAGCACCGAGGAGGGCAAAGCCCTTGCAGAAGCAGAAGGGCTATTCTT TAT

GGAGACCTCCGCCCTCGATTCCACGAATGTTCAGATATCGTTCGAGATTGTTATCCG CGAG

ATATACAAGAATATCAGCAGGAAGGTCCTCAACTCCGATTCATACAAGGCGGAATTG TCCGT

AAATCGAGTGACCCTCGCCAAAAACGGTGCGGACTCGTCAGGTCGGAGTTTCTACTC GTGC

TGCGCTAGATGATGTCCGATCCTTCATGTACGCTCCATCAATTTTTTGGAGTCTCTT GTACTG

TTTTATTTCATCAAATTTTTGGAAGTGTCTTGCACTGTCTTATTTTATCAATTTGTA TCCTAATA

CGTGGCCAATGAACTTTACGGTTTTCTTCAAAAAAAAAA

14 CGAGCACAGTCGGTGGTCAGACCACTTTCCCACGTCTTTTTCTCTTTCCTCCTCCTCCTC TT

CTCCTTCAATCCCCTCCGCATTCCAAGCGTCCGCTGCATTGGATCGACCTCTGACGG AACC

TGCAGAAGAAGCGAGAGACAGAAGAGCGAGAAAGCAGAGGGAGATGTCGTCGTCGGA CGA

GGAGGGAGGGGAGGAGTACCTGTTCAAGATCGTCATCATCGGGGACTCGGCGGTGGG GAA

GTCGAACCTGCTGTCCCGGTACGCCCGGAACGAGTTCAACCCCCACTCCAAGGCCAC CAT

CGGGGTGGAGTTCCAGACCCAGTCCATGGACATCGACGGCAAGGAGGTCAAGGCCCA GAT

TTGGGACACCGCCGGCCAGGAACGCTTCCGCGCCGTCACCTCCGCCTACTACCGCGG TGC

CGTCGGCGCCCTCGTCGTCTACGACATCACCCGCCGCTCCACCTTCGACAGCGTCTC CCG

CTGGCTCGACGAGCTCAAGACTCACTCAGACACAACAGTTGCAAGGATGCTTGTTGG GAAC

AAATGTGACCTGGAGAGTATTAGGGATGTGACGGTTGAGGAGGGGAAGAGTTTAGCG GAAT

CAGAAGGGTTGTTCTTTATGGAGACTTCCGCTTTGGATGCCACAAATGTGAAGACAG CCTTC

GAGATCGTGATAAAAGAAATATATAACAATGTGAGCAGGAAGGTTCTAAATTCAGAT GCTTAT

AAAGCAGAGCTCTCTGTTAACAGGGTAACCTTGGCTGGTAATGGGGCCGATGGATCA AAGC

GGAGTCAGAGCTTTTCTTGCTGTTCCAGGTGATACTGTAGAGGTGTAATTCTTTCAA GTCCG

ATGATGAAAACTTCATTGTCGATTCTATTGGTTGAGCTGTCTGTTTGTTTGGTTTTT GCTTGTT

TTTTCTTATCAGGGGTTTTTAAAATGCTGTTATAGCAAATTTTATTCAAGAATATTA ACCTATC

GATTTCTTCTAGTTCTAGATATATGTAATAGCAAAGAATTATGTGGACCAAAAAAAA AA

15 GAAAGATCGAGAAACCTGCTGCGGCTGCTAAGTGGGAGGACTAGCAGAGACAAACCAATT T

CCACACGTCTCTCTCTCTCTCTGCTCTCAGACCAGACGGCGACAAAACTGAGCTCCG GCTC

GGAGCGACAGCAAAACCCAAGCCACACAGAAAGAGAGAGATACACAGAATAGCAATG GCG

CTGGTTCCATCCGATCCCATCAACAACGGCCAGTCCCTCCCCCTCATCGCCGAGGTC AACA

TGTCCTCCGACTCCTCCTCCGCCGCCGCCGTCGTCCGCGCCACCGTCGTCCAGGCCT CCA

CCGTCTTCTACGACACGCCCGCCACTCTGGATAAGGCGGAGAGGCTGCTGGCCGAGG CGG

CTTCGTACGGGTCTCAGCTGGTCGTCTTCCCCGAAGCCTTCGTCGGCGGTTACCCCC GCG

GCTCCACCTTCGGCGTCAGCATCGGCAATCGTACGGCGAAAGGCAAGGAGGAGTTCC GCA

AGTATCACGCCTCCGCCATCGATGTTCCAGGCCCTGAAGTTGATCGCTTAGCAGCGA TGGC

TGGAAAATATAAAGTTTTCCTAGTGATGGGGGTGATAGAGAGAGATGGATATACATT GTATT

GCACAATCCTGTTTTTTGATCCTCAAGGTCATTACCTTGGGAAGCACCGTAAAGTCA TGCCA

ACGGCTCTGGAGCGTGTCATCTGGGGATTTGGTGATGGGTCGACCATTCCGGTGTTT GATA

CGCCGATTGGGAAAATTGGTGCGGCCATTTGCTGGGAAAATAGAATGCCACTTCTGA GGAC

AGCAATGTATGCTAAAGGTGTTGAAATATATTGTGCGCCGACAGCTGATGCGAGGGA CATTT

GGCAAGCATCTATGACACATATTGCTCTTGAGGGTGGATGTTTTGTTTTATCAGCCA ACCAA

TTTTGTCGTCGGAAAGACTACCCGCCTCCACCAGAGTATGTTTTTGCAGGAACAGAT GACGA

TCTTAACCCAGATTCTGTCGTATGTGCTGGAGGCAGTGTAATTATATCTCCATCAGG AAATG

TTTTGGCCGGACCCAATTATGATGGCGAGGCACTCATCTCAGCTGACCTTGACCTTG GAGA

AATAGCGCGGGCCAAGTTTGATTTTGATGTGGTTGGGCATTATTCGAGGCCTGAGGT GCTT

AGCCTGATCGTGAGGGACCATCCGAGCAACCCAGTTACCTTTGCATCGACATCCGGG AAGC

CTGAAGGCCCTTACAAATAGGTTATGTTTTCTTTCACGGAGCCAGGTCTGAATCATG GCAAA

TAACGGCAAGCAAATGTTGGTCCCAGTGGGAAGCTTTTGATTGTTTGTTTCAACTTT TTGGA

CTCCTGATTGTTTGTTCAACTTTTTCGACTTCATGAGCTATTGTAAATTCTGATTGC AAGCAA

CATAGTTCATGAATACTTCCTGCTTGATAGTTGAGAAAGCGATGTTATATTTCAGTT GCACAG

TAAACATGTCTGTATCCTGTGCAGTAGGACTCTTGTAACTAGTCTGTATCTTGGCAA TGAAAT

AAGAACATTAGTGACTGTTCTCGTGAATTAAAAAAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

16 TCTCTCTCTACACACTCTCTCTCTCTACATTCTTTCTCTCTCTTCACTTTCTCTCTCTAC TGTG

TCCCTGCCCAAATTGCCATTTCTGAAGTGTGTCAGCTTCGCCCTTTGGGTGGAGTTA AACAG

AGATCACAATAATCTCCTTCATTATTGTCATCTTGACATCGACTCCTCTCTCCCTCT CTCTCT

CTCTCCATCCATCTCCTCCTCGTTCTCTCTCTATATTACCCATTTCGCCTCCGTCCT TCCGTT

TCTCTCTCCTCCTCTCCTTCCCCCCCCTTTTCCCCCCAACCTCCAGTTCATTCGGCA TCACT

CACTCCCAATCTCAATCTCCCGGACCCATGTATCAAATCTGAATCTTTGCTCTCAAT TCCCAA

TCCCCGGTCGAATCTTTGACTACCCATCTTCGAATCCTCTTCTGGGTCGCCCTCTAT CTCCC

TCCCCACGTCCCCCGCCTCCGCCGCCGGAGCGGCCGGGGTTCTGCAGCCGAGGCCGC CG

CGACCGGCCGCATTGAGCCCGGAGCCGACCGCCGTCCGCCGTCCGGGACCGATCCGG AG

CGCAAAGTCATGAGCTTGGCGGGGTCTTGGTGATTCCCCGGGAGGTGGGTCGGTCAT GGA

TCCGAGCAAATCGCGCGACTCGGCGGAGTCGACCCGGGTGATACAGTTCCCGAACGA CGT

GCTGGAGCGGATTCTGTCCCTCATAGACTCGCACCGGGACCGGAACGCCGTCTCCCT CGT

CTCCAAGGCGTGGTACAACGCGGAGCGGTGGACGCGGCGGCACGTCTTCATCGGCAA CTG

CTACGCGGTGTCGCCGCAGATCGTGGCCCGCCGGTTCCCCAACATCCGCAGCGTCAT GCT

CAAGGGGAAGCCCCGGTTCTCGGACTTCAACCTGGTGCCGCCCAACTGGGGTGCTGA CGT

ACACGGGTGGCTCGCGGTCTTCGCGGATCAGTACCCGCAGCTCGAGGAGCTGAGGCT CAA

GCGGATGACCGTGACGGACGAGAGCTTGAAGTTCTTGGCTCGCAAGTTCCATAATTT CAGG

GTGCTCTCGCTCCTGAGCTGCGATGGGTTCAGCACCGATGGTCTCGAGGCAATCGCA ACC

GACTGCAGACATTTGACTGAGCTGGATATACAAGAGAATGGGATTGATGATATCAGT GGCAA

CTGGTTGAGTTGCTTCCCTGAAAACTTCACATCTATGGAGGTGCTGAACTTTGCAAG TCTAA

GTAGTGATGTGAATTTTGACGCTCTTGAGAGGCTTGTAAGTCAGTGCAAGTCACTGA AGATT

TTGAAGGTTAATAAAAGTATTACGCTAGAACAATTACAGAGGCTGCTTGTCCGTGCT CCTCA

GTTGACCGAGCTTGGTACTGGTTCGTTTTTACAAGAGCTTACTGCTCACCAGTCTGA GGAGC

TTGAAAGAGCTTTCATTGGTTGCAAGTATCTGCATGCACTCTCCGGCTTGTGGGAAG CTACG

ACACTATATCTACCTGTTCTTTACCCAGCCTGTACAAATTTGACTTTTCTGAATTTA AGTTATG

CTGCTTTGCAAAGTGAAGAGCTTGCCAAGCTTGTTGCCCACTGTCCACGTCTTCAGC GTCTC

TGGGTACTTGACACTGTTGAAGATGTAGGACTTGAGGCTGTTGCCTCGAGTTGTCCC CTTTT

AGAGGAGCTTCGAGTCTTCCCAGCTGATCCTTATGACCAGGACATTAATCGTGGTGT GACT

GAATCGGGGTTTCTTGCTGTGTCGCTCGGCTGCCGCAAGCTCCACTATGTCCTCTAC TTTTG

CCGTCAGATGACAAATGCTGCTGTAGCCAGAATTGTGCAGAACTGCCCTGGTTTTAC CCACT

TTCGTCTTTGCATAATGAAGCCGGGGCAACCTGATTACCTAACAAATGAACCTATGG ATGAG

GGTTTTGGTGCAGTTGTGAAGACTTGCACAAATCTCCGAAGGCTTGGCGTTTCTGGT CTTTT

GACTGACTTAACGTTCGAGTATATTGGAAGATATGCGAAGAACTTGGAAACGCTTTC TGTGG

CTTTTGCTGGCGGCAGCGATCTCGGGATGAAGAGTATACTGGTTGGTTGCCCAAAGT TGAG

GAAACTTGAAATAAGGGATTGTCCATTTGGTAATGAAGCTCTTCTTTCGGGCTTGGA GAAAT

ATGAGTCAATGAGATCTTTGTGGATGTCTGCTTGCAAAGTGACGCTACATGGTTGTA AGACA

TTGGCTACGCAAAGGCCACGGTTGAATGTTGAGGTAATGAAGGATGAGGAGATCGAT GATG

GCCAGTCTTATAAGGTTTATGTTTACCGTACTGTTGCTGGACCAAGGACAGATGCTC CATCT

TTTGTCCATACTCTTTGAAGTTGATAATTAGAGGGAGCTGGTGCCAGGATTCTGGAA CTTTC

AAGGGCAGCCTGTGTTCTGCGAAGTCAGCCCTTGTGCTAATGCTGGAGCCCGGGGAG CGG

AACAGAACTCATGTTCCTGTTACCTCAACTGTTTTACAAGGCCTCCACCTGTGGTGC TCAATT

TGTTGTAGCAAGGCACCTTGAAATTTAACTTCTTGTAGACTCGTGAAATTTCCTTCC TTTGTC

ATATTTTCTTCTGAGTGTTTTTTAACTC

IABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

17 GGAGAGATAGAGAGAGCGAGAGGAGAGAGACGGCGATGGAGGATGAGGAAGAAGAGACG

ACGACGACGACGATGATGCGCGGACCATGCCGATCCAGAGACGGCGGCGCAGCAGCG GC

GGCGGCGGCGGAGGCGGCGGGGCCTTCCACCGTGTGTTGACTTCTCTCTCCCGGCCC TC

CCGACTCCGCCTTCGGGCTCGGCGGACTTGATTAGTCGGGCATGTGAAAAAGAATCT TTGA

CTGCTCAGATTGTTGAACAACGTGATGGAGTCCTGCAACTGCGTTGAGCCACAGTGG CCAG

CTGATGAGCTTTTGATGAAGTATCAGTACCTCTCAGATTTCTTTATTGCTCTGGCGT ACTTTT

CCATCCCTCTAGAACTCATCTACTTTGTCAAGAAATCTGCTGTATTTCCCTATAGAT GGGTTC

TTGTTCAGTTTGGTGCCTTCATAGTTCTGTGCGGAGCAACCCACCTGATCAACTTAT GGACA

TTTGCCATACACTCAAGAACTGTAGCATATGTTATGACCATTGCAAAGGTTTTAACT GCTGCG

GTATCATGTATTACAGCTCTCATGCTTGTGCATATCATCCCCGATCTACTTAGTGTG AAAACC

AGGGAACTATTTCTGAAAAACAAGGCTGCAGAACTTGACAGGGAAATGGGCTTAATT CGTAC

TCAGGAGGAAACTGGCAGACATGTCAGGATGCTAACGCACGAAATCAGAAGCACTCT TGAT

CGACATACTATTTTGAAAACTACTCTGATTGAACTGGGCAGAACTTTGGGATTGGAA GAGTG

TGCCCTGTGGATGCCAACACGAAGTGGCTTGGAGCTTCAGCTATCCTACACTCTCCG TCAG

CAGCAGAATCCAGTTGGATACACAGTACCCATTCATCTTCCTGTAATCAATCGAGTG TTTAGT

AGCAATCGTGCGTTGAAGATATCACCCAATTCACCCGTTGCTAGAATACGTCCTCTT GCGGG

GAAATACATTCCCGGTGAGGTTGTCGCTGTGCGGGTTCCTCTGCTGCATCTCTCTAA TTTCC

AGATAAATGACTGGCCTGAGCTTTCAACGAAACGGTATGCTTTAATGGTGTTGATGC TTCCA

TCCGACAGTGCTAGGCAGTGGCATGTCCATGAACTGGAGCTCGTTGAAGTGGTAGCT GATC

AGGTTGCAGTTGCTCTCTCCCATGCTGCAATACTAGAAGAGTCTATGCGGGCAAGGG ATCT

TCTCATGGAGCAAAATGTTGCACTTGATCTGGCCAGAAGAGAAGCGGAAACAGCTAT TCGT

GCTCGCAATGATTTTTTGGCTGTTATGAACCATGAAATGAGAACTCCCATGCATGCA ATTATT

GCCCTTTCTTCCTTACTGCAGGAAACTGAACTGACCCCTGAGCAGCGTCTAATGGTT GAAAC

GATAATGAAGAGCAGTAATCTTTTGGCTACTTTGATAAATGATGTACTAGATCTTTC GAGGCT

TGAAGATGGAAGCTTTCAACTTAACATCGCCACGTTTAATCTTCATGCTGTGTTTAG AGAGGT

CCTTAATTTGATTAAACCGGTGGCATCTGTGAAGAAACTGCTCATCACATTGAATTT AGCCCC

AGATTTGCCTGAGTATGCTGTTGGGGATGAAAAACGCCTCATGCAAGTCATTTTAAA TGTTG

TTGGTAATGCAGTTAAATTTTCTAAAGAAGGTGGCATTTCGATAACCGCCTTTGTGG CTAAAG

CAGAGTATTTAAGAGAAGCCAGAACTCCCGAATTTCTTCCATTGCCAAGTGATAATC ACTTCT

ATTTACGTGTACAGGTGAGAGATTCTGGATCAGGTGTTAACCCTCAAGATATTCCCA AGTTA

TTCACAAAATTTGCACATAACCAATCATTAGCAACCAGAAATTCTGGTGGGAGTGGA CTAGG

TCTTGCAATTTGTAAAAGGTTTGTAACTCTCATGGATGGACACATATGGATTGAAAG CGAAG

GCATTGGCAAAGGATGTACTGCCACGTTTATTGTAAGGCTGGGAATCCCAGAGAAGT TGAAT

GAATCTAAGTTCCCTGTATTACCCAGAGGGTCATCAAATCATGTCCTGGCCAATTTT TCTGG

GCTCAAAGTGCTTGTTATGGATGATAATGGTGTTGGCAGGGCAGCGACCAAGGGACT TCTC

CTACATCTGGGATGTGATGTGACAACCGTAAGCTCGGGGGATGAGTTGTTGCATGCT GTCT

CTCAGGAACACAAGGTAGTTCTTATGGATATTTGCACGCCTGGTATAGACAGTTACG AAGTT

GCCGTCCAGATACACAGGTTGTATTCACAACATCATGAGAGGCCACTCTTAGTGGCA ATCAC

TGGAAGCACTGACAAGGTAACCAAAGAGAATTGCATGAGGGTTGGGATGGATGGTGT TATC

CAGAAACCTGTGTCGCTTGATAAAATGAGAAACGTACTGTCTGAGCTACTGGAATGT GGACA

TCAAATGTCTAGTTTGGCCCGTGTTTGAGAAGAATGGAGAAAATAAGACTGCGATAA AGTTT

CTTGCGGCAAATGATTTGTAAATACTGCATGCAGTGGAACATTGGAGGGTTATCAAG CAATG

CTACAACAACCCCATGTAATACGAGACTCATACCGATCATTTTTATCCAAGAATGAC CAAGGT

CATCAGATGATTGAACAAGCCGAAGCCCCATAGTGGAGCTGCTAGTAACTTCACGGG ATGA

TGACAAGTCTTATGTGTCGTCGACAAAGTTGTGATGTCGTTGCAATTGTAAGATATT ATGGTC

CCATCAATGATATCTCTTTGTTTGAAAAAAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

18 GAAAAGCTTCTGTACATGCGCAATCCCAAAGGAAGCCCTCTGAACATCCGTTGATCCCTG G

CGGAAAAAAGAGGCAGCACCCATTGATCACCAGGGAGAAAGAGAGAGAGGGTTGCTT ACG

GATTCTCCGAATTCGCAAGAATGGCTTCTCGGAGACGCATGCTTCTCAAGGTCATAA TCCTT

GGTGACAGCGGGGTTGGAAAGACATCTTTGATGAATCAATATGTGAACCGAAAGTTC AGTAA

TCAGTACAAAGCAACCATCGGGGCAGATTTCCTTACCAAGGAAGTCCAGTTTGGGGA TAGA

CTTTTCACATTGCAGATATGGGATACAGCGGGGCAGGAACGGTTCCAAAGTCTCGGT GTTG

CCTTTTACCGTGGAGCTGACTGTTGTGTTCTTGTATATGATGTGAATGTGATGAAAT CGTTTG

ACAACCTTAACCACTGGAGAGAGGAGTTTCTCATTCAGGCCAGCCCTTCTGACCCTG AGAA

CTTCCCATTTGTTGTGTTGGGAAACAAGATTGACATTGATGGTGGCAACAGTCGAGT GGTAT

CTGAGAAGAAAGCGAAAGCATGGTGTGCCTCAAAGGGAAACATTTCTTACTTCGAAA CTTCT

GCAAAGGAAGGTTTTAATGTTGAAGCAGCTTTCCAATGTATAGCCAAGAATGCCCTT AAGAA

TGAGCCTGAAGAAGAACTCTACCTTCCCGATACTATTGATGTGGCTGGTGGACAGCA GCAG

CGTTCTTCGGGCTGTGAATGTTGAAGAGTATATGACTTTAAATTTGCTGGTCCCTCG AGAAA

AGACTCGCAAAAGACGGCCATCATTTTACTTCTGCCGACTGTGAATCGCCAGGGCAC TACC

GGTTGTTGAGAGTGCCATGTATATCATTAGCAATGTTCATCAGTTCAGCACAATATT TGTGGT

TTCATCGTTCCAAAATCGTGCGTTGTGAAATTGGTTGTGTATAATCTCTAGAATCCA AAGGCT

TACGGGTCATGCAATCCTTTCTAATTTGATTACTCAGATGTCCAAGCTGTACACTTA ATTTGC

TCTCAAAAAAAAAA

19 GGTCGAAGCTGAAAATCTGACAAAATCCTCTCCCCGCGGCCGTTTCCGTTCTTGAGCTTC G

ATCCGCAGGGAAGGGGAGCTCCGAGCAATGGCGGGCGGCTACAGGGCGGACGACGAC TA

CGACTACTTGTTCAAGGTGGTGCTGATCGGCGACTCCGGCGTCGGCAAATCCAACCT CCTG

TCCAGATTCACGCGGAACGAGTTCAGCCTGGAGTCCAAGTCCACCATCGGGGTCGAG TTCG

CCACCAGGAGCATCCGCGTCGACGACAAGGTCGTCAAGGCCCAGATTTGGGACACCG CCG

GCCAAGAGAGATATCGTGCAATCACAAGTGCCTATTACAGAGGAGCAGTTGGTGCAT TGCT

TGTTTATGACGTTACGAGACATGTCACTTTTGAGAATGTCGAAAGATGGTTGAAGGA GCTGC

GGGACCACACAGACTCTAATATCGTGATAATGCTGGTAGGAAACAAAGCAGATCTGA GGCA

CTTGCGTGCCGTGTCTACGGAGGATGCCAAGGCCTTTGCAGAAAGAGAGAACACTTA CTTC

ATGGAGACTTCCGCTCTTGAATCTATGAATGTAGAGAATTCATTCACCGAAGTGCTC ACACA

AATATACCACGTGGTGAGTCGAAAAGCACTTGATGTTGGGGAAGATCCGGCAGCACC TCCC

AAGGGACAAACTATCAGTGTCGGTTCAAAGGATGATGTTTCCGCAGTCAAGAAAGTG GGCT

GTTGCTCCGCTTGAAGTTAAGAGTAACAGAATGAAGATTTTGGGGGAAGTCTTTATT CAATC

CTAATCTGCTGCCCGGAGAATTGGAAGATGTTACGCGGGAATTGCAGACCTTCTTTA CAACC

TGTCACCATCATCTCCATGCATGGCGATGCTTAAGCTTTTGCCGGATCAATTTAAGT TTGAA

GTCCAAGGAAACCGGATGTTAGGGCTTCGTGTATTTCATTTGTTTCATTTCCAGATG CTTAAT

TTTCTATTCCCATCCCGTGTTGATTTGTTTGTTGGGTTCTCTAGGTTTTTGAGCTGA ATTGGT

CATGTCACACAGGGAACTGTCTTCGGGCGAGTTTAATCATGTATCTGATTTACGATC GGTGT

TGTGAACGTCGGA

20 CACCAACCATCCCGGGCGGGCGGCCTCGACTCCTTCTTGTTCCGTGCAGTTTTCATAGAC T

ACTTCCATTAACGAGAATCCTTCCTCCATCGGCGTCTCCTTCTCCTTGTGCTTCTTG TTCTTG

GTGAGACTCTTGGAAAAGGGATGGTGGATTCGTTCGACGAAGAGTGCGATTACTTGT TCAA

GGCCGTCTTGACCGGGGACTCTGCCGTCGGGAAATCGAATCTCCTATCGAGGTTCGC GAG

GAAGGAGTTCCAGTTGGATTCGAAACCCACGATAGGCGTCGAATTCGCATACAGGAA CGTC

AAGGTCGCCGACAAGCTCATCAAAGCCCAAATATGGGACACTGCAGGGCAAGAAAGA TTTC

GAGCCATCACCAGTTCATACTATCGCGGAGCACTGGGGGCGCTGCTGGTTTACGACA TCAC

TCGGCGAGTGACGTTCGAGAACGTGAAGAAATGGCTGCGCGAGCTCAGAGACTTTGG GAA

TCCCGACATGGTGGTGGTCCTGGTCGGGAATAAGTCCGATCTGGGCAGCTCTAGAGA AGT

GGACCTGGAAGAAGGGAAGGACTTTGCGGAGGCAGAGAATCTGTGCTTCATGGAAAC TTCT

GCTCTGGAGAATCTAAATGTCGAGGAAGCATTCTTGGAGATGATCACCAGAATCCAT GAGAT

CACAAGCCAGAAGAGCTTAGAAGCCAAGAACAATGAAATAACCAGTAGCCTTCACGG TCCT

AAGCAGGTCATTCAGATTGATGAGGTCACTGCTACTAAAAAGCCATACTGTTGCTCA AGTTA

ATCCCAACCGTTGGGGGATTTTTTGACGAGTCAGTACCAAATTTATAGTTGCCTACT GACCA

CATCTTGATTTTTTTCCCCTGAATTCAAGTCCAATCAGCTTCCTCTTTAAAAAAAAA A

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

21 GGTAATTGCCCAAATCAGATTCCTAGATTCTAGCCAACTCGACAACCGTCTCCACCCTTT CT

TTCTTCCCCTCAAATTTCAAATCAGTCCAAAAAAACTCAAGACTGCTGCTGCTGCCG ATTGAT

TCGCCATCTCCTTCCCACCTTCCCTCCTTCCTCTCCAATCTCTCGAAGCTCCGTTGC TTTCAT

GGCCGGGTACAAAGCCGACGAGGAGTACGACTACCTGTTCAAGCTGGTCCTGATCGG CGA

CTCCGGCGTCGGCAAGTCCAACCTTCTCTCCCGCTTCACCCGGAACGAGTTCAACCT CGAG

TCCAAGTCCACCATCGGCGTCGAGTTCGCCACCAAGAGCTTGAGCATCGACGGCAAG GTC

GTCAAGGCCCAGATTTGGGACACCGCCGGCCAAGAAAGGTACCGTGCCATCACTAGT GCTT

ACTATAGAGGAGCTGTTGGCGCTTTACTTGTGTATGACGTCACCAGGCGTGCGACTT TTGA

GAACGTTGCAAGGTGGCTGAGGGAGTTGAGGGACCACACCGACCCCAACATCGTGGT CAT

GCTCATTGGCAACAAGTCTGATCTTCGCCACCTTGTGGCAGTCCCACTGGAGGATGG GAAG

TCATTTGCCGAGATGAGTCACTACTATTTCATGCAGACTTCTGCATTGGACGCGACC AATGT

GGAAGCAGCTTTTGCTGAAGTCCTTAGTCAGATTTATCGGATTGTGAGCAAGAGAGC AGTC

GAAGCGGGTGACAACCCAAGTGTTTCTTCTGTTCCAGGTCAGGGACAAACGATCAAT GTCA

AAGAAGAGGGGTCTGTTTTTAAGAGGATTGGATGCTGCTCTAGTTAAGGTAGGTTTC TTCGG

CTGCTTGTTGCTCCAAGGGTGGGTCTGCCAAGTGCTACCTCTGTGTATATTTT

22 GGTCATTGMGTCTMTCATCTTCMCCTCTCACCGMCAGACGCTGCTGCTGCTCTCTCCT

TCTTTCCCCTTCCCCATCMCACGCTCGTCTCTGTCCCTGTCCCTGTCCCTGTTTCTC TCTCT

ACCCTCCGAGATCTCCACAGTAGAGAGAGAMGACAGAGAGAGAGAGAGAGAGAGAAG TG

ACGTGGTGACAGTAGAGAGAGAMAGACCCGAGCTTGAGTCGTGGGTCGGTCGTGGGC M

TGGCGAGCGGAGGAGGCTACGGGGACGGGMCCAGMGATCGACTACGTCTTCMGGTGG

TCCTGATCGGGGACTCCGCCGTCGGGMGTCCCAGATACTCTCCCGCTTCGCCCGCMC G

AGTTCAGCCTCGACTCCMGGCCACCATCGGCGTCGAGTTCCAGACCCGGACCCTCGT CAT

CCAGCACAAGAGCGTCMGGCCCAGATCTGGGACACCGCCGGCCMGMCGATACAGAGC

TGTTACGAGTGCATATTATAGGGGTGCGGTGGGGGCAATGCTTGTTTATGACATTAC CAGAC

GGCAGAGCTTCGATCACATACCTCGCTGGTTGGMGAGCTGCGTAGCCATGCTGACAA GAA

CATTGTCATTATTCTGGTCGGTMCAAMCCGATCTCGAGAACCAGCGTGCCGTGCCCA CT

GAGGACGCGAMGAGTTTGCCCAGMGGAAGGGCTCTTCTTCTTGGAGACCTCTGCATT GG

ATTCTACCAATGTCGAGAGTGCATTCTTGACTGTCTTGACCGAGATATTCMCATCGT CMCA

AGAAGAGCCTAGTTGCTGGAGAGAGCCAMCTAATGGCAATCCTGCATCTTTGGCTGG CM

MAGATCATCATCCCGGGTCCTGCCCMGMATCCCAGCCMGMCMAATGTGTTGCGGA

ACATAATGCACTTCGACGTGATTTTCCTCTTATGCTCTAGCAATTTTTCCTCAGATT TGTCAT

GTGTGCTGCTTTATATTCTATGTATATCTACATATTAGAAGAGTGGTGGGGTTATAC TGCTGA

TTGTMTAGTGTGTTTCGTGAGGTCACAGACACMTAGACCTMCTGGGGTGCATATTCA TT

GAATGATTTTTGGCTTCGGAAGTTATATTTCATGCAATTTGCCAAAAAAAAM

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

23 GTACGTTTCTAGAGAGAGAAAGTGAAGAGAGAGGATAGAAGAGAAGAGAGAGAGAGAGAG

AGAGAGAGCGCTGAGGAGGTTAGAGGTCATGGCTGACGCCGCAGCTCAGAACGGCCA GTT

CAGCGACTTCCCGGCGGTCCCGACCCACGGCGGCCAGTTCATCCAGTACAACATCTT CGG

CAACCACTTCGAGATCACGGCCAAGTACCGGCCGCCGATCATGCCGATCGGCCGCGG CGC

GTACGGCATCGTCTGCTCTGTTCTGAACTCGGAGACGAACGAGATGGTGGCGATCAA GAAG

ATAGCGAACGCGTTCGACAACCACATGGACGCCAAGCGGACGCTCCGCGAGATCAAG CTG

CTCCGCCATCTGGACCACGAGAACGTTATTGGCATTAGAGATGTGATTCCTCCTCCC CTACG

GCGAGAATTTACTGATGTCTACATTGCTATGGAACTCATGGACACTGATCTTCACCA AATTAT

TCGTTCAAACCAAGGCTTGTCAGAAGAGCACTGTCAGTACTTCTTGTATCAGATTCT ACGTG

GACTGAAGTATATCCACTCTGCGAATGTTATTCATAGAGACTTGAAACCCAGCAATC TTTTGC

TGAATGCCAATTGTGACCTGAAGATCATTGACTTTGGCCTGGCACGGCCAACTGCAG AAAAT

GAATTTATGACTGAATATGTGGTCACCAGATGGTACAGGGCACCAGAATTGCTGTTG AACTC

TTCAGATTATACTGCTGCTATAGATGTGTGGTCTGTTGGTTGCATATTTATGGAGCT TATGAA

CAGAAAGCCTTTGTTCCCTGGGAGGGATCATGTGCATCAGATGCGTTTGCTTGTAGA GCTTC

TTGGTACACCAGCTGATGCCGATCTTGGGTTTGTGCGAAATGAGGATGCACGCCGAT ACAT

AAGACAGCTTCCTCAGCATCCCCGTCAACCATTGGCTAGTGTTTTTCCTCATGTTCA CCCTTT

GGCCATCGATCTGGTTGAGAAGATGTTGACATTTGACCCAACAAAGAGAATCACAGT TGAAG

AAGCACTCGCCCATCCTTATCTTACGAGATTACACGACATAGCTGATGAACCTGTGT GCCGA

CAACCATTTTCTTTTGAGTTTGAGCAACAGCCCTTGGGAGAAGAGCAGATGAAGGAC ATGAT

ATATCAGGAGGCTATAGCGCTCAATCCAGAGTTTGCTTGATGCTGTTTAAAGTTTCT ATGGT

GGATGAGGAACTGCGAACTAAAGTGGAAACAGTGCAGCGCAACGAAATGAAGAGTTG CACA

TATTCAGAGGCAACCGATCTCGTTGCTTTATTTTTCCGTGGAGTAAGTATGCCGTAC CACGA

ATACTGATTTGAGGGGAGCTTTGCTCCACCTGTCGAATAAACTTTCTTGATTCCTTG AAACG

CCTTTTGTTTTTGCAATCGGTGCTTCTTGGCATTCTTTTATTAGCTTGTATTTCACT CAACGTG

CTTAATATCATTTTGTTGTAACATTTCACAGTTTGTAAATTTGTACTGCAAGATGTA TTAGTAA

GAAGAACTGTATTTTTTTTTATTTTTTTGGTTCATTGAACCGTGCTTCAGTTTATGA ATGCTAA

TCTGTATGTAACGCGCAGAGCAGGGCGCTAGAGCTTTTATCTGTGCCTTCACAACTT CTGTT

TTATTATAAATCCCTTCGTTCCCAAAAAAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

24 TTCTCGATAAGCAATAATTGCTGCCCTTCTCTTTTCCTCGTCACTGCTACAGAGGCCGGG TC

TAATCGCGACGAGGTGACGAATCTGAGATCGAAAGTCGTCTCCTCTTGTTGCGGGGT CAGA

TCCGTAGGGCTCGTGGCTTGACAAGAACAGTGCTTTCCGAGGGAATAAGCAGATCCC AATG

CGTTAGGGGAATGATTGCGTAGGGCTGCGATCTTGGGCATCTGTTGCTGTCGGGAAT TCTT

GCGAGGAGAAGGGCCTCTGAGGCTGCGTCGTGCTGGGGAGTTGATGAATTGCGCCTG CTC

GGGGGAAGAGTGAGTGGGATCCGACGATGGGTCTGAGCAAGAATGGCTTCTTTCTTT GAAT

TCGCTTCGAAGATCACATAAAAAGCAAATGGCAACACTAGTTGAGCCGCCAAATGGG GTTCA

TTCCGAGGGAAAGCACTATTACTCGATGTGGCAGACCTTGTTTGAGATTGACACAAA GTATG

TGCCCATCAAGCCCATTGGCCGGGGAGCCTATGGCATTGTTTGCTCTTCTGTGAACA GAGA

AACCAATGAGAAGGTGGCTATAAAGAAAATTCACAATGCCTTCGAGAATCGGGTTGA TGCGC

TGAGAACTTTGCGCGAGATAAAGCTTCTCAGGCATCTTCGGCATGAGAACGTCATTG GTCTG

AAAGACGTCATGATGCCTATCCAGAGGAAAAGTTTCAAAGATGTCTATCTGGTGTAT GAGCT

TATGGACACAGATCTGCACCAGATAATCAAATCCTCTCAGACACTTACGAATGACCA CTGCC

AATATTTCCTCTTCCAGTTGCTACGAGGCTTGAAGTATCTACATTCAGCAAACATTC TCCACC

GAGACTTGAAGCCAGGGAACCTTCTCATCAATGCAAACTGTGACCTCAAGATCTGCG ATTTT

GGGTTGGCACGAGCTAGCAATGGAAAGGGACAGTTCATGACTGAGTATGTGGTCACT CGCT

GGTACCGGGCCCCAGAACTCCTTCTGTGCTGTGACAACTACGGCACATCCATCGATG TGTG

GTCTGTTGGATGCATCTTCGCTGAGCTTCTCGGACGTAAGCCATTATTCCCTGGTAC TGAGT

GCCTCAACCAACTCAAACTGATCATCAATGTCCTCGGCAGCCAAAGAGAGGAGGATA TCGA

ATTTATCGACAACCCAAAGGCGAAAAAGTTCATAAAGTCTGTCCCATATTCCCCAGG GACTC

CATTATCCCGTCTTTACCCTAATGCACATCCTCTGGCTATTGATCTCCTGCAAAAGA TGCTCA

TTTTCGACCCATCAAAGCGCATTGGCGTCACTGAGGCTCTCCAACACCCATACATGT CACCG

CTGTATGATCCGAATACCAATCCTCCTGCGCAGGTTCCCATCGACTTAGATGTCAAT GAAGA

TCTGGAGGAAGAGATGATAAGGGAGATGATGTGGAAGGAAATGCTCCATTACCATCC CGAA

GTCGCTGTGGGCAATTTAGAGGTGTACTCTTAAGCATTCTTCAGTTGTTTTGTCTCG CCTCT

CTGTGATAAGGTACTCCATCAATATGCTGCTGCACTTCATTATGATGGTTCTGTAGT TTCTCT

TAACATATAGGCTAGCTTTTCCTCTTTTTCTCAGAGAGGGGATAAAATAATTTGCTG GAATCA

TGCCCAGGAAGTTCTTGTCCTCAAAATGCATGATTGAGCAACCGTTATCTTTCTTCT TCACTA

TGTCTGTTTGAGATCCATGTACTAGGTTTCCTATCTAACCTGTAAATAGCCTTATTG CTATGA

GACTTCAGGCTTGTTGTACAATTATATGATATGCTTGAGGATGCTTTTATAACATCT GGTTTG

GACGTAATAAGAGTACTTCTAAAGCTGTAAAAAAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

25 GCTCTCTCTTCGTTCGCTTCACTGCCCCCCTCTCTCTCTCTTTCTCTCTCTCTCCTCGAG CTG

AGCTCAACTCGAACAAGAGCATTGCGGTTCACACAGAGGAGGGCAGAGGAGAGAGAA AGA

TAGAGAGAGAGAGAGAGAGAGGAGGAGGAGGAGAGAGAGAGCTCTGCATATTCAGGG TCA

TTGAGGAGATTTGTATCTACTTATGGAGATTGTAGATTCTGCGATCTGAGAAATTCG GGAGC

TCTGCTTATCTTTTTCTCTTCCTGTCTTGTCTTTTTTGTTTGTTTTTTCGTTTTTTT GGGTCTCC

CTCTTCTCAGCTGCTGCTGCTTGCTGCAGCTGCTGCAGCAATCATCATCATGACTTC TTGAT

TCGTAGATGATAGGTGAAGAAGAAGAAGAAGAAAGGGGGGGTTTTTCTCTTTCTCTG CTCTC

TTTCCTAGCTCTCTGCTCCTTACCCAGAAAGCCGTTCGTTCTCTCTCTCGGGCCGGA ATTTG

CTCAGCGTCTGTCTTTTCCTCTCTCCGTTCAGATCTAATCGGAATCGGGAAGATATG TAAGG

GGGGGTCTTCTGGGTTTTGTCCGTCGCCATTTCCTCTCGAGCCTCGCGCGGTTTTAA GCGT

TTAGATCTGGGTTTTTCTTAGCTGGGTAGGTTTGGATTCAGTTCGCAGGTTGTAGTA GCTTA

ATCTCTGTACATTTGTTTTTTTTTTTTTTTTTTTTTTGTCTCCGAGCTATTTGGTTC TTTTGGGG

CGAAGGGTTGTGTTGGGATTAGGTTGTTTTTGCCGCCCCCCGGCTGTTTTTTTCGTT AGGGT

TTCTGTTCTTTTTTCTTCTTTCTTCCTGCGGGAGGGATGGATTGAGGGCTCATTTCG TTTGAA

AGTTGGGATTTTTTTTTTCCTGGGCAGTCGTGGGAATTGGATTTGTCACTTGGGTAA GGGAA

GATGAATTATTTTCCCGATGAAGTTATCGATCACGTGTTCGACTTTGTGACGTCGAA CAGGG

ACCGCAACGTGATCTCTTTAGTGTGTAAATCTTGGTATAGGATCGAGAGGCTTAGCA GGCAG

AGAGTGTTTATCGGGAACTGCTACGCGATAAGTCCTGAGAGATTGATCGCGAGATTC CCGG

GGGTAAGGTCGCTCACTTTGAAGGGGAAGCCCCATTTCGCTGACTTCAATCTAGTGC CACC

TGACTGGGGAGGGTTCGTGTACCCTTGGATCGATGCATTGGCTAGGAGTAAGGTTAA TTTG

GAGGAGCTCAGGTTGAAGAGGATGGTGGTTACAGATGATGGTCTTGAGCTGATTTCG AGAT

CGTTTGTAAATTTCAAGTCCTTGGTTCTTGTTAGCTGCGAAGGGTTCACTACTGATG GCCTT

GCGGCTATAGCAGCCAACTGTAGGTTTCTTAGGGAGCTGGACTTGCAAGAAAATGAA GTTG

AGGATCATAGAGGCCAGTGGCTAAACTGCTTTCCCGATAGCTGCACCTCTCTTGTCT CCCTA

AATTTTGCATGCTTAAAAGGAGATATAAATTTAGCAGCACTTGAGAGGCTTGTGGCA AGATC

TCCATATCTCAAGAGCTTGAGGCTAAGCCGTGCTGTCCCTCTTGACACGCTGCAGAA GATC

CTGGTCCGAGCACCTCAGTTGGTGGACTTAGGCGTGGGCTCTTTTGTCCATGACCCA GATT

CTGAAACCTACAACAAGTTGGTGACAGCAATTGAAAAATGCAAATCTATGAGGAGCT TATCC

GGATTCTTGGAGGTTTCTGCGTACTGCCTACCAGCTATTTATCCAATATGTTCAGGC CTGAC

CTCCTTGAATCTTAGTTATGCTCCTGGGATCCCTGGAAGTGAGCTAACTAAGTTAAT CCGTC

ATTGCAGAAAGCTGCAGCGCTTATGGATACTTGACTGCATAGGAGATAAAGGGCTGG GAGT

CGTGGCTTCAAGCTGCAAAGAACTACAGGAATTGAGGGTTTTTCCGTCTGATCCTTA CGGAG

TTGGAAATGCTGCAGTGACCGAAGAAGGGTTGGTTGCTATTTCCAGAGGTTGTCCAA AGCTT

AACTCACTGCTGTACTTCTGCCAGCAGATGACAAATGCTGCCCTGAAAATTGTAGCC CAGAA

CTGCCCTAATTTCATACGGTTCAGGTTGTGCATCCTCGAGCCCACAAAACCGGATTC TTCAA

CCAATCAGCCTCTTGACGAAGGATTCGGAGCTATTGTTCAGTCATGCAAGGGTGTCA GGCG

CTTGTCACTTTCTGGCCTTCTTACTGACCAGGTCTTCAATTATATTGGCACATTCGC TGAACA

GCTTGAGATGCTTTCTATTGCATTTGCTGGGGACAACGACAAGGGAATGCTTTATGT GTTAA

ATGGGTGCAAGAAGATTCGGAAATTGGAAATCAGGGATTGCCCCTTTGGTAACATCG CACTT

CTGACGGACGTGGGAAAGTATGAAACAATGCGATCCCTTTGGATGTCGTCGTGCGAT ATTA

CCCTTGGAGGCTGCAAAACCCTGGCAAAGAAGATGCCGAGGCTGAACGTGGAGATTA TCAA

TGAAAACAATGAGATGGAGGATTGCATTGATGATGAGCAGAAAGTAGAAAGGATGTA CCTCT

ACAGAACCTTGGTGGGGCCGAGGAAGGATGCACCAGAGCATGTTTGGACATTGTAGG GTTC

CCCTGAGGTTCATTGCCATGGCTTTGCCTCAAAATCTCCTGTTGTACCATCATTGTA CCTCG

TTTAGGCTCGTAATTTGTGGATTTTTAGTTGTATGGTGATTTTTTATTTTATTCAGA AGAGATT

CTAATGTGCTTCTAGTTATAAATAGATTTTTCTTTAGCAAAAAAAAAA

I ABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

26 GCTCCCTTGTTCCTTATCTCTTCCATTTCCTCAGCCTCTGCTGTTCCTCCACTGGACCTC CCA

CCACCCCCCTCCCTCCTCCCTCCTCCCCCCTAACCCCCCAAGAAAATCAAGAAAATC AAGAA

AAGAGACGCTGCCAGCAAAAGCAGCAGCATGCTAGTCATAAAACCTCCTCCACTCCC TGCT

GCCATGAACGAAATTTGATCCTCAGCTCCCCACTCACAGCCCTCCGAAATCTCTGAA ATCAA

AGCAAGGAAAGAGAGAGAGAAGAGAGAGAAGAGAGAGGGGAAAGAGAGATGAAGAGG GAT

CATCGAGACGCTTGCAGTGGCGGCTATGGCGGCGGCGGTGGCGGGGAGGCGAGCGGC G

CCTCGAAGGGCGAGCCCCCGTCGTCCTCCTCCACCCACTCATTGCCCGGCTCTGGCA AGG

CCAAGATGGTGATGTGGGGCGAGGACGACCAAGATCCGAGCGGCGGTGGCGGGGGCG GC

ATGGACGAGCTCCTCGCGGTGCTCGGGTACAAGGTGAGGTCGTCGGACATGGCCGAG GTG

GCGCAGAAGCTGGAGCAGCTCGAGATGGTGATGGGCTCTGCTCAGGAGGACGGCATC TCG

CACCTGTCCTACGACGCCGTCCACTACAACCCTTCCGATCTCTCCTCGTGGGTCCAG AGCA

TGCTCTTCGAGCTCAACCCCCCTCCGCCGCCGCAGCAGGTGGCCGACGCGGTCCTCG CTG

CGGCCGAGTCGTCTTCCACCATCGCGCAGCACCACCGTTCGCATCTCGGGTCTCGGT CTCA

GACGCAGACTCGGACTCTGAGTCAGACTTCGGCTCCCACTCAGACGCAGTCCCAGGT AATC

TTCAACGACGACTCCGAGTACGACTTGAGGGCGATTCCCGGCGTCGCCGCTTTCCCA CAG

GGCGACTCGGACTTCGAGAGCGCCGCCCGGAAGAAGATGAAGACCCTGAACGGCGGG TC

GAATTCGTTGTCGTCCTCGTCCTCTTCGTCGGCCGCCGGAGCGGCGCCCTCCGAGTC GAC

CCGGCCGGTCGTCCTGGTGGACACGCAGGAGACTGGGGTGCGGCTCGTCCACACGCT CAT

GGCCTGCGCCGAGGCGGTCCAGCAGGAGAACCTGAAGCTGGCCGATGCGCTCGTCAA GC

ACATTGGCCTGCTCGCCGCTTCGCAGAACGGCGCGATGCGCAAGGTAGCGACCTACT TCG

CCGAGGCGCTCGCCCGCCGGATTTACCGAATCTACCCCAACGACGGCAGCCTCGACT CCT

CGTGCAACGACATCCTCCAGATGCACTTCTACGAGACCTGCCCGTACCTCAAATTCG CCCA

CTTCACTGCCAATCAGGCGATTCTTGAAGCCTTCGCCACCGCCAGCCGCGTCCACGT CATC

GATTTCGGCCTCAAGCAGGGTATGCAGTGGCCGGCCCTCATGCAGGCTCTGGCCCTG AGG

CCCGGCGGTCCGCCCGCCTTCCGGCTCACCGGGATTGGCCCGCCGCAGCCGAACAAC AC

CGACGCCTTGCAGCAGGTCGGCTGGAAGCTGGCTCAATTGGCCGACACTATCGGGGT CGA

GTTCGAATTCCGGGGTTTCGTGGCGAATTCGCTGGCTGATCTCGAGCCCGCCATGCT GGAC

ATCCGCCCTCCCGAGGTCGAGACGGTGGCCGTCAACTCGGTGTTTGAGCTCCACCCC CTG

CTCGCCCGACCGGGGGCGATTGACAAGGTTCTCTCATCGATCAAGGCCATGAGACCT AAGA

TAGTGACGATGGTGGAACAGGAGGCGAATCACAATGGCCCGGGGTTCGTGGACCGGT TCA

CGGAAGCTTTGCATTACTACTCCAGCCTGTTCGATTCGCTGGAAGGGTCTGGGGTGG CTCC

CCCGAACCAGGATCTGGTCATGTCCGAGGTCTACTTGGGTCGGCAGATTTGCAATGT TGTG

GCCTGCGAGGGGCCGGATCGAGTGGAGCGGCACGAGACGTTGGTGCAGTGGCAGGCG CG

GATGGGATCGGCTGGGTTCGACCCGGTCCATCTCGGGTCCAACGCGTTCAAGCAGGC GAG

CATGCTGCTGGCCCTGTTCGCAGGTGGAGAAGGTTACCGGGTCGAGGAAAACGATGG TTG

TCTCATGCTCGGTTGGCACACGAGGCCTCTGATCGCCACTTCGGCGTGGCAACTCGC TGCT

GCAACTCAGTGAATCAACTGTCGTTCGGTTGAGTTTGGTCGAAATCGAGATAGACCC TGTTG

TCGGTTGGACCCCTTAGATGATCAGTGAATGGAAGTGCTTTGCCTGAGTTGGGAAGG TACT

AAGAGAAGAGAGGCTACGAAACAACCTCAGAGCGTGTAGTTCCACTTCTTGTTTTTT GCCTC

TGTGTAGTCTTCTGCAAGATCTTCCAAATCTTCCTTATTGATTTATTTCATGAATTT TGATTTT

GGTTAGACCTTTGGGCTCTACTCAAGGTTGGATGAATGCGAATGTGTATCCTCTGCA TTTAG

CTTCTGGAATAAAATGATGACGACGACGATTCTCGCTGCCAAAAAAAAACGGATGCA ATCGT

TTACGATTCATCACATCTCTATGGAACTCCAAGTTACTGGGTGCAACAGTTTTTCGC CGAGT

CAAGTGGAGCMCTCTTCTTGATACAACAATTCCAGCGAATTACTCCAGCTCACTTCT CGCC

TCAGCMTCACGTGGACAMTTCAGATGATGATAAMGTTATATAAAGATTAAGATCGTG MC

TTCGGTAGCAGTCCAGTTAATCTAACAATTTCCATTAGCGGACTGGATCAAMTTCGA TACAA

MGTCTGGATCCTCAMGACGGTATTGACATCTGCTMCTTGMGGATGAGMCTCCTTTTC

TGAGCCGMCMGGTGGTGCCMCCCAAAGTCTACTCGAAMTGCAGGCAMGAGATGGAT

GTTGTTATCTTGCCCTATTCCTTCACTTCCTTTGATCTGTTAAMGMTCGACTAGCAT CCGG

ATGMGGGAGATGATTATTCGTCTAMTCTTCTATCTMTTTATATATCTGATTGAGTGT MTT

ATATGGMTMTCTCATGACTCAGATGTTATGATACTCAAMGTTATGTAGATCTTTGTG GCT

GTMCATGTACTTCTTGCTTACCTGTTCGATGCTATATAATATAAATTATATTACATA AAAAAA

AM

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

27 TTCCTCTCCCCCCACTTCCTTTTTGCCCTATCTGATAGGGTTTCTCACCTTCTTCCCCCC TCC

CTCTCATGCATTCTTGCCCGCTAGCAGCCCTGCAAATCGCCCTGACCTTCTTGATCG TCGTC

TCGGGATCCGCCTTTTTTGCTCTCTCTCGAGGGTTTTCGGGTCGCGACCGTTTCGGA GCCC

GCCTCCCGGAGTCACCGGAGCCGTTCCCATGTCGAAGGTCCTCAGATTCACTGGAGG CGA

GGATTTTTACTCTGGGAGGTCAATATACCAAAGCCCAAAGGAGGTCAACCTCTTTTT GTCCC

TTGGTAACCATGTGGACGTGTATTTTCCTCCTAGCAAGAGGTCCCGCATCAGCGCTC CGTTT

GTTTTCAGTGAGGACCTATTCGAGCAGAAAAGGCAGGACACAATCGAAGTTCTTCCA GATGA

GTGCCTCTTTGAGATATTCAGAAGGTTGCCTGGAGGCCAGGAGAGGAGTGCCTGCGC TTGT

GTCTCCAAACGCTGGCTCAATCTTTTAAGCAATATATGCCCCAATGAACGCAGCTCT GGTAA

ATCTCAGAACAATTTGGATCCTACCTGTGGGGGAGAGGAAGTGAGTTCAGAGGACGA TGGA

TTTCTCTCTAGGAGCTTGGAAGGGAAAAAGGCCACTGATATCCGTCTTGCTGCCATA GCTGT

GGGAACTGCTGATCGTGGGGGATTGGGCAAACTTTCAATCAGGGGTAGCAAGTTGTC CCAT

GTGACAAGCCTTGGTCTTGGGGCAATAGCACGCAGTTGCCCCTCTCTTAAGGCCCTG TCCC

TTTGGCACCTACCTTCTGTCGGAGACGAAGGTTTACTCGAGGTTGCAAATGGTTGTC ACCAG

CTTGAGAAGCTAGATCTTTGCCAGTGTCCCAACATTACCAACAAGTTTTTGGTTGCA GTTGC

AAGGAACTGCCCTAATTTGACCGACATATCAATAGAGTCTTGTTCTAGCATTGGAAA TGAAG

GTTTGGCTGCTGTTGGACAGTTCTGCCAGAATCTGAAGTCCATTTCAATCAAAAATT GCCCC

AGTGTTGGAGATCAGGGCATTGTTGGTCTGATTTCGAGGGCTGGTAGTGCCTTAACA AAGTT

CAAATTGCAGGCATTAAACATAACTGATGTATCTCTTGCGGTCATTGGGCACTATGC CACGG

CTGTTACCGATTTAACCCTTGCGAGCCTCCACAATGTCACAGAGAGAGGGTTTTGGG TCATG

GGCAATGGTCATGGCTTGCAAAGGCTGAGGTCTTTGATAGTCACCGCTTGTCGGGGT GCTA

CTGATCTGGGACTTGAATCTCTGGGGAAAGGTTGCCCTAATCTTAAGCAGTTATGCA TCCGT

TCATCTGCATTCCTGTCAGATGGTGGCCTTGTTTCTTTCATGAAGTCAGCAAGGTCA CTTGA

GAGCCTGCAATTGGAGGAGTGCCACAGGATTACCCTGTCAGGACTATATGGTCTTGT CGTT

GGTTGTGGGGATAAACTGAAATCTCTTGCTCTGACAAATTGCTGGGGATTTAAGGAC TTTGA

TTTTGGATCACCTCAAGTGTCTCCTTGCAAGTCCCTGCGCTCTTTCTCTGTTCGCAA CTGCC

CAGGCTTTGGTGATGCGTGCTTGGTGGCACTTGGGAAGATTTGCCCACATCTGCAGC AAGT

AGAATTGAGTGGGCTTACAGGAATAACGGATGAAGGGCTTTTACGACTGCTTGAATG CTGT

GAAGCTGGTCTTGTGAAGGTTAACCTCAGTGGATGCATCAACCTGACAGATCAAGTG GTTTC

AGCAATGGCTAAGTTGCATGGTAGGACCCTTGAGGTGCTAATTCTGGATGGTTGTAC AAAAG

TTAGTGATCTGGGCTTGCTGGCTATTGCAGAAAATTGCCAACTGCTATCTGATCTCG ATGTC

TCGAAATGTGCAATTTCGGATTTTGGATTGATGGCATTGGCTCGTTCTAGTCAACTG AGTTT

GCAAGTCCTTTCCGTGTCTGGTTGCTCTTTGGTGTCAGACAAGTGCTTGCCTGCTCT TAAGA

AAGTGGGCCGCACCCTTTTAGGTTTAAATCTCCAACATTGCACTGCAATCAGCACTC GTTCG

GTGGACCTGCTTTTGGAAGAGCTTTGGAGGTGTGACATTCTCGCTTGATTGAGAGTG GATG

GAAATTGCAGTTTCGTCTGAAGATTGGATTTATTTGTTATGAAGACTAGAGTTCAAC TCGGCC

TATGTGGACAGCTACAGTTTGTGTTAGTTTTTGGATCCAGAATCCAGCGGATATGGG TGTTG

AAGCAAAATCCGGTGCTTGGTCCTTTTTTCAGGGAATATGGCCTTTCTTTTTTGGCA GGCTT

CCGAATTGGGAATCTGTTCTTAGTAGTTTTGCCTCTCCAAGACGAGAGGAGTCATTT ATGGC

CAGATTTTCCTGAGAATGTCCTGACCAAGTTCCGGTTCAGTTCATCATCAATTTCGA CAGAG

TTTTTATGATGCCTGGGTTGGTATCTGCTGTTTTAGCTCGGCATCATGCTGGTCAAC TATGCT

GGCTTGTGATCAACTTTTCTCCGCGTCTGGATCCTTGCACTTGCAGGAATATTTCGG TTCTG

ACAGGTCTTTCTTGTTCCAGATCCTTGTATGTCATGGGCGGGTCATTCTCCAGAGTT TTGGT

GACGGTCGCGGTTGCTTTTCATGCTTACAATGCCTTGGATTCTTGGGCTTAGGCCAT GGCA

GCTGCTCAAGCAGTCTTGCCATCACAACCCATGAGGTTGTTTTTTTCTAGCCAAGCC TTGTT

TTTCCCGGCATTGCGGTGTGGAAAGTTTCTTCGACCGTTTCGCCACACGTTGTTAGA ATCTC

CCTCCCCCCTGACTATATGTTGGTTTTACAGTTTGTCAAGTGAAATAAAAGCAGTGT ACTTGT

TCATGTTCTAAAAAAAAAA

I ABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

28 GGTAACATTGAGGTCCTCCTCTGCACGTTTCTCCTTCGTCATCGGGGTTCTCTTACCTAG GG

TTTGCAGGCGGGCGCCACTCTTCTCCGCTGTTTCTACCTCTCTCGTTTGGCAGCCAT GGGA

GAATCCAGGAGAGGAGAGATGGATGGAACGACTCGAGGGGGCAGCAATGCGGACATG TAT

CTGCCGAATTATAAGCTCGGGAAGACTCTGGGCATCGGTTCGTTTGGTAAGGTGAAA ATAG

CGGMCACGTGTTGACTGGGCACAAGGTCGCCATAAAGATCCTCAACCGGCGCAAGAT AAA

GAACATGGAGATGGAAGAGAAAGTGAGGAGAGAAATAAAAATCCTCAGACTCTTTAT GCATC

CGCACATCATCCGACTTTATGAAGTCATTGAGACGCCTACGGACATTTATGTTGTGA TGGAG

TATGTGAAGTCTGGGGAGCTGTTTGATTACATTGTCGAGAAGGGCAGGTTGCAGGAG AATG

AAGCTCGCAACTTTTTTCAGCAGATTATTTCCGGTGTGGAATACTGCCATAGGAATA TGGTC

GTTCATAGAGATCTAAAGCCTGAAAACTTGCTGTTGGATTCTAAATGGAATGTGAAG ATCGC

AGATTTCGGTCTGAGCAATATAATGCGTGACGGTCATTTCTTAAAGACAAGTTGTGG GAGCC

CCAACTATGCCGCTCCGGAGGTTATCTCTGGTAAACTTTATGCGGGGCCTGAAGTAG ATGT

ATGGAGCTGTGGAGTTATATTATACGCTCTTCTTTGTGGCACACTCCCTTTCGATGA TGAAAA

CATACCTAACCTTTTCAAGAAAATCAAGGGTGGGATGTACACTCTTCCAAGTCACTT ATCGG

CAGGTTCAAAGGACTTGATCCCAAGGATGCTTATAGTTAATCCAATGAAACGAATCA CCATT

CCAGAGATCCGTCAGCATCCTTGGTTTCAAGCTCATCTTCCACGTTATTTGGCCGTG CCTCC

ACCTGATACGATGCAGCAAGCGAAAAAGATTGACGAGGAAATACTCCAGGAAGTGGT CAAC

ATGGGTTTTGAGCGCAATCAACTTGTCGAATCACTTCGCAACCGGATTCAAAATGAG GCTAC

TGTTGCATACTACTTGTTATTGGATAACCGTTTCCGACCTTCCAATGGCTACCTCGG AGACG

AGTTTCAAGAAACGATGGAGTGCACCTTCAATCGTGGAAATCCAGGGGAGCTTACCA TTCCA

ACTGTTGGGCCTCGCTACCCACTACCTGGATATATGGATTACCAGGGAGTGAATTCA AAACC

AGGTTATTATGGTGCTGAGAAGAAATGGGCTCTTGGTCTCCAGTCTCGAGCCCATCC ACGG

GAAATAATGACTGAAGTTCTTAAGGCGCTGCGAGAACTAAATGTGTGCTGGAAGAAG ATTGG

GCACTATAACATGAAGTGCATGTGGAATCCTTGTGTTCCCAGTCATGAGAGCATGGT TAGCA

ATCCTGTCCAGAGTAATTATTTTGGTGATGAATCTACAATAATCGAGAATGATGGCG CAACC

AAGTCCAGAAATGTGGTCAAGTTTGAGGTGCAGCTTTACAAAACGACGGAGGAGAAA TATTT

ACTCGATTTGCAGAGGGTGCAGGGACCCCAGTTTCTGTTTTTGGACCTCTGTGCTGC TTTTC

TTGCCCAACTCCGGGTCCTTTAGGAAGAGAAGGGTGAAGATATCCACGAAAAGTCCT GCCA

ATAAAACTTGTGAATAACCATTGGAGGATTTTAGGCGTTCAACATTCATCAGGAAAT TGATAT

CAAGCTTTTTGTTCTATATCAAAAATAAAACGTTAAAGAAAAACTCGTGGAAAATAC AGTTTTG

TACCAACTGACGAGGTCGTTTCAGATGTTGTGTACTTAATCGAAAGTGATCTTTATT TACACT

TAAAAAAAAAA

29 GAAGGGGGGCTCTCTGTTTTTTTTAACGAGGAAGGAAACAAGCACGTCGTGCAACTTGCC G

TGTAGCTCTCGAAAACGCCCCTCCTTCTCTCTTTCTCTCTCTTCTCTCTCTTCTCTC TTTCTC

CTGGGTCTGAGCAAGAAATGGCAGGGTACAGAGCAGAGGATGACTACGACTACCTCT TCAA

AATTGTCCTGATTGGGGACTCTGGCGTGGGCAAGTCCAACCTGCTCTCCAGATTCAC CAGG

AACGAGTTCAGCCTCGAGTCGAAGTCCACCATTGGGGTCGAGTTCGCCACTCGGAGC TTGA

ACGTCGATGGCAAGGTCATCAAGGCCCAGATTTGGGACACCGCTGGTCAAGAAAGGT ACC

GTGCCATCACTAGTGCTTATTACCGGGGAGCTGTGGGCGCATTACTTGTGTACGACG TTAC

TCGTCACTCCACATTCGAAAACGTGGAGAGATGGTTGAGGGAATTGAGGGATCACAC GGAC

CCCAACATCGTGGTCATGCTCGTCGGCAACAAGTCCGATCTCCGGCACCTCCTGGCA GTCT

CAACAGAGGATGGGAAATCATTTGCGGAGAGAGAGGCCCTCGTCTTCATGGAAACTT CTGC

ACTCGAGGCGACCAACGTGGAGAATGCTTTCGCCGAAGTCTTGACTCAGATTTACAA CATC

GTGAGCAAGAAGGCCCTGGAAACAAGTGAGCAAGCAAATGGCTCGGCTGTGCCGTCT CAG

GGAGAGAAGATTGATGTTGGTAAGGATGTGTCAGCTGTCAAGAGAGGTGGATGCTGC TCAA

GCTAGTCAGATTCTTGGAACATTCGAGAGTTTTGGATTACTGGGTAGTTGCCGTTTT TCCTG

TCATCATATTTTGCGATATATAGCGTGAGATATTTTTTCTGCACGACACTGGCCGAT CCGGTC

TAGATTGCAGGTACACGAATTTGTATCATTTATGTCAGCGATTTCTTGTGATGGGTA CAGAG

CTTAATTTAGGAAACTGCTTGTTAATTTTACATCTATTGGTTCATTACCATGTTGGT CTTCTTT

TGTTTTTAGGACACAATGTATTAGGTGCTTGATGCTAGCGCGGACACATTGTATTAT TTTCCG

AGGGAATCATGACGTTGAATTGGAAAAAAAAAA

I AbLt 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

30 CCAAGCTGTCTTCATCATTTCTCGCTGGGAATCMTTTGMTTCGATTCGATTTCGCCGTGT C

GATCGAGGATCGCTCGATCGATCGATCGATCAGMTCCCCAGTTCGTCTGMTCCTTCT CTC

CCTCCCTCCCTCTCTCTCTCTCTGTGTCTCTCTCTCGCCATTTCCGTGAGATCCAGC TATGG

ACTCCTCTCGCGAGAGCCTGGTCTACGTCGCGMGCTCGCGGAGCMGCCGAGCGCTAC G

AGGAGATGGTGGATGAAATGMGAAGGTTGCGMGCTCMTGTTGCATTMCCGTTGMGA

GAGAMCCTGCTATCTGTTGGGTACAAAMTGTTATTGGGGCTCGGAGAGCATCCTGGA GG

ATTCTGACATCCATAGAGCAAAAGGAAGATGCMGGGGGMCGAGATCAGTGTGAAGCG M

TCMAGAGTACAGGMGMGGTTGMTCAGAGCTCTCTAGCATCTGCAGCGATATCATGGT C

ATACTTGATGAGCATGTCATTCCTTCAGCATCAGACGGTGMTCCMAGTATTTTACTA TMG

ATGMGGGAGACTACTACCGTTATCTTGCGGAATTCMGAGTGATGACGAGMGAMGAGG

TTGCTGMCAGTCAATGAAAGCTTATGAGATGGCTACMGTATTGCAGAGTCCGATTTG CCT

TATACACATCCCATCCGCCTTGGTTTGGCTTTGMTTTTTCGGTGTTTTACTATGAGA TCCTC

MCTCAGCTGAAAGGGCATGCCACATCGCAMGCAGGCATTTGATGATGCAATTGCAGM C

TTGACMCCTCMTGAGGAGTCTTACAMGATAGCACTTTMTCATGCMCTTCTCAGGGAC

MTCTCACATTGTGGACATCTGACATCACAGAGGAAGGAGMGATGCACAMGGATAAAT G

GCTCAGCTAMGTTGGCATGGAAGMGGAGAGTAAAACAGGTGTMCCCTGAATCATATG C

CTTGCAGTGGGTCGACGCGGCCGCG

31 CGTTTCCGCGCTTCTGCTCGCGCGTCCTCTCGCTCGAGGCTTTCCGCTTCCTTCTTCCGA A

CCCCTTAMGGTCGGGTCTTTCCCTCCCCCCTCTCGATGGATCCGGCCGCCGGCTCCG GC

TCCGGCTCCGGGCTGATCCGATTAGGGTTCTTGGCCGGCTCCGACGAGTGAGCTGTC GCC

CGCCTCCTCGCGGGCGGTTTTCCGGCGGCGGGTTTAGGGTTTTGCCCTTTTTCCGTT CTTG

AGAGAGAGAGAGAGATAGATAGAGAGAGAGAGGGGGGGGAGGTGATGGAGGATCGGM C

GTGAAGAGGCCGGACAGCCCGGGGCTTTCCGACATCGTGTTGACCTGCGTCATGCCG TAC

ATCGACGACCCCMGGATCGGGACGCGATTTCCCTGGTCTGCCGCCGCTGGTACGAGA TT

GACGCCCTCACGAGGAAGCACGTCACCATCGCCCTCTGCTACACCACCAGCCCCGAA CGG

CTGCGCAGGAGGTTCAGGCACCTCGAGTCGCTCMGCTCMGGGGMGCCGAGGGCCGC

CATGTTCMTCTGATACCCGAGAATTGGGGCGGGTACGTGACTCCCTGGGTGACCGAG ATC

GCGCAGTCTTTCGATTGCTTGAAGTCGCTTCACTTTCGGCGCATGATCGTGGMGATT CGAA

CTTGGAGGTGCTCGCCACGTCGCGGGGACGCGTTCTGCMGTGCTCAAACTCGACMGT G

CTCTGGTTTCTCGACCGACGGGCTTTTACACGTGGGGCGTTTATGCMGACTTTMGMC CT

TCTTTTTGGMGAAAGCACMTCATTGAGAMGATGGTGCGTGGCTTCACGAGCTTGCTA TG

MCMCACAGTCCTTGAGACTTTAMTTTTTACATGACAGAGCTATCCAGTTTTAGTGTC CAG

GACCTTCAMTTATTGCCAGAMTTGTCGATCGTTMCATCTGTGAAMTTAGCGATTGCG M

ATTCTGGATCTTGTGGGTTTCTTTCMGATGCAGCTGCTTTAGMGMTTTGGTGGAGGT CT

TTTTAATGAGGMCCAGAAAGGTATGCTGCTTTATCGTTCCCAGCMGATTATGCCGTT TGG

GTCTMCCTACATTTCAGAGMTGAGATGCCTATCGTGTTCCCTATTGCATCTCGGCTA AGG

ATGTTAGATCTTCTCTATGCATTTCTTAGCACAGATGACCTCTGCTTGCTGATTCAG CMTGC

CCCATCTTGGMGTTCTTGAGACAAGGAATGTCATTGGAGACAGAGGATTAGAGGTTC TTGC

TCATAGTTGTAAMGGTTGMGAGGCTTAGGATTGAMGAGGTGCTGATGAGCAGGGTAT G

GGGGATGMGGAGGCCTTGTTTCGCAMGAGGATTMTGGACTTGGCTCGGGGCTGCCTA

GMCTGGMTACCTGGCTGTTTATGTATCTGATATCACAMCTCATCCCTCGAATGTATA GGA

ACTTATTCGMGMCCTTTGTGATTTCCGTCTTGTTCTACTTGACCGCGAGGAAMGATM CT

GATTTACCCCTGGACMTGGTGTCAGGGCTATTTTMGGGGATGTGAMAGCTMGMGGTT

TGCTCTTTATCTGCGGCCTGGGGGCTTGACAGATGTGGGTCTTGGTTACATTGGGCA GTAT

AGCCAAAACATMGATGGATGCTTCTTGGATATGTGGGAGAGAGTGATGAGGGCCTTA GGG

AGTTCTCCCGAGGCTGCCCGAGTTTGCAMMCTTGMATGCGGGGTTGTTGCTTTAGCG A

ACAGGCGCTGGCTGATGCTGTGATGCGGTTGACTTCTTTGAGGTATGTCTGGGTGCA GGGG

TATAGAGGATCTGACACCGGTCGAGATATTCTGGCGATGGTCCGTCCCTTTTGGMCA TCG

AGTTGATTCCTGCTAGMGMTAGCTGTTGCCMTCAGAATGGGGAAMCGTGCTTMTGM

GACCCAGCCCATATACTTGCATATTACTCTCTAGCAGGACCMGMATGATTGTCCTGA CAG

CGTTATACCTTTGGCTCCAGCMGGCTGCTTACCTTGTAGAGCTGTATATACACCCTT TTGC

CGAAGATGTCTTTTATCTTCTTMGTGCTCTAGACCCCCTGTCATACGGTTCTGTATT TTATC

ACTCCTCCCTGAGAMTTTCTCCTCTTGCTTTACTTTTCGTCTTCCGTTTGTTGGMTT CCTTC

TTTTCTCTTTTATTTTGTCGCMTMGATTGTGTACTTTGTAAAAAAAAAAAAAAAAAA

I ABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

32 AGGTTTGGGTTTTTTTTTTTTTTTTAGGGGCGATCGGGGGATGGCGAACCGGGTGGATGA C

GAGTACGATTACCTGTTCAAGATCGTCTTGATCGGGGACTCCGGCGTCGGCAAATCG AACA

TCCTCTCGAGGTTCACGAGGAACGAGTTCTGCCTGGAATCTAAGTCCACCATCGGCG TTGA

GTTCGCGACGAGAACCCTGCAGGTTGAGGGAAAGACCGTCAAGGCACAAATATGGGA TACT

GCTGGTCAAGAGCGATATCGAGCCATTACCAGTGCATACTACAGGGGAGCAGTGGGC GCTT

TGCTAGTTTATGACATAACAAAGAGGCAAACCTTTGACAATGTCCAGAGGTGGCTTC GGGAG

CTGAGGGACCATGCAGATTCTAACATAGTTATTATGATGGCTGGGAACAAGTCTGAT TTGAA

CCACCTAAGAGCTGTCCCGGGGGACGATGGTCAAGCCCTGGCTGAGAAGGAGGGTCT TTC

ATTTCTTGAGACTTCAGCATTGGACGCAACAAACATTGAGAAGGCGTTTCAGACAAT TTTGA

CAGAGATCTACCACATCATAAGCAAAAAGGCATTGGCAGCTCAGGAAGCTGCTGCTA CTAC

GCTTCCTGGTCAAGGGACCACAATTAATGTCGCTGATGCCACAGGGAATGCCAACAA GAGA

GGCTGTTGTTCTACTTAAGGCGACACTGTGATTCAGGAGACAAAATTTGAGTGGTAA TTAAC

CCCAGCAGCTTAGATATGAGCCCATTTTCTTTTGGGTCAACGAGACATTTGTAGAAT ATTTGT

GGTGTTCTTTTCCTCCCCCGTTTTATTTTTCTTTTTACTC

33 GCCTCGTGCCGAATGCAAGGCAAACAAGCAAGTGCATTATCTTCGTTCTGAGTGAGAGAG A

GAGAGAGAGAGACCAAAAGACAAGCAAGGTTTCACTACAGCTTCTAGAGAGAGAAAA TGGA

GAGCTTCCCAGTGATCAACATGGAGAACTTGAATGGTGAGAAGAGAGCAATCACCAT GGAC

AAGATCAAAGATGCTTGTGAGAACTGGGGCTTCTTTGAGCTGGTGAATCATGGGATT CCACC

CGAGTTTATGGACACGATCGAAAGCATGACAAAGGGGCACTACAAGAAGTGCATGGA GCAG

AGGTTCGGAGAGCTGGTGGCGAGCAAGGGGCTCGAGTGTGTCCAGACAGAGGTCCAC GAC

TTGGACTGGGAAAGCACCTTCCACTTGAAGCACCTTCCTGTCTCTAACATCTCCCAA ATCCC

AGATCTCGATGATGACTACAGGAGAGTCATGAAGGAGTTTGCACTGAAATTGGAGAA GCTG

GCGGAGGAGCTCATGGACCTACTGTGTGAGAACCTGGGCCTGGAGAAAGGCTACTTG AAG

AAGGCCTTCTACGGGTCCCMGGACCGAACTTCGGCACCAAGGTTAGCAACTACCCGC CGT

GCCCGAAGCCCGACCTGATCAAGGGGCTCCGGGCCCACACCGACGCCGGTGGCATCA TC

CTGCTCTTCCAAGACGACAAGGTTAGCGGCCTGCAGCTCCTCAAGGATGGCCAGTGG GTTG

ACGTCCCCCCAATGCGCCATTCCATCGTCGTCAACCTCGGAGACCAAATCGAGGTGA TAAC

TAATGGAAAGTACAAGAGCATACTGCACAGGGTGGTGGCCCAGACCGATGGAAACAG GATG

TCCATAGCTTCATTCTACAACCCAGGCAGCGACGCCGTGATCTATCCGGCACCGGCA CTTG

TGGAGAGCGAGGCAGAGGAGGCCAGCAAAGCAGTTTACCCAAAGTTCGTGTTCGAGG ACT

ACATGAAATTGTATGCTGCTCTCAAGTTCCAAGCCAAAGAGCCAAGGTTCCAAGCCA TGAAA

GCCATGGAGTCGAGCCCCAGTTTGGGCCCAATCGCAACCGCTTGATTTGGAGAATTT AGGA

CTTCTCTAAGTGTGGACGCAGAAGAATAAATTGGCTTTTTTTTTATTATTATTTTTA GGTTATG

ATTGGACCAACTGAGGAGATTCTATCCATCAGTTTAAGTACATATTTGAACTCTGTC CCAATA

TGTACTTTGATTTATGGATTGTAACGATGTACTCAATTGGAAATAATAGGAGCGAAA GATCAT

TTAAAATAAAAAAAAAAAAAAAAAAAAA

34 GAGAGAGAGAGAGAGAGAGAGAGAGAGAGACCAAAAGAGAAACAAGGTTTCACTGCAATT T

CTCAAGAGAGAAAATGGAGAGCTTCCCAGTGATCAACATGGAGAACCTGAATGGTGA GAAG

AGAGCAATCACCATGGACAAGATCAAAGATGCCTGTGAGAACTGGGGCTTCTTTGAG CTTG

TGAATCATGGGATTCCGCCCGAGTTCATGGACACGGTCGAGAGAATGACCAAGGGGC ACTA

CAGGAAGTGCATGGACCAGAGGTTCAGAGAGCTGGTGGCGAGCAAGGGGCTCGAGAA TGT

CCAGACGGAGGTCCATGACTTGGACTGGGAAAGCACCTTCCACTTGAAGCACCTCCC CCTA

TCCAACATCTCCCAAGTCCCTGATCTCGAAGATGACTACAGGAAAGTCATGAAGGAG TTTGC

AGTGAAGTTGGAGAAGCTAGCGGAGGAGCTCATGGACTTGCTGTGTGAGAACCTGGG CCT

GGAGAAAGGTTACTTGAAGAAGGCCTTCCACGGGTCCAACGGGCCGAACTTCGGCAC CAA

GGTCAGCAACTACCCGCCGTGCCCCAAGCCCGAACTGATCAAGGGGCTTCGGGCCCA CAC

CGACGCTGGCGGCGTCATCCTGCTCTTCCAGGATGACAAGGTCAGCGGCCTACAGCT CCT

CAAGGACGGCCAGTGGGTTGACGTCCCCCCGATGCGCCACTCCATCGTAGTCAACCT CGG

CGACCAAATCGAGGTGATAACCAATGGGAAGTACAAGAGCGTGCTGCATAGGGTGGT GGC

CCAAACTGACGGGAACAGGATGTCCATAGCTTCATTTTACAACCCGGGCAGCGACGC CGCG

ATATATCCAGCACCGGCACTCATGGAGAGCAAGGCAGAGGAGGCCAGCAAAGCAGCT TATC

CAAAGTTTGTGTTCGAGGACTACATGAAACTGTATGCTGCCCTCAAGTTCCAGGCCA AAGAG

CCAAGATTCCAAGCCATGAAAGTCATGGAGTCGAGCCCCAATTTGGAGCCTATTGCA ACCG

CTTGATTTGGGAAATTCTTTTTCGCAATTCTTTGCTTGCAAAAGATGTAGTCATACA CATTATG

GAAGTCCTCTAGGGTTAGAAAGGACTCTGAATTTTTTGGTGGTGGAAGGAAATTTTT TCCTA

CCCCAAACTTGATAAAAATTGTCATTGTGACTCATGTTAGTATTTGACATGATTCGT GTTAAAT

TATTTATGAAATATTGCATGTTATAGTCAAAAAAAAAAAAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

35 GCGAGGACATCATCACCAACGCCGCCATCGAAGAAGGGGCGAATCTGAAGCGAAAGAAGA

GATGAGCGGCGGCAGCGACCTCCCTGAAGAGATCCTGATCCAGATCCTCCTGAAATT GCCC

GTCAAGTCACTTGTACGATTCCGATGCGTCTCCAAGTCGTGGGACTCCCTCATCACC CACC

CATCCTTCGTCTCCCTCCACCTCCGCCACGCCATGGCGGGCCACGACCGCTCCGTCA TCCT

CCTCCGGCACTACTCCCTCACCCAGCGCAAGGAGCGGAACACCCTCTACCTCGACGG GGA

GTCTTTCTTGGAGCACCAGGAGCTCGAATTCCCCTTGAAGACCCACGACACTTACTA CCTCG

CCGGCTCCTGTAATGGGTTGCTCTGCTTTTCCGACTATATCATCAACAACCTCCAGG TAATC

CTCTGGAACCCTTCCCTCAGGAAGTGCGTGCAGTTGCCGATCCCGCGGTTCATTGAT ACTG

ATCTCACGCACACGTATGTTCTCGGGTTTGGGTTCGATACGCGGCGTGTCGATTACA AGGT

CGTGAGGTTGATTTACATTCTGGGGAAGAATTGGTCCGTGATAGTGCCACCGGAGGT TGAG

ATCTATGAGCTTAAAACTAATGCTTGGAGAGGGATCCAGACGGCCGTTCCTTATGTC ATACC

AGAATCTTCGTCGCAGGCCTTTGTGAATGGGGCTATCCATTGGATTGGGTATAACCC AGCT

GATAGGCGATTGAAGGTGGCTTCAAGTCCTAGGTCGATTGTGGTATTATTCGATATG CAGGA

CGAGGTGTTTGGGGAAATGGAGTTGCCGAAAGGTGGGGATTATGCGAACAGGCTGAA TTTG

TCGCTGGCTGTGCATCAAGATTTGATTTGCTTGTTGCATTGCCATCCGATGGAAGAA GATGG

GCATCAGTTGTATGGGGTTTGTTGGGTCTGGGTCATGAAAGAATACGGCGCAGCAGA CTCC

TGGACTAAGCTGTTTACCATTAACATCAGTGAACACGGCGGGATCGGGAGGATTTTA GGTTT

TAGGAAAAAGGGGGACGCTCTGCTCGTGACTCACAATGACGAGCTGGTTTCATATGA CTTG

AGGGGTCAGAGAATTAGTCGGCTTGGATTGTATGGTGTTGCGAGATCTTTTGAAGTC ATCCC

ATACATGGATTGTCTAATTTTAGTGTGAGGAGAGCACACACTCTCCAGACAACCATA TTTCAT

GGCTGGTTAGGTTGTAGGTAGATTATGTTGGATTTCGCTCTCCTGAAGGAGTGAAGC ATATG

ACACAAATAATGGAGAACCAGAGTGATTAGAGATACTTAGACTTTAGTTGTTGTATA CGGGTT

GATTGCTGTTTTCTCTAGAAGTTATTCTGGACTAGTGAAGTATGTCCTTTTACTTAT CTGAAT

GATTTTTTATTTTTTGGGAGTTTCAGATGGTTGATTGGATGTATGCTACTGAAAGTT GGGGCT

TCTATTGCTACTGCCAGTTGCCCTAGCAGAAGAATGATAATAATTTCTTTGTTCCAA AAAAAA

AA

36 CCCGTAGCGTCGACCACGCCAACTACCTTTCATTCGTGCCCGTCGATACTCCAACGAACT C

CAGTCCTCCTCCCCCTCTCCGTCTCGGTCGCGCTCCCCGCACGCCGACCTTCGATTT CGAC

CAGCGGTTCTCTCGAGCTCCCGCGCGTCCGCCGATCCGAGCGTCCGCCGGATTCACC TCG

TCGGAGCCGCCATGGGTTGCTCCTCTTCGCTTCCAGATAGGGCTTCTGGGAGATTGG GCG

GGCTCAATTCGGAGAACGGTGCAGTGAACGACGCGAAGAACCTGCGTGTTAAGCTTG TACT

TCTAGGGGATTCTGGTGTTGGGAAAAGTTGCATTGTACTTCGCTTTGTCCGTGGTCA GTTTG

ATCCGACATCTAAGGTGACTATTGGAGCATCGTTCCTGTCACAGACCATAGCTTTGC AAGAT

TCTACGACAGTTAAGTTTGAAATATGGGACACTGCTGGTCAAGAGAGGTATGCTGCC CTGG

CCCCACTTTACTATCGGGGTGCTGCGGTTGCGGTAGTGGTTTATGATATAACAAGCC CGGA

ATCATTTCAAAAAGCTCAGTACTGGGTCAAGGAGCTTCAAAAACATGGAAGCCCTGA TATGG

TTATGGCTCTGGTTGGAAATAAAGCTGACCTTCAGGAGAATAGAGAAGTGACGGTCC AAGAT

GGGATTGACTATGCTGAGAAGAACGGCATGTTTTTCATTGAGACATCTGCTAAAACT GCAGA

TAATATAAATCAGCTGTTTGAGGAAATTGCCAAGCGACTTCCACGTCCAACACCGTC ATGAT

TGGGAAGTTCATACCGTGTTTAAAGCCGCAGATGATGTTATTGGAGTCTTCAACGGC GGTGA

TGTAAAATATCTATCCCAATGTATACCTCCTGTCCTGGAATTCTTTGGTCGACAGTT ACTTTC

ATTTGTCCATGAATTCACTCCACATAAGTTGTAAGATGATCAATCCTCAATTGTACC AGAGAG

AGCTTGCGAAAAAAAAAA

I ABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

37 GCAGCAGCAGGCGCAGCAGAAAGGAAACAAAAACAGGGAGGAAAGGAAAACGACCTTTCC

CACTCAAAAGCTCCTCCCTTTTTCATTTGCATTTCTGCATCCACACAGGCACAGGGA GACAA

GGGGACCGAGTCAGTGAGTCGGAACGGTTGACCGCGGAATCTCCCCCCCCCAACAAA AAG

CCATCGCCCAACTCAGGCCAACAGTCAAAACCCACCTTAACCGAATTCCCCCAGATC AATCC

CCTCTCTCTCTCTCCTCCACTGTAACGGAATCGCGACCCCCAAATCCTAGGGCTTTC TTTCT

CTCTCTTTCTCTCTCTATTTCTACCACCACCATCACCACCACCGATGGACGGCGGGG CTCCT

CAGCCGGCGGATACCGTCATGTCGGAGGCGGCGCCGGCGCAGCAGCAGCAGCAGCAG CC

GCAGCAGGCGCAGCCGCAGGGGATCGAGAACATCCCAGCGACGCTCAGCCACGGGGG CC

GCTTCATCCAGTACAACATCTTCGGCAACATCTTCGAGGTCACCGCCAAGTACAAGC CCCC

CATCATGCCCATCGGCAAGGGCGCCTACGGCATCGTATGCTCGGCTTTGAATTCGGA GACG

AACGAGCACGTGGCCATAAAGAAGATTGCTAATGCTTTCGATAACAAGATCGATGCG AAGA

GGACTCTCCGTGAGATCAAGCTTCTCCGGCACATGGACCATGAAAACGTTGTGGCAA TTAG

GGATATCATTCCACCGCCACAGAGAGAGGTGTTCAATGATGTTTATATTGCATATGA GCTTA

TGGACACTGATCTGCATCAAATTATTCGTTCCAACCAAGCATTGTCTGAGGAGCATT GTCAG

TATTTTCTATATCAGATCTTGCGAGGATTAAAATACATACATTCTGCAAATGTTCTG CATAGA

GACTTGAAGCCCAGCAATCTTCTCCTAAATGCAAATTGCGATTTGAAAATATGTGAT TTTGGA

CTAGCTCGTGTCACTTCTGAAACTGATTTTATGACAGAATATGTTGTCACAAGATGG TACCGT

GCACCAGAGCTATTGTTAAATTCTTCAGACTATACGGCGGCAATAGATGTATGGTCT GTAGG

CTGTATCTTTATGGAACTAATGGATCGGAAACCCTTGTTTCCTGGCAGAGACCATGT GCAAC

AGCTGCGTTTGTTGATGGAGCTGATTGGCACCCCATCAGAGGCAGAGTTGGGGTTCT TAAA

TGAAAATGCTAAGAAGTATATCAGACAGCTTCCTCTGTACCGTCGGCAATCTTTCAC TGAAA

AGTTTCCCCATGTCCACCCACTTGCAATCGATCTCGTTGAGAAGATGTTAACGTTCG ATCCC

AGGCTGAGGCTCACAGTTGAAGAGGCATTGGCTCATCCCTACCTAAACTCACTGCAC GACA

TCAGCGATGAGCCGACTTGCATGAATCCATTCAACTTCGACTTTGAGCAGCATGCAC TCACG

GAGGAACAGATGAGGGAGTTAATTTATAGGGAAGCGCTTGCATTTAATCCCGAGTAT CTACA

GTAATGGAAGTCATGCTGTTAGTATTTGGTGGCTGTTCTCGAGTGTGATGCCCGCGC TTTAA

CATGGCGATGATTTATTTCTTCATGTACATATGGTTTATCCTATTGTTGGATGGCTC TGCTAT

TGAATTCTTTTCATGACTTCGAGAACCATAAGAATTTTCAAAAAAAAAA

38 TTCCCTCTTCCTCTTCCCTTCCGTTTCGAGCTCGCTCCATCTCCTCCGACGAAAGATCCG AG

CCCCCTCCTCCTCCCCCAGCACCATCCGGGCCCGATTCGGGTCGGGTCGGGTCGTCC GGA

GCGGACCCTCTCCTCCGCGCTCTCCTCCGATGGAGTCGTCGAGCTCGGGAGGTGCCT CGG

CGGAGCACAGCGTCCGCGGGATCCCCACGCACGGCGGGCGCTACGTGCAGTACAATG TGT

ACGGGAACCTCTTCGAGGTCTCCAGGAAGTACGTCCCCCCGATCCGCCCCATCGGCC GCG

GCGCCTACGGTCTCGTCTGCGCTGCCATGAATTCAGAGACAAATGAGGAGGTTGCCA TCAA

GAAGATTGGCAATGCGTTTGACAACAGAATAGATGCCAAGAGGACTTTACGAGAAAT TAAGC

TTTTATGTCATATGGATCATGAGAATGTTATTGGCCTTAAAGACATTATACGTCCAC CAAGTA

GGGAGAACTTTAATGATGTTTACATTGTGTATGAATTGATGGACACTGATCTCCATC AAATTA

TCCGTTCCAATCAGCCATTGACTGACGATCACTGCAGGTACTTCTTGTATCAGTTGC TTCGA

GGTCTCAAATATGTGCATTCAGCAAGTGTTCTGCATCGCGATCTGAAGCCAAGCAAC TTGTT

TCTGAATTCGAATTGTGACCTTAAAATTGGAGACTTTGGGCTAGCTAGGACCACATC TGAAA

CGGATTTTATGACTGAGTATGTAGTTACTCGCTGGTATCGTGCACCAGAACTGCTCC TTAAT

TGTTCAGAGTACACTGCTGCGATTGATATTTGGTCTGTGGGTTGCATACTTGGTGAA ATTAT

GACTAGGCAGCCCCTATTTCCAGGCAAAGACTATGTCCATCAGCTGAGACTTATTAC AGAGC

TTATAGGATCTCCTGATGACTCCAGCCTTGGGTTTTTAAGAAGTGATAATGCACGAA GATAT

GTAAGACAGCTTCCACAGTACCCAAGACAGCAATTTTCTAGTAGATTTCAGACTATG TCTCC

AGGTGCTGTTGATCTCCTAGAAAGGATGCTCGTCTTTGATCCCATCAGGCGAATAAC AGTTG

AGGAGGCTTTGTGCCACCCTTATTTGGCCCCTCTACATGATATAAATGAGGAACCCA TTTGC

CCGACTCCCTTCATTTATGACTTTGAGCAACCGTCATTTACTGAAGAAAACATTAAG GAGCTC

ATTTGGAGGGAGACTCTGAGATTCAATCCAGATCCCATGCATTAGGGATTTGCGACA GGTTG

TCGCTTTGTTTAGTAATGTTCTACACTTAACTGGTTGGATGTTTCATTCAAAAAATG AAACAA

GTGTGCTGTAGATAGCGAAATTAGTTTTGAAGTTTTCTACACAGCTGGACAAAAGTT CTTTGA

GCTTGGATGCTATGTATGCTTGTAATGTTCAACTTGTTCAGCCGATGATAAAAGGTC TTCACT

CTTGAGGCTTAAAAAAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ IO NO Sequence

39 GCCCAAGTTCGCATCTTTCGTCCTTTCCCCACGTACCCATTTGCTCATTCCGCCGGAATT CG

GCCGGAATTCCTCCCCCGCCGCCGCAATGGGGCAGGTCCCGTCTTCCGCCTCCTCCT CCC

CCGAGCCCAGCCACCGCGGCGGCGCGATCTCGTCCAGCCACCGCCTCGACTCCCTCC CCT

CCCTCGAGTTCGTCTCGTCGTTCGAGGACGAGGAGGACGCCGCCGCCGCCGACGAGG GG

GCCGCCGCTGGGTACGACTACACCGGCGACCTCCCCGACGAGTGCCTCGCCCACGTT TTC

CACTTCCTCGGCACCGGCGACCGGAAGCGGTGCTCCGTCGTGTGCCGGCGGTGGCGC CG

CGTCGACGGGGAGAGCCGGCACCGGCTCTCGCTGAACGCGCAGGCCGACCTGCTCTC GT

CGCTCCCCTCCGTGTTCTCCCGCTTCGACGCCGTCACGAAGCTCGCGCTCCGGTGCG ACC

GGAAGTCGGTCAGCCTGGGCGACGAGGCGCTGGTCCTGATCTCCCTCCGGTGCCGCG GC

CTCGCCCGGCTCAAGCTCCGCGGCTGCCGCGAGGTCACCGATCTCGGGGTCGCGGCC TT

CGCCGAGAACTGCCGGCAGCTGAGGAAGCTCTCCTGCGGGTCGTGCTCGTTCGGCGC GA

GGGCCATCAATGCGGTGCTCGACCACTGCGTGAATCTGGAGGAGCTGTCCATCAAGC GCC

TCCGGGGAATCCACGACGGCGCCGAGCCCATCGGGCCGGGAGCCGCGGCGAAGTCGC TG

AGATCCATTTGCTTGAAGGAGCTCATCAATGGTCAGTGCTTCGGTCCTCTCCTGGTC GGAG

CGAGAAAGCTCTCGACTTTGAAGTTGATTCGCTGTCTGGGCGATTGGGACAATGTTC TCCA

GACAATTGGGAGCTCAAATCCAGGTCTATTAGAAGTTCATTTGGAGAGAATTCAGGT GAGCG

ATGGCGGTCTTTGCGGGATCGCGAACTGCAAGGGTATCGACAGTCTGCATGTCGTGA AGGT

CCCCGAGTGTTCGAATTTAGGTCTTTCTAGCATTGCTGAGAATTGCAGGCAATTGAG GAAGC

TTCACATTGATGGGTGGAGGATAAACAGGATAGGCGACGAGGGTCTGGTCGAGGTCG CCA

AGCAGTGCCTCCAGTTGCAGGAGCTGGTCCTGATCGGCGTCAGCGTGACCCATTCTA GCTT

GGCCGCAATCGGTTCCAATTGCAGGAAATTGGAAAGGTTAGCCTTCTGTGGGAGTGA CACG

GTCGGTGATGCGGAGATTGCGTGCATTGCCGCCAAGTGCGAGGCCCTGAAGAAGCTC TGC

ATTAAGAATTGCCCCATTACTGATGTCGGGATCGAATCCCTTGCTCAGGGGTGTCCC AATCT

GGTGAAGATTAAGGTGAGGAAGTGCAGGGGAGTGAGCGGGCAAGTGGTGGAGCTGTT GAA

GGAGCGGAGAGGGTCGCTGGTCTTCAATTTGGATGCCTGTGGAATCGAAGCATTGGA CGAT

ATCAGAGGAGTTCAAGAAAGTGTTATGGAGTTCCCTCCTGTGAATACTTCCGATGCG CCGTC

GAGTAGCAATGAGAGGTCAATGTTGTTTAGGGCGAAGCTAGGTCTTTTCGCGGGTAG GAAT

TTAGTGGCCTGCACCTTCAGGAGGTGGTCAAATGGTGAACATAGCACCAATGGAAAC TTGT

GAATTCCAATTGTTGTAAGCGCTGAAAATTGTTTTGTTGACATTTCGTTGTGTTTAG ACCTTC

CCTAGGCAATTCTTGTTCGCAATGATGTACCTATTATCGCCCTTTTGCCTCGTGCAA CTTTTC

TTGGAAATGAAACTCGAGTTCTTTTAAAAAAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

40 GGCTCCAAAACAACCAAATAACTCACACTGAGCTCTTCCTCCTCCTCCTCCTCCTCCGCC TC

TATATGGCCGTCCAGATCTAAACACCACTTCTGCCCTTCTCTCTCTCTCTCTCTCTC TTGCCT

TTCCCTCGGAGCCAATCAAGAAGAAGCTAGAGCTCCGGTCCTCGCTCCCGAGATTCA TGGC

GTACTCGTTCCCGGAGGAGGTGCTGGAGCACGTGTTCTCCTTCATCGGCTCCGACCG GGA

CCGCAATGCCGTCTCCCTGGTGTGCAAGTCGTGGTACGAGATCGAGCGCTGGTGCCG GCG

GCGCGTCTTCGTCGGCAACTGCTACGCCGTCAGCCCCGCGGCCGTCGTCCGGCGCTT CCC

GGAGGTGAGATCCGTCGAGCTCAAGGGCAAGCCCCACTTCGCCGACTTCAACCTCGT CCC

CGAGGGCTGGGGCGGCTACGTCTCCCCCTGGATCACCACCCTGGCCCGCGCCTACCC TTG

GCTCGAGGAGATTCGGCTCAAGCGGATGGTGGTCACCGACGAGAGCTTGGAGCTGAT CGC

CCGCTCGTTCAAGAACTTCAAGGTCCTGGTTTTGTCCTCTTGCGAGGGGTTCTCGAC CGAC

GGGCTCGCCGCTGTTGCCGCTAATTGCAGGAACTTGAGGGAGCTTGACTTACGGGAG AGT

GAAGTGGAAGATATGAGTGGACATTGGCTCAGTCATTTCCCTGATTCATATACATCA CTCGT

ATCCCTCAACATTTCCTGCTTAGGCTCTGAGGTAAGCTTCTCTGCCTTGGAGCGCCT GGTGA

GTCGCTGCCCCGACCTGAGGTCTCTCCGACTCAACCGCACCGTGCCACTTGATCGCC TTGC

CAATTTACTTCGACGGCCCCCACAGTTGGCTGAATTGGGCACGGGCGTTTATTCTGC TGAA

CTGAGGTCTGATGATTTCTCGAATCTAGTTGGTGCTCTAGCTGGCTGCCGAGAGCTG AGAA

GTCTGTCTGGATTTTGGGATGTGGTACCTGCATATCTTCCAGCTGTATATCCCCTAT GCTCA

GGGCTTACATCGTTGAACTTGAGCTATGCTACCATCCAAAGCTCTGAACTTACAAAA CTTATC

AGTCAATGTCACAGTCTGCAGCGCTTATGGGTACTTGATTATATTGAAGACAGCGGT TTGGA

AGCCCTGGCTGCATGTTGCAAAGATTTACGGGAATTGAGGGTGTTTCCCTCTGAGCC CTTC

AACCGTGAAGGAAATGTATCTTTAACGGAGCAGGGCCTTGTGTCAGTGTCTGAGGGT TGCT

CCAAGCTTCAGTCAGTTTTGTACTTCTGCCGCCAGATGTCTAATGCGGCCTTACTTA CCATA

GCTCGGAACCGTCCTAACATGACTCGATTCCGACTTTGTATCATTGAACCACGTTGT CCTGA

TTATATAACTCATGAGCCACTCGATACAGGCTTTGGAGCCATTGTCCAACACTGCAA GGATC

TCCAGCGTCTCTCTCTATCAGGTCTTCTAACTGACCGTGTGTTTGAGTACATAGGGA CTTAT

GCAAAGAAACTTGAGATGCTTTCTGTGGCATTCGCTGGAGACAGTGACTTGGGACTG CACC

ATGTGCTATCGGGGTGCGACAGTCTTAGAAAATTGGAGATCCGGGACTGCCCGTTTG GTGA

CAAGGCGCTTTTGGCCAATGCTGCAAAGCTGGAGACAATGCGATCCCTTTGGATGTC TTCTT

GCTCAGTGAGCTTCGGAGCATGTAAGCTGCTTGGTCAGAAGATGCCCAGGCTTAATG TCGA

AGTCATTGACGAGAGAGGCCACCCGGATTCAAGGCCTGAAAGCTGCCCGGTCGAGAA GCT

TTACATCTATAGAACGGTTGCAGGTCCGAGGTTCGACATGCCTGATTTTGTTTGGAC AATGG

ATGAGGATTCTGCTCTGAGGCCTTCTTGACAGCTTTCATTCAACCGTTTGCTTTTTT TCCTCG

TGGCACTATGGTGTGGTGACTGTGACAGTCAAAGCAGGTACATGCTCTTCACCGCCC TCTTT

CATGCAGGTCTAATTTCTTTTTAGCTTAGTATTAGCAGCTGTTATTGGTGGTGACAT TAGCTG

TGGGAAGGGTATATGGAGGCTCAAGAGCTCTTTAGCCGAAGATTTTGCACTTGGCTG AGCT

ATGGATACCAATGCATTGTTAAATAAAAGAGGACCCTTTTTGCTTTTGCTGTTGTTG TTGTTA

TTGTTGCTGTTGTATGTGTATCAAGACATGGTTATTTAATTTGGGTTAAAAAAAAAA

41 CTCCTTCTTCTTCCTCTTCTCTCTCTCTTTCCCCCCAACATTTTCACGAACACCTGCCGG ACG

GAGAGAGACCTGCAGCTGGGTTGCCGGAGAGGAAGAGGGAGAGAGGGACAATGGCGC AG

TACGAGGAGGACAACGCCGAGTTCTACGTGCGGTACTACGTGGGCCACAAGGGGAAG TTC

GGGCACGAGTTCCTGGAGTTCGAGTTCAGGCCCGACGGGAAGCTGCGGTACGCCAAC AAC

TCCAACTACAAGAACGACATCATGATCCGCAAGGAGGTCTGGCTCACCCCCGCCGTC CTCC

GCGAGTGCCGCCGCATCATCTCCGAGAGCGAGATTATGAAGGAAGATGATAGTAACT GGCC

AGAACCTGACCGTGTGGGACGGCAAGAACTTGAGATTGTAATGGGGAATGAGCACAT TTCC

TTCACTACCTCAAAGATTGGTTCCCTTGTTGACGTGCAGACAAGCAAGGACCCTGAC GGGC

TTCGGATATTCTACTATCTTGTTCAGGACTTGAAATGCTTTGTGTTCTCTCTCATCT CCCTCC

ACTTCAAGATCAAGCCAATCTAAGGAGGACTTCTTCCAAGCATCTGAATCCCAATTG TTTGAT

CCTTTTGGCGGTAGCCTCGTGGTCTGTCATTGATTGAGCAGCATGCATATTGTGGTA TTGTG

CACTTTGAGTATTGACTGGTGGAATCTCCTTGTTGAGTTTTGGGTTTGTAACTAAAA GATGCT

TTTAACTCGAAATGCCAGACACCTCTCTCTCTCTCAAAAAAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

42 GGCATTGTTCCTTCGCAGTCGAGTCGAGTCGAGTTCGCTTCCCGCTGCCGCTGACGAAGG

GTCCCATCTGCTCCTGCTCCTGCTCCTGCTCCTGCTTCGGCTTCATCCCGCTCTCCT TTTCT

CTGCTTCTTCTTCTTCTTCGTCTTCTTCCGACCAATCCCCCAAAAGAGAAGAGGAGG AAGAG

GGAGGGATAAAGTAGGGGGAGGAGGGGTTGGAAATGGCGAGGAGAGCGGAGGAGGAG TA

CGATTACCTGTTCAAGGTGGTGCTGATCGGCGATTCCGGGGTCGGCAAATCCAACCT CCTC

TCCCGATTCACTCGCAACGAGTTCTGCCTCGAGTCCAAATCCACCATCGGCGTCGAA TTCG

CCACCCGCACCCTCCAAGTTGAGGGAAGGACTGTTAAAGCACAGATATGGGACACCG CTG

GCCAGGAGCGATACAGAGCGATCACCAGCGCCTACTACAGGGGTGCCCTTGGGGCTC TTC

TTGTATACGATGTGACAAAGCCGACTACTTTTGACAATGTGAGTCGATGGCTGAAGG AGCTG

AGGGATCATGCCGATTCCAACATTGTCATCATGCTAATTGGGAACAAGACTGACTTG AAGCA

CCTTAGAGCAGTGGCTACTGAAGATGCCCAGAGTTATGCCGAGAAAGAGGGCCTCTC GTTC

ATCGAGACATCTGCCCTGGAAGCGACCAATGTGGAGAAGGCTTTCCAGACTATTCTC TCAG

AGATATACAGGATAATTAGTAAGAAGCCTCTGTCCTCAGAAGATGCAGCCCCGGCCA ACATT

AAAGAAGGGAAAACCATTGTAGTTGGCGAATCAGAAGCCAACACGAAGAAGGCATGC TGCT

CTTCGTCTTGAAGATCATCCTATGTTCTTTTCCCTTACCATTGTGGTCCTTGTTTCC TTAGTTT

CTCTGCTGGTTTATATGTTGTCTCCAATTTGTTTTTCTTCTTTCTCTTTCTTTTCCA ATTTTTTG

ACTGTTTCCAAGATTATTATTGGGTCATTTGACGAAAAAAAAAA

43 GCTTTTCTTTTATCCCAACTCTCAAATTTATTCCCCGCCCACTCCTCCCTCATTTCCCCT GCA

CAGGAAAAAAGTCGGCTCACATATATAGCTTCCTGAATGCAATGGCAGTTGATTGCC TCACA

AGTAAMCCTCACCAGCCATGCCTCCGCAGCACAAAGATGAAGCCAGAGAGGATAAAA AAC

ATCTAGTTTTTGACGCCTCGGTGATCCGGCACCAACCCGACATCCCGAAACAGTTCA TTTGG

CCCGACGAGGAAAAGCCGTGTGCGAACGCCCCGGATCTCGCCGTCCCGCTCATCGAC TTG

GACGGGTTCCTCTCCAAAGACCCGAGTGCCTCCGAGGAGGCATCGAGGCTCGTGGGG GAT

GCGTGCCAGAAGCACGGCTTCTTCCTTGTCGTCAATCACGGCGTGGATGCTGGCCTC ATAT

CGGACGCTCACAAGTACATGGACAAATTCTTCGGGTTACCGCTCAGCGAGAAGCAGA GGGC

TCAGAGGAAGCTCGGTGAGCATTGTGGATATGCCAGCAGTTTCACTGGCAGGTTCTC TTCC

AAGCTCCCATGGAAAGAAACGCTTTCCTTCGGCTACTCCGCCGAGAAAAGCTCGGCC AATG

TCGTGGAAGACTACTTCAAGAACACCATGGGCGAAGAGTTTGAGCAATCCGGGAGGG TGTA

CCAGGACTATTGTGAGGCCATGAGCAGACTGTCTCTAGGAATAATGGAGCTGCTAGG AATG

AGCCTAGGAATCGGCAGAGACCATTTCAGGGAGTTCTTCGAAAGCAACGATTCGATC ATGA

GGCTCAACTACTACCCTCCGTGCCAGAAGCCGGACCTCACCCTAGGAACCGGTCCCC ACT

GCGACCCGACATCCTTAACCATCCTACACCAGGACCAAGTTGGCGGGCTCCAAGTGT TCGT

CGACAACGAGTGGCGTTCCATCAGCCCGAACTTCAACGCGTTCGTCGTCAACATCGG CGAC

ACTTTCATGGCTCTATCAAACGGGCTATACAAGAGCTGTTTGCACAGAGCAGTGGTG AACAG

CCGAACTCCGAGGAAGTCCCTCGCCTTCTTCTTGTGCCCGAGGAGCGACAAAGTGGT GAGA

CCACCGAGTGAGCTAGTCGCAATGTCCTGTCCGAGAGCGTACCCGGACTTCACATGG CCG

GTGCTCCTCGAGTTCACTCAGAAGCATTACAGGGCCGACATGAACACGCTCCGAGCA TTCA

CCAACTGGCTTCAACAGAGAACATCTGAACCAGTTCGGTGATGAAGATTTGTCACAA GTAGA

GAGATCTATTTGGAGGTCCGAAAAGTTGCGGCTAACAAAGGGGTGAAAGAGCCTCTC TGCC

AAAGCAAAGAAGATGACATTGACGACGACAAAGAAGAGAGATCAAAAGGGAAGTGGT GGGT

TTTTTTTAAAGGACGTTGGAGAGGGACAAACAGAGAGTTAGAGGAAAAGCCAAAATA TCTTT

TACCTTCAAGGGTACGTCTTCTGTAGCCAGATAGTACTGGCACCCATGATGGTCACG ATGAT

CAAAGGGCAAGAGATCAAGAAACATGAGAACCAATAAAGAGCTGTAATACATCAGCT AATTT

TTGTTTTGTTTTTTTCCTTCTCCTTTTGTCCTTGGTTAAGGTAGAAAAGTTTACCCC ACAGTAA

CCCCTGCCTTGATGTAAATTTTGCATTTTGG

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

44 GCTCGTGTCCACCTACAAGTCAAATTCCGCTTCGATTGTCCGGTCCGACTCCCCGACCCA A

GGAAGGAACGACGTCAAAAAAAAAAAAAAATACGAACTTTCTCTGCCTCAAGACTCG CTAGG

MGTTGTCTTCTTTGAGAGCTCCGATCGGCATCAATGGCTTCTCGCCGGCGCATGCTC CTC

AAGGTCATCATCCTCGGCGACAGCGGGGTTGGGAAGACTTCTCTGATGAATCAGTAC GTGA

ATCGCAAGTTCAGCAATCAGTATAAGGCGACGATCGGAGCTGATTTCTTGACGAAGG AAGTT

CAGTTTGAGGACAGGCTGTTCACATTGCAGATATGGGATACAGCTGGCCAAGAAAGG TTTC

AAAGTCTTGGTGTGGCTTTTTACAGAGGTGCCGACTGCTGTGTTCTTGTGTATGATG TGAAT

GTAATGAAATCATTCGACAATCTAAATAACTGGCGGGAGGAGTTTTTGATTCAGGCC GGTCC

TTCTGACCCTGAAAACTTCCCATTTGTCGTTTTGGGTAACAAGGTGGATGTCGATAA TGGCA

ATAGTCGTGTGGTTTCTGAGAAGAAAGCGAGGGCTTGGTGTGCTTCCAAAGGAAACA TTCC

TTACTTTGAGACCTCTGCCAAAGAAGGATTTAACGTGGAAGCTGCTTTTGAGTGTAT AGCCA

AAAATGCTTTGAAGAATGMCCAGAAGAAGAAATATATCTTCCGGACACCATTGATGT TGCG

GGTGGAGCACGGCAGCAGAGGTCCACCGGCTGCGAGTGTTGMGAGTCCMCAGTACAT C

MTTCCCTTGGGATGCGTATACGATGCGGCTCMGGTGTATCMTTCGTGTTACAGATAC CA

TTCTCTTATGTATTGTCAAMGCAGAGTAAAAAAAMTTCTTCCTAMGGATTGATGTAG AGA

ACCGTTGAACTTCCCAGTGTGCATTTGTATCATMGCCMTCAGGGAGACCTTGTTTGT TTTT

TCATCTTTTCACACCTATTTGGTTCCATGATATCTTTGGTCAQCCTGAAATTCTTAA TATCTTT

TCCTAAAMAAAAA

45 GGMTAAMGGGCATCTACATTGACTTGGATCTAAAMGATTCGATTTTTTGTATTTTTCCGA

GCTGMTTTCAGGMTTATAGCTTCCTTTCCAGTACCCATTGAMGAGCACCCCCGTGGG CC

GTCGCTGCTCCCTCGCAGATTCATGGAGTGAGAMTCTGMGGGGAGAACGCTGATGAT GC

AGATCCGAATGAAACCCCACGTTGGGTTCTTCCTCCCGGTTGCCCTGCATCGATCCC TGTC

GTCGCTTCCTCCGMTCCAGTCGCCTGACCCGTGCAGGTACGCTCAGTGGGACATTGA CCA

ACTCTCTTGTCCTMTTTTCCATCACMGCTACTATATGGGAGCTAGCTAGGCACCAGA GCA

GMGGTGTCTGTTCCGGCCMTACTACCTCGATTTGTCAGCTCCTATTTTATTGCTTGC TTGA

GAGTCTAATTCATATTCGTACATTAMCTCCCMACTCTTCCCTCGATTGCCACATCAT CAAC

CAGCAAAGACATTCAMACTCAAAGATGCTCACCATCTCGGATGAGAAACTCTTTCAC MCT

GCCTGCTCGCTCTCTACCTCATTGGACCGCCCACCTTCATCTCCCTACGATACATCC MGCC

CCTTATGGCMGCACCACCGCTCAGGGTGGGGCCCCACCATCTCCCCAGCCCTTGCTT GG

TTCCTCATGGAMGCCCCACTCTTTGGCTCACGCTCTTGATTTTCCCCTTTGGCAAAM CTC

CTCCMCGCCAGATCCCTCATTCTCATCTCCCCTTTCCTCTTTCACTACTTTCATCGA ACAAT

CATATATCCACTGCGCATCAGATCMGCGGTGGTCAGAGAAGTACTCAACCAMTGCTG CM

ATCGTTTTCCGGTCACTGTGGCCTTCATGGCATTTGGGTTCMTCTCTTGMTGCTTAC GTG

CMGCCAGGTGGGTGTCTMTTACGAGAGTGACGGTGCTGCTGGTGGGTGGTGGTTTTG G

GGGAGATTCTTGGTGGGATTGGTGATATTTGTTAGTGGGATGTATATGMCATGTCAT CGGA

CATGGTGTTGGTGGGGTTAMGAGGGMGGGMAGGGTATCGAGTGCCMGAGGAGGGTT

GTTCGAGTTTGTGAGCTGTCCCMTTATTTTGGAGAGATTGTGGAGTGGCTGGGATGG GCT

GTGATGACATGGTCTTGGGCCGGCTTCGGGTTCTTCCTCTACACGTGCGCCMCTTGG TGC

CTCGGGCTCGTGCAMCCACAGGTGGTATTTGGATAMTTTGGGGAGGAGTATCCCMGA G

CAGGAMGCTGTCATTCCATTCTTGTATTGATCAATTCATAAGGATGCTTGCAMCAGG GAA

ATGAAMATATGGATGAMCTGGACGTGATTTGTACCCAACGTTTCTTCTTGTTAGAGC TTTT

CCAAGAAAMTTTGTMTCCCCCTGMTMTGGAGTTACTATTGATCAGTGGATATTGCTT AC

TATGTTGTTCAAAAAAAAM

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

46 GATCAGGGGCGGGGCCGGTGGGGACAACGAGAAAGATTCTCTCTCGGTCGCCGCCGTCG

CCGTCGTGTCGCCGTCGTCGCCAGTCACTTCGCACTGTGTCTGCCGGTCTCCGCTGG AGC

TCCTCTGTACCGCTTTAGCGAAGTCTACTCCAGCAAGTCAAGCAGACTACCTAAGCA ACCCG

CTCCTCTCTCTCTCTCTCTCTCTCTTTCTTTCTCTCTCTATCTCATCGATCGAGTTC ACTCCC

GAACGGAGAGAGGCGGAGCGGAGGAAGGAGGAGAGAAAATGGCGGAAGCGAAGACCG TG

CACTCGCCGCTCGTCACCTACTTCTCCATGCTGTCGCTCCTCACCCTCTGCCCTCCT TTCGT

CATCTTGCTATGGTACACGATGGTGCATGCTGATGGGTCTATCGTCCAAACTTTTGA TTACC

TGAGGCAGCATGGACTGCAAGGATTCCTAGACATATGGCCCAGGCCGACTGCCGTCG CTT

GGAAGATCATCGCCGTTTATGCTGCATTTGAGGCGGCGCTGCAGCTCCTTCTTCCAG GAAA

GACAGTCAAGGGCCCTATATCTCCTGCTGGGAATCAGCCAGTGTATAAGGCAAACGG AATG

GCAGCATATTTTGTGACCTTGATCACCTATCTTGGCCTTTGGTGGTTTGGGATTTTT AACCCC

ACGGTTGTTTATGATCACTTGGGCGAAATATACTCCGCACTCATTGTTGGAAGCTTC ATCTTT

TGTATTTTCTTGTACATTAAAGGTCATGTGGCACCATCATCTACCGACTCTGGTTCT TCGGG

GAATATAATAATCGACTTCTATTGGGGTATGGAGCTCTATCCTCGGATTGGCAAGGA CTTTG

ATATTAAAGTCTTCACAAATTGCAGGTTCGGAATGATGTCTTGGGCAGTTCTTGCTC TAACCT

ATTGCATAAAGCAGTACGAACAGAATGGAAMGTTGCTGATTCAATGCTCGTGAATAC AATA

TTGATGTTAGTGTATGTCACCAAGTTCTTTTGGTGGGAAGCCGGCTATTGGAACACA ATGGA

TATTGCACACGATCGAGCTGGCTTCTACATCTGTTGGGGATGCTTGGTATGGGTCCC ATCCA

TCTATACCTCTCCTGGCATGTATCTCGTCAATCATCCTGTTAACCTGGGAACTCAGC TCGCA

CTATATATTTTGGTAGCAGGCATTCTGTGCATATATATCAATTATGATTGCGACAGA CAGAGG

CAAGAATTTCGCAGAACAAATGGCAAGTGCTCAGTATGGGGGAAGGCTCCATCAAAG ATAT

CGGCTTCGTACACTACAACATCTGGAGAGAACAAAACTAGCCTCCTCTTGACTTCAG GATGG

TGGGGCTTATCACGTCATTTTCATTATGTGCCCGAGATTCTTGGAGCCTTTTTCTGG ACTGT

CCCTGCACTATTTAATCATTTTCTGCCTTACTTTTATGTGATCTTTCTCACAATCCT ATTGTTT

GACCGGGCAAAAAGGGACGACGATCGGTGTCGATCAAAGTATGGGAAGTACTGGAAG CTAT

ATTGTGAGAAGGTTCGATACCGAATTATTCCTGGTATTTACTGAGGTTCAGCAAGAA CTCCT

GTATGGGGAAGATATGGTCGGGCGAAAGGAGTCCACATGGATCGGCTTTGGCTCGTT CTCA

TGTACTTCAGAAGATGTCCCTGTACTTGGTTTTATAGGAGATGCCAGCGGTAGAGCT ACTTT

TCGTGTTTCATGCATGCAGCAGCATTTAACATTGCGTTTATCTTTGCTACTCCAATT CGGAAT

GACTTTGTATCGAACTCAGAGTATCGGCACTCAGTAACTGTAGCTTTAGTTTGAACC GGCTG

CCCTGAACGTTGAGGTTTTTCAGACTGCAGTCTATTTCTGCTTGTATGTTGACTTGA CGTAGA

AATTGCGTGGTGGGACTTATTTCGAACGGTGTGTGATTTAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

47 GCTCTCTCTCTCTCTCTCTACTCTTTCTCTCTCTAACTCTCCGTCCGCCATTGAAGCTTC TCC

TCCAGCGCGGAACCCTAGAGGCATGAAGGCGATGAGGAGCACGAAGCCGCTGAAGCC CCT

CAAGCTCGCGGTCCCCGCTCCCGACGCCCCGATCGCCTCCTTCTTGACTGCGAGTGG CAC

GTTCCATGATGGGGATTTGCTATTGAACCACAAAGGTCTGCGGCTCAAGTCTGAAGA AAAG

GAGTCTTGTCTTTCCAATGGTAAGGAACTTGATCTTGACTTCTCATTGGAAGACCTT GAGACT

ATCAAAGTCATAGGAAAGGGAAGTGGTGGTGTGGTACAACTTGTTCGCCATAAATGG GTTG

GAAAACTATTTGCTCTAAAGGTCATCCAGATGAATATACAAGAAGAGATCCGTAAAC AGATT

GTACAAGAGCTAAAGATAAATCAAGCTTCTCAATGTCCACATGTCGTGATTTGCTAC CACTC

GTTCTACCACAATGGAGCTTTCTCCTTGGTGTTAGAGTACATGGACCGTGGATCCCT GGCTG

ATGTGATCAGACAAGTTAAGACTATTCTAGAACCATATTTAGCAGTGGTCTGTAAGC AGGTC

TTACAAGGTCTTGTTTATTTGCACAATGAGAGACATGTAATACACAGGGATATAAAA CCATCC

AATCTGCTTGTGAACCACAGAGGTGAAGTCAAGATTACAGATTTTGGTGTCAGTGCT ATGCT

AGCGAGCTCAATGGGTCAACGAGATACATTTGTTGGAACTTACAATTATATGTCGCC TGAGA

GGATTAGCGGGAGCACATATGACTATAGCAGTGATATCTGGAGTTTGGGCATGGTAG TACTT

GAATGTGCTATAGGACGCTTTCCTTACATGCAATCTGAAGATCAGCAAAGCTGGCCA AGCTT

TTATGAGCTTTTGGAGGCGATCGTCGAAAGTCCACCACCTTCTGCTCCAGCAGATCA GTTTT

CCCCAGAGTTCTGCTCATTTGTATCTTCCTGCATACAAAAGGACCCTCAACAAAGAT CTTCG

TCTTTGGACCTTTTGAGTCATGCTTTCATAAAAAAGTTTGAAGACAAAGATATCGAT CTTGGG

ATTCTCGTAGGTAGCTTGGAACCTCCCGTAAGTTTTCCGAGATGCTAAGCTGTGGGT GCTTA

TGGGGTAAAATCCTCTTACTCATATGTATCCTTCCTGCGCGTGGTTGAGGATTCGCA TAGAG

TGACTTCGCTTGAGCAATTGAGCAAATGATGATAGAAGTCTCTTACTTATAGAAAGA GCAGC

ATGCCAAGGTTCTGTACTGAGAAAATTCTGCCTTCTACTTAATCCTACCAGCTTAAG TGAGCT

TACCCGAGATGTACTTGTTTTGGCTCCATAACCTTAAAGAGCTGACTCCTGAAAAAA CAAGA

AAACAAGAAGACAGGCATCTATAATCCATGCTTAGCCTTTATAATCCATCTTCTTAA ACATTTT

CTGCTCATGTATGCGAGAAGAAAGGCAGATGCATCAAGCCTTTTCTGATGCTGCCCT TGAAC

AATTCCCAAAAAAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

48 GAAGAAGGGGCCGGGCTCGAGCCCAGAGAGAGAGAGAGAGAGAGGGCCCACGGAGGGC

CCACGGAGACGCTCCCGCGCGAGGAGGGCTTTCTGTCGCGCTGCAGGAGGAAACGGA CA

GCGAACGCTGCTTCGCTCCCAATCTTTCAATTTGTTTGAACTTTTGAGTTGAAAGGG CCGAA

AGGCGAATCTCAATGGCTTGGCTTCCATCACTTCCCTGATTTCTTCCCTCCATTTCC ACCCC

CACTCTCCCTCCACCCACCATTCCGAGCGCACCAGCCGCGTCCGACCMTCTTGGGTT GCT

CTCGTTTCTACCCAACAAGGTTTCCTTGGGATGGATTCAACCACACACAGTTTCCAG CGTCG

GCCACTCTCGATAAAACTCTGGCCGCCTAGTCAAAGTACTAGGATTATGCTTGTGGA GCGTA

TGACAAAAAATCTAATAGCTCCATCTGTATTGTCTAGAAAGTATGGCCTTCTGAGTA AGGAAG

AGGCCGAGGAGGATGCCAAGCGCATTGAAGAGAGCGCATTTGCTATCGCCAATCAAC ACAT

GGAGAAGGAGCCAGATGGTGATGGGAGTTCTGCAGTACAAGTTTATGCTACACAGTC AAGT

AAACTTATGCTGGAAGTCATCAAAAGAGGCCCAAGGATGAAGGTGGATGGCGAGGCC ATTT

TACCTGCAAAAGCTATTGCTGCAAGTGAAACTGTCTTTGACATCTCTGGAGGTCGAC GGGC

CTTTATTGATGCGGAAGAAGCTGAGGAGCTTCTTAAACCATTGAAGGCACCAGGGAA CTTCT

ACAAGAAAATATGTTTCAGCAACAGAAGCTTTGGCTTAGATGCTGCCCGAGTTGCTG AACCT

TTTCTAGTATCTGTCAAGGATAAATTGACAGATGTTGATCTGTCAGATTTTGTTGCA GGAAGA

CCGGAAGCCGAAGCTCTTGAAGTGATGAATATTTTTTCTTCAGCCCTTGAAGGTTGC AACTT

GAGGAGTCTGGACCTATCCAACAATGCATTGGGAGAAAAGGGTGTCAGGGCATTTGG AGCA

CTTCTAAAGTCTCAAAATAATCTCGAGGAACTTTATTTGATGAATGATGGTATCTCT GAGGAA

GCTGCTCTGGCAGTTTGTGAGTTACTTCCTTCTACTGAGAAGCTTAGGATCCTTCAC TTCCA

TAATAACATGACTGGAGATGAGGGAGCGCTTGCCATTTCTGAGATTGTGAAGCATTC TCCGG

TGTTGGAGGACTTTCGATGTTCTTCTACGAGGGTAGGCTCAGATGGTGGAGTTTCTC TGTGT

GATGCACTTAGCGCATGTTCCCGGATCAAGAAGCTTGATCTGCGGGATAACATGTTT GGTGT

CGAATCTGGAGTTGCTTTGAGCAAGGCTATCCCTTCATTTGCTGACCTAACAGAGGT GTATT

TTAGTTATCTAAACTTGGAGGATGAGGGCACAGAAGCTCTTGCCATTGCTCTCAAGG AATCT

GCACCTTCCCTTGAAGTTTTGGAAATGGCAGGGAATGACATTACTGCAAAAGCTGGT GCTGT

TTTAGCAGCCTGTATTGCAGCAAAGCAGTTTTTGACCAAGTTAAATCTGTCTGAGAA TGAATT

GAAGGATGAAGGTGCAATATTGATCGGTAAGGCTTTGGAAGAGGGCCATGGACAGTT GGTT

GAAGTTGATTTGAGCACAAACTCGATTAGAAGGGTTGGAGCAAGAGTCCTAGCCCAG GCTG

TTGTGCAGAAACCTGGATTTAAAATGCTGAATATAAATGCTAATTTCATTTCGGAGG AAGGG

CTTGATGAGGTAAAGGATATATTCAAAACTTCTCCTAATATGCTTGGTCCACTTGAT GAGAAT

GACCCTGAGGGTGAAGATTTTGATGAGGAGGCTGATGAGGAAGGCGCTGGTCACGAG GAT

GAATTGGAAGCCAAGCTCAAGGATCTTGAAATAAAGCATGAGGAGTAGTTTGGTTGA TTCTC

TGATTGTTTGATTGAGAGAGTTTTTAGTAATTTTAAAACTGGTTCAGCTCTATTTGC AATGTCT

AGTTGCTTAATTTTAGGTTAGTTAGGTGATGTTCTTGTCAAATCTGTCATTGCATGT GAAGTT

CAGAAACATGTAAGATGATGATTTTTCTTGCTGGCAAGTTTAGCAGATCATCATAGC AAAGCT

CCATCTGAAGGGTATTTGATAAGGTTACTTGGGAAAAAAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

49 CTCTCCTGGTTCAAAAACCTAGAGAGAGAAAGMGAGAGAGAGAGAGAGAGACGGAGACC

GCAGGAAATTCATCGACGAGAGCCGCTCGTCTCCGATCCGCCGCCGCGCGATCGCCG ATC

GATCCGGCCGGAGCCGTGCGGAGATCGGTAGGGTAGATTGCCGAATCGGGGCTGGAC CT

CGCGACCCGCGATCGGGATTCGGCACGGAGGTCCTGCGCGCGATCGGATCTGGTGGG AT

CGATTTCGAAGGGCGTAGAAGGAGAAGAAGCAGGAGGAGGAGGAGGAGGAGGAGAAG GA

GGAGAATGGTGAAGCTCACGATGATCGCCCGCGTCACCGACGGCCTCCCGCTCGCGG AGG

GGCTCGACGACGGCCGCGACGTGAAGGACGCCGAGTTCTACAAGCAGCAAGTCAAGG CGC

TGTTCAAGAACCTCTCCAAGGGCCAGAACGAGCCCTCCAGAATGTCGGTCGAAACCG GCCC

TTACTACTTCCACTACATCATTGAAGGGCGCGTCTGTTACTTGACCATGTGCGATCG ATCTT

ACCCCAAGAAGCTCGCGTTCCAGTACCTGGAGGACCTCAAGAATGAATTCGGGCGCG TGAA

TGGGGCGCAGATCGAAACCGCGGCTCGGCCGTACGCCTTCATCAAATTCGATACGTT TATA

CAGAAAACAAAGAAACTTTATCAGGACACTCGTACCCAGAGGAACATTTCGAAGTTG AATGA

TGAACTCTATGAGGTCCACCAGATTATGACCCGCAATGTCCAAGAGGTACTTGGCGT TGGC

GAAAAATTGGACCAGGTCAGTGAAATGTCTAGTCGGTTAACATCAGAATCTCGCATA TATGC

CGACAAGGCCAGAGACTTGAATCGACAGGCACTAATTCGAAAATGGGCCCCAGTTGC CATT

GTTCTGGGAGTGGTCTTCCTTCTCTTCTGGGTCAAATCAAAGATATGGTGATGTGAC TGCCT

TGCCTGTACTTCTGTTCTACTGCAGTGGGCTGCTGGGTTGCTGAGAGATTCATTCTC AACGA

TTTTAAATGGGGCACGGGATTTTCACAGAGAATCATATGCGTTCAAAAGTTAGTGTA GTTCTT

CTAATTGCATTTTGTATTGGATGCTTCATTCCTTATGCAGTTGTGGCAATAGATTTG CCATGT

TAAGTAGTGAATAGAGAACCCTCCCTTAAGACAGGAGCAACATCAATATCTTATTGT CGACA

AACTAGCAGAGTGTTTTCCGTACAGGAGGCTGCGTATAACTTTTGTTCATCAATACC TATAAT

CATCTCTTATAGTAAAAAAAAAA

50 CGCTCCTCTCTACAACAATCTCGTGCTCTTTTCCGGCAAACTCCTCCTTCGTCTTTGTCC ATC

TTTCTTGCTATATTATAAGTTACCAAGTCAAAAACCCGACAAGCCTTTTTTCTTTGA AGACGAT

GAGTTACGTTTCAAGCAACAGAAAGCCACTGTTGTCTCGGAAAGCAACCAACGACGG TCAT

GCCGAGAAGTCTCCCTATTTCGATGGGTGGAAGGCCTACGACAAGGACCCATTTCAT CCTA

CGCAGAATCCCAGTGGTGTCATCCAAATGGGTCTTGCAGAACATCAGCTCTGTTTCG ACTTG

GTTCAAGAATGGCTCGTCAGCAACCCAGAAGCCTCCATCTGCACTAAGAAAGGAGTG GACA

AATTCAGGGACATTGCCCTCTTTCAGGATTATCATGGCTTGCCCGCGTTCAGAAACG CTGTG

GCGAAGTTCATGGGGAGAGTGAGGGGGGACAAGGTCAAGTTTGATCCCGACCGGATT GTC

ATGAGCGGGGGAGCCACAGGAGCTCACGAGATGATCACATTCTGCCTGGCTGATCCT GGC

GATGCGTTCTTGGTGCCAACCCCTTACTATGCAGGATTTGATCGAGATTTGTGTTGG AGGAC

TGAAGCACGACTTCTCCCGGTAGTCTGTCACAGCTCTAACAATTTCAAGGTCACCAG GAAG

GCTTTGGAAGAAGCATACGCAAAAGCTGTTGAGGCCAACATCAGCGTAAAAGGGTTG CTCT

TAACCAATCCATCAAACCCACTAGGGACCATCTTAGACCGAGACACGTTGAGAGAAG CCAT

GAGCTTCATCAACGAGAAGAACATCCACCTCATTTGCGATGAGATATATGCTGCTAC AGTCT

TTCGTCAGCCTGATTTCATAAGCATCGCAGAGATAATCGAGGAAGATCAAGAATACA ATCGC

AACCTCGTGCATATAATTTATAGCCTCTCAAAAGATATGGGTTTCCCTGGCTTCAGG GTTGG

GATTGTGTATTCATACAATGATGCCGTGGTGGAGTGCGGCCGGAGGATGTCCAGCTT CGGT

CTAGTATCCTCCCAAACTCAGTACCTAATTGCATCCATGTTATCGGACGATCAGTTC ATTGG

GAAATTCCTGTTGGAGAGTGCGGAGAGGTTAGAGACGAGGCATAAGAATTTCACTGA CGGA

CTTCATCAAGTAGGCATCAAGTGCTTGAACGGCAATGCGGGTCTCTTCTTATGGATG GATTT

GAGGGAGCTCCTGATGGAGAGCACCGTAGAGGCAGAGACGGCTCTGTGGCGGGGCAT AAT

TAACGAATTCAAGCTCAATGTCTCACCGGGTTCTTCCTTTCACTGCTCAGAGCCAGG ATGGT

TCAGAGTTTGCATTGCCAACATGAATGAGGAGACCATGAAGGTCGCTTTAGCACGAA TCCG

AGAGTTTGTGCGGAGGAATGGCGATAAGCTGAACAGGAAGGAGAAGTGCCGGCAGAG CGA

CCTAAGGCTCAGACTCTCGTTCCGAAGAATGGATGATGTGTTGAGGTCGCCCTGCAT TATGT

CCCCTCACTCGCCCATCCCTCAATCACCACTGGTTCGAACCAGAACTTGAAGTTGGC AATC

GCGTGATTCTACAAACGGGCATTTTTCCCATTAAATCCAAAGCTTTCCAAATGTAAA ATAGGG

AATTGTATTCTTTATTTGCTTGTAACTGGGTGCAGTGCAGAATGCATCCTAATTTTT CTGCAC

CCCATTTTGTTCATTCTTTCATCAGGCACGGTATTTTAATTTTTTCCTTCTGTATAA TCCCTAA

GATGGCCCTAAGTTCCATCAGGATTGACATTTTCAACAATATTCAGACTGTCGTGTT GTTTTC

AAAAAAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

51 CTTTAAGTTCATCGTATCCCCTTGTCCTTTTGTTCATGGATTCCGGAAACTCACGGAAGA GAA

AATTTGCAGGAATCCTTTACCTAATTATCTTGCGGTGCATGCGTAGGTATCCACCAG TTTCAT

CACCACGCACTTTCAGTTCTCCCGATCCCCCTTTTTAAACCCCCTCTCTCTGCTCAC GCCCT

TCTTTCAAGATCTGATCAAGATTTTTATCTATAGATTCTTCTTTATTTCAAGATAAG CGATTCG

TTTGGTGTGTCTTGCAAGATCTGAATGGACCTTGGAGCTTGCAAGAACCTCTCCTCT GTCGA

GCCGGTTATGGGCTTGATCCTTGGTGGGTTTTGGCGGAGGAATTCAAGAAAGTCGGC GGTT

CTTTCTTGAGTGGTGAAACAGGGGAATTCCTTCCTCCTGTTGTTGCCCTCTGAACGT TCTTG

CGTCTCTCTACTTTCTGGGAAAATAGCGAGTGGGAGAGCTGAAATCATGTGAGGGGA GAGA

AAAGGAAAAAAAGGTTTTGAAGAATCTGGCGCTTGGCTGTTTCGTGTTTCGTGGTGG GTCTG

TTCTGGAAGAGGAGCCCGGAGAAGGTAAAGGATAGAATTTTATACTCATCAAGAAAG GAGAT

CAGAGGAAAACCGAAAAGGGGCAGAGAGCATAAGCACAGTTCCTCACAGCAGGAGCG GCA

AGGGAATCCATGGCGACTCTGGTCGAGCCCCCGGATGGAGTTAGGCAGAGAGGGAAG CAG

TACTACTCAATGTGGCGGACCCTGTTCGAGGTGGACGCCAAGTACGTCCCCATCAAG CCCA

TCGGGCGAGGGGCGTACGGCGTGGTGTGCTCGTCAATCAACCGGGAGACACACGAGA AG

GTCGCCATCAAGAAGATCCACAACGTGTTCGAAAACCGGATCGACGCCCTCCGGACC CTGA

GGGAGCTCAAGCTCCTGCGGCACATCAAGCACGAGAATGTGATCGCCCTCAAGGACG TCAT

GCTCCCGGTCCACAGCGCTAGCTTCAGGGAGGTGTACCTGGTTTACGAGCTCATGGA CACC

GACCTGCACCAGCTCATCAAGTCCCCGCAGCCGCTGTCCAACGAGCATTGCAGGTTC TTCA

TTTTTCAGTTGCTGAAAGGGCTGAAGTATCTGCACTCAGCCAACGTTCTTCACCGCG ACCTC

AAGCCCGGAAACCTCCTGGTGAACGCCAACTGTGACCTGAAGATATGCGACTTCGGA CTCG

CGCGGACCAACCAAGGCGACGGGCAGTTCATGACTGAGTACGTGGTCACGCGCTGGT ACC

GTGCCCCTGAGCTGCTGCTCTCATGCGACAACTATGGGACCTCAATCGACGTCTGGT CCGT

GGGCTGCATCTTCGCCGAGATCCTCGGGCGCAAGCCCTTGTTCCCCGGGACAGAGTG CCT

CAACCAGCTGAGGCTGATCATCGACACGCTGGGAAGCCAGGGGGAGGAGGACATCGA GTT

CATCGACAACCGGAAGGCCCGGAGGTACATCAAGGCGCTGCCCTTCTCGAGGGGCAC CCA

CTTCTCCCAGCTGTACCCGCAGGCCGATCCCCTGGCGGTGGACCTGCTGCAGCGGAT GCT

CGTGTTCGACCCGAGGAAGAGGATCACAGTGACGGAGGCCCTCCAACATCCGTACAT GGC

AGGCCTGTACGACCCGCGGGGCAACCCGCCGGCTCAGTACCCGATCAACCTCGACAT TGA

CGATAGCATGGAGCAGCACATGATTAGGGAGATGATGTGGAACGAAATCCTTCACTA CCAT

CCTCATCAGTATGCTTCCCTCCATGGATAAAATAGCGGAATCCTTCACCATCGACAT GCCAG

AGCAAGAATTTTCTATCCTCTGTTCCCTGAATTTTCCCCTGAAACTTTCTTGTTGGT TCCTGC

ATTGAGAGAGACCTAATTGCTTGATGTCCTGTAATTTGTAAAAAGTTGCAATGGCCA CACCA

ACTAAGATAGCACATTGCAATTTCTTTAAAAAAAAAA

52 CTCGTTGCTTCGCGGTCGAGGGAGGGCGGGGGGGGGATCGACCGGATGGGGCAGCAATC

GCTGATCTACAGCTTCGTGGCCCGGGGCCCCGTCCTGCTGGCCGAGTACACCGAGTT CAG

CGGCAACTTCACCAGCGTCGCCTCCCAGTGCCTCCAGAAGCTCCCTGCCACCAGCAA CAA

GTTCACCTACAACTGCGACGGCCACACCTTCAACTACCTCGTCGACGATGGCCTCAC TTACT

GTGTGGTTGCAGTTGAGTCTGTTGGGCGCCAGATTCCAATGGCTTTCCTTGAGCGGA TCAA

GGAGGACTTTACTCACAGATACGACGCAGGAAAAGCTGCAACAGCATCTGCTAATAG CTTG

AACAGGGAGTTTGGGCCTAAACTCAAGGAGCACATGCAATATTGTGTTGATCATCCG GAAG

AGATCAGCAAACTTGCTAAGGTGAAAGCTCAGGTATCAGAAGTGAAGGGAGTAATGA TGGA

AAATATTGAGAAGGTTCTTGATCGTGGTGAAAAAATCGAACTTCTGGTTGATAAGAC AGACA

ATCTTCGTTCTCAGGCTCAAGACTTCAGGCAGCAGGGAACCAAAATGCGAAGAAAAA TGTG

GCTGCAGAACATGAAAATAAAGCTGATAGTTCTGGGCATTATTATTGCTTTGATTCT GGTCAT

TGTTTTATCTGTTTGTCATGGCTTCAATTGTGGTCATAAATAGTGGAGTGGTGCTGC TAATAG

GTTCTTATGAACCTGTCTTGAAGGTATTTTGCCTGTAAGTTTTCTTTCCTCTTTTGT TCTTTAC

ATGGTCCTTCATTATACTATAGCCTATAGAAGAAATACATTTGCATGTATAGTTTGT ATTCTTG

GACAAGTTCTATAATCATCGCGCCCCGGATTGTAATGTCAGCGACCTATGAGTGCTG ATAAA

AAAAAAA

W

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

53 AGCTATTATCCTTTGCTTCCAAGTGCTTCTCCGTCGTACTTGGCGTGTATAAGTCGAATC TC

GCCTGAATTTGCTGATGTTTCTCTAGATCCTTAGATTAAGGTTTGATCTGTGTATAT GCTGTG

TCGTTGCCTGAGAATGGTTCTGGGTTTGATGATGGCGATATTGGTCGAGGCGGCTGT GCTG

TGAGATTCTTTGTCGAGATCGCCGGTTGAGCTTTTCGGGAGTTTGTGTATTGTTTGG AGGTA

GTTTTGCGAGAAATGTAGGACATTGATGTCGTCGTTGAGTTTAATAACTTAGTTCTG TTCAGT

TTCTTGGTTTTCCGTGGCAGAACGGCGAGTGTGGAAATGGCTGATGTAGCGGGTCGT CGTT

GAGTTTATTAACTTAGTTCTGTTCAGTTTCTTGGTTTTCCGTGGCAGAACGGCGAGT GTGGA

AATGGCTGATGTAGCGGGTCTGACTGAAGCGGCGGGGTCCAGATTCAGTTCGCTCGA GTT

GATTGGGAGAGGATCTTTTGGAGATGTCTATAAAGCATTTGATAAGGAGCTCAACAA AGAAG

TTGCTATCAAAGTTATTGATCTGGAGGAGTCAGAGGATGAAATTGAAGACATTCAGA AGGAA

ATTTCTGTTCTATCACAATGTCGATCTCCATATATTACGGAATATTATGGTTCCTAT CTCCACC

AGACCAAGCTATGGATAATAATGGAGTACATGGCCGGTGGCTCCGTTGCTGATCTAC TTCAA

TCAGGTCCACCTCTTGATGAGATGTCCATAGCCTGTATTTTACGTGACTTGCTGCAT GCAAT

CGAATATTTGCACACTGAAGGGAAAATTCACAGGGATATTAAAGCGGCCAACATTTT ATTGA

GCGAGAACGGTGATGTTAAGGTTGCAGATTTTGGTGTTTCTGCTCAATTAACTAGAA CTATAT

CAAGGAGAAAGACATTTGTCGGAACCCCATTCTGGATGGCTCCGGAGGTAATTCAGA ATTC

GGATGGGTACAACGAGAAGGCAGATATCTGGTCTCTAGGGATCACTGCGATTGAGAT GGCA

AAAGGTGAACCTCCGCTTGCAGATCTTCACCCAATGAGAGTTCTTTTTATCATACCT CGAGA

AAATCCCCCACAGCTGGATGAGCATTTTTCTCGTTCCATTAAAGAATTTGTTTCCCT GTGCCT

GAAGAAAGTACCGGCAGAGCGGCCCAGTGCCAAGGAACTTCTGAAGCACCGTTTCAT AAGA

AATGCCAGGAAGAGTCCAAGGCTTCTAGAGCGAATAAGAGAGCGTCCAAAATATCCG ACAG

TGGAAGATGGAGAAACACCTATGATTGGTAAAGGTGTAGTGGAGGGATCAGACACTG TGAA

GATTAGAAGAGACATAAAAGGAGAAGAAACAGTAAGAGCCAGTAATCAAGGGCGAGG AGGG

AAGAATACTGGATGGGATTTCAGCATTGGTGGAGTGCAGGGAACAGGGACTGTTAGG ACCA

ATCTATTGCCACCTCAAGTCAGAGAGAGGAAATCAGAGAATTCCCACAATCAGGCTA CCCCT

AGAAGAGTGGCGGATGGTGGTAACTCATGGTTGTCTGCATCTGGAAATTCACCTCAG GCTG

CAGAAATATCACTTCGGAAAGATGCTAGAGATTTGCATTATAATAATCACCACGATG ACGAA

GATTCATCTTTGAGCGGATCGGGTACGGTCGTGGTACGAACTCCTAGAGAATCTCAA CCAT

CACCCTTGCTTCGCGATCAAAGCACTCTGTCTAGCAGCTCGTACAGTTCTGTTGAAG ATGCT

TCTACAACAGGAACTGTAGTTTTCCGCGGTCAACATGATGAGTCTGATTCTCCTCGG ACACC

AAAATCGAGACTCGGGATTCAGGAGAGAAGTTCCAGTGCTTCACTGGAAGACAGTGC AGCA

AACCTTGCAGAGGCTAAGGCGGCTATGCAAGGCGCTTTTAAAAGAGGAAATGCAAGA GAAA

AGAGATCTGTACTAGGTAAGTTTAATGACGGGCAGGAAMTGGGAATAGAGAACAACT TACA

AAAAGCCCTGATTCGTCGAGGAATTCCTATGAGTATTTTGATGCTCATAAAGTTCTC CCGAG

GTCCCGCCAAGCAAGCGATGATGAGGACATTGCAAAAATTTTATCTTCATCTGCTCC ATTAT

CGGTTCTGCTCATCCCTTCCTTGAAAGAGACAACTGGTGATGATTCTGATGGGCCAG TTGTC

CATGCTGTTTCAACCTCACTCACTAACTTAGAGCGCATGAAGCCAGGATCATGTGAG GTTCT

TATAAGCAAGTTGCTACAGAGATTGGCAAGTTCAAAAGAATCCTCGTTGAAAGACTT GCAGG

ATCTGGCAACTCACACCTTTTCCAAGGGCAAGATATCCCCAGAAAAGTCGGGAAATG CGAA

CACTGAAGCTGATAATCGCAAGAAACAACAGAACAAAGAATTCAATTCTAATGCTAA TTTAAG

CCCACTAGCAAGATTTTTGCTCTCAAGATGGCAAGGCCAAGTATCCCGAGATCTTAA CCCAA

CTTGAGAGAGAAGAAGAGAATAGTATCTATTTGTTTGTATTGTGCTTCGTGTCGATG CATTTA

TTCTGATTCACTGTACATAGAAATGATAGTGTATTTATTAGCAACCAACCTTTGTCT GAGTAA

ATTGCCTCTGATGGTAAGAGTTGCTGCGCGACTAGGAGGTTTGTTGTTGGTGCACTA ACAAT

GTAAAAAAAGACAAAATGGACCATCATTCTTATTTATCGATGGTTGAATTTTGGCTT TTATTTT

CTCGCCAGAGCTTTCCCGCCGTTTTCGATCAATACAAAGAAGAGCAGTACCATGGAT TTGAC

AGAGTAAAAAAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

54 AGAAAATACAGAAATCTCAGCACGATCCCCATCTCCTCCTTCGCCAAAGTCGTTGGGAAC TT

CCCCCCTTCTCCCTCTCGCTCCGTCCACGAAGCAAGCAAGCTCTCCGCGAAGATCCC TTCC

TTGTTGTTACCAAATTGGTTGAAGCTTCTTGTGGGTTGCTGGACCTGCAGATTTTGG TTAATA

AATGAGTCAGAAGGGCCTTATATATAGCTTTGTGGCGAAAGGGACTGTTGTTCTGGC CGAG

CACACGCAATTTTCGGGAAACTTTAGTACTATTGCTGTGCAGTGCTTGCAGAAGCTG CCTTC

TAATAGCAGCAAGTACACATACTCCTGCGATGGGCACACATTTAACTTCCTAACGGA TAGTG

GATTTGTTTTCCTGGTTGTTGCTGATGAGTCCGTCGGAAGAAGTGTGCCTTTCGTGT TTCTT

GAGCGAGTGAAGGATGACTTTATGCAGCATTATAGTGCCAGCATTGCAAGTGGCGAC CCAC

ATCCACTTGCAGATGATGATGAGGATGACGATTTGTTTCAAGATCGTTTTAGCATTG CATACA

ACCTTGACCGAGAGTTTGGGCCAAGACTTAAGGAGCATATGCAGTACTGCATGAGCC ATCC

AGAGGAGATGAGTAAGCTATCCAAATTGAAGGCTCAGATATCAGAGGTCAAAGGGAT TATG

GTTGATAATATTGAAAAGGTGTTGGACCGTGGGGAGAGAATTGAACTTCTGGTTGAC AAAAC

AGAGAACCTACAATTCCAGGCCGACATTTTCCAAAGGCAAGGAAGGCAACTGCGTAG GAAG

ATGTGGTTTCAGAATCTCCAAATGAAGGTTGTGGTGGCTGGAGCAGTTGTCATAGTM TATT

CTTGCTGTGGCTTATAGCAAAGTGGGGAAGTAAATAAAACTTGTTCTCAGGGTCGAC GCGG

CCAAGGTACAATATGATTTTGTATCTGGATATGTTTGTTGGTATGTGGAGCTAGCCT ACCACT

TAGGATTT

55 CGGCACTCGCCATCGGAGCAGCTGGTGGGATTGCTCGCGGCTTTCTGCTCATGGAAGGAG

AAGAAGAGCAGAAGCCGGCGGCGACGAAGCGGAGGAAACCGAGATCGGGAGCGCCTT CT

TCCGCCCCGATCAACAATCTCGATGACGGGTGCCTCATGCACATCTTCAGCTTCCTT TCTCC

TATTCCAGATCGTTATAACACCGCCCTCGTTTGCCACAGATGGTGTTACCTGGCATG TCACC

CTCGGCTGTGGCTACGAGTAGACCGGTCTGTAAAGGATTCATCAGAGCCAGGAGTTT TCCC

CAATATTGAGTTGGCTGTCTCTGCTGCAAGACCTGGAGATACTATTCTGATTGCAGC AGGGG

GAAGTCATGTTGCCTCTAATATTCAGATAAAGAAACCACTTTGCCTGATTGGTGGAG GTGAA

CTTCCAGACGAGACAATGCTTCTCTGTTCACGAGGTTCAGACAGTGCCCTGGAGTTC CTTTC

CACCTGCAAACTGTCGAATCTAACTGTGAAAGCGGAGCTTGGATGCTGTCTGCTTCA TAGGA

GCGGAAGGCTGATTATCGACGGTTGTATTCTCCAATGCGAGACAGACCCTTTAGACT ACCTC

TCGTGCCCAATTGTGAGCACAGCTACAGGCAGCAAGGTCGTTTCCTCTCCTAATGGG TGTC

ATGGCGATGGTGTTTCGGTCTCTCGGACACGAATTGAAGGTGGTGCCAAAGCCGTAT TGAC

TAGTGGGGACCTGGCATTGCAGCGTGTTCGGGTTATATGCGCTCGTACTTCTATGTT CTTCT

GGTTCGACGTCGAGTGTCCCTCTTGACTCGATATCTTTGTGCTGTTGTCTGTAGTAT ATATCA

GTACCAGTTAGTTTTACTTTTTAAAGATGTTAATGAATATTGCTGTGATGGTGTGGA TACTGT

GGAATTTTCATCGTATCCTGTCATCCAAATCCTTATTTTCTTTTGAGATAATTAACC AATAAAA

AAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

56 CGCCCTCGATCTTGCAAGACCAAAAAAACACAGTGAGTCCTCCGTGCGCACCCGAAGAAC C

ACAGGATAAGATAAGCCGCCTGAATCTTCTCTTCTCCTCCCCCTTCAACCGCCCACC TCCCT

CGCCGCCTCCGCCTCCGCCGGCGATGGGCCAGTCGTCGTCCTCGACGGCCCCCGCGC TC

GGCGGCCGCGGCGCCGACCCCGACCCCGACCCCGACCCCGACGACGGCCACTCGGCG G

CCAAGTCGAAGGCCGTGATCTGGCCGGTGCTCGGGGAGGCCGCCGCCGAGGAGTGCG CC

GCCCCCGATCTCTCCCTCTCCATCTCCGATCTCCCCGACGAGTGCCTGGCCTGCGTC TTCC

AGTACCTAGGCTCCGGCGACCGGGCCCGGTGCTCCCTCGTGTGCCGCCGCTGGCTCG CG

GTCGAGGGCCAGAGCCGCCAGAGGCTCGCCCTCCACGCCCAGTCGGAGCTGCTGGAA GC

GGTCCCGGCGCTGTTCGCGCGGTTCGACTCGGTCTCGAAGCTCGCGCTCAAGTGCGA CCG

CAAGGCGCTGAGCATCGGCGACGACGCGCTCGTGCTGATCTCGCTCAAGTGCAGGAA CCT

CACGCGCCTCAAGCTGCGGGGCTGCCGCGCGCTCACGGACACGGGGATCGCGGTCTT CA

CGAGCAATTGCCGGGGGCTGAGGAAGCTCTCGTGCGGATCCTGTGCGTTCGGAGCCA AAG

GCTTGAACGCCGTGATTGATCACTGCGCCTCCCTCGAAGAGTTATCTGTGAAGCGGC TCCG

GAGTCCCACTGAAGGTGCTGCGGCGGAGCCGATTGGGCCTGGTGCGGCTGCCGCCTC CC

TCAAAACGATTTGCTTGAAGGAGCTTTACAACGGACAGGGCTTCGGTCCGCTGATCA TCGG

CTCGAAGAATTTGAGGACGTTGAAGCTGGTGAAATGTTACGGAGATTGGGACACGGT GCTC

CAAGTTATGGTGGAGAGGGTCGCAAAATTAGTGGAGATCCATCTGGAGAGGATCCAG GTAA

GCGATTTTGGCATTGCCTCGCTATCTAATTGCTCGGATCTCGAGATACTGCATCTGT TAAAG

ACACCGCACTGCACGAACTTAGGGCTCATATCGGTTGCCGAACGTTGTACGTTGTTG AGGA

AGCTCCATATTGATGGATTGAAGCTGAACCGCATTGGCGACGATGGTTTGATTGCTG TCGCA

AAGCGTTGCCCTAATTTGCGAGAACTTGTTCTTATCGGCGTCAATCCTACGGAGTTG AGCTT

GGATTTGCTAGGATCTAACTGCCTCACGTTGGAGAGACTGGCGTTTTGCGGTAGCGA TACG

GTTGGAGACGCTGAGATTATGTGCATCGCGGCTAGGTGTGTGGCGCTCAAGAAGCTT TGCA

TCAAGAATTGCCCAGTTTCGGACGAAGGAATGAAGGCATTAGCCTCTGGTTGCCCTA ACTTG

GTGAAACTGAAGGTTAAGAAGTGTGGTGGAGTGACTTCTGAGGGTGCAGCTTGGTTA AGAA

TGAGAAGGGGATCGCTTGCGTTGAATTTGGACTCCAGTGACCAAGAACAGATAGACG CATT

CGCCAGTGATGGTGGAGGAGAAGAAAATCATGTGGAGTTTCCTCCCGTACCTAGCCA AACA

GCCGGCGCTAATATTGCATCATCGAGCGGCACCAGTCGGTCATCTTCCTTTAAATCG AGATT

GGGCAGTTTGAGAGGAAAGAGTTTGATGGCATGCACGTTCAGAAGATGGTCAAGTGG CAGT

AAAGATTCCTAAAAGCCAAGATCTTAGGGGAATCTCTGAACAGCCAGGGTAAACCAA TGACT

GTCCCTCGGCGCATCAAATTTGAATTGTTGACTTTATGGGTCTGAAGGTTTCGAACT TTGAT

CTTCAGATGATCAGCTTCGTGCCATCACCGATTGTTGTCCTAACATGCCCAAACCTG TTTTAA

TTGGTGTCGGTCCTAAAAAAAATCGTGCTTGAGTTTGCTGGAATTAAATTCCCTGAG TTTAGA

GTGGTTTTTAGCAATCAATGGTTAGGGATACTATTCCCTTCGCTAAATGTACAGCTT TAGAGA

AACTTTGTTCGGAGAATTTCCCCATTTCGATTAGGGGTAGAAGCCCTAGTCGGCTGT TGCCC

GAACTTGCTGATGGCGATGCTCAGAAGGTATGTACTGTTTGTGGAGTGACTAGTGAG ATGC

AGTTTGTGAGGAAAGCTCGTGTTTGAAATTGATGCTTTAAATTGGAGGGAAAAAAAA AA

57 CGTGAACGTCTTGCGCTCGGTTCTTGAGCTCGTTCTTGAGAGCTGAACGGAGACGATGGG C

GAGGAATCGTTCATATACAGCTTCGTGGCGAGAGGGACGATGATCTTGGCGGAGTAC ACGG

AGTTCACGGGCAACTTCCCGGCCATAGCCGCTCAGTGCCTCCAGAAACTCCCTTCCT CCAA

CAACAAGTTCACCTACTCCTGCGATCACCACACCTTCAATTTCCTCCTCGAAGATGG CTACG

CTTATTGTGTTGTCGCCAAAGAATCAGTGGCCAAGCAAATCTCCATTGCATTTTTGG AGCGT

GTAAAAGTTGACTTTAAGAAAAGATATGGTGGCGGCAAAGCAGATACAGCTGTTGCC AAAAG

TCTGAATAAGGAGTTCGGGCCAATTATGAAGGAGCACATGAAGTACATTATTGAACA TGCTG

AAGAGATCGATAAGCTCATAAAAGTGAAGGCTCAAGTTTCAGAAGTTAAAAGCATAA TGCTG

GAGAATATTGACAAGGCGATCGATAGAGGGGAGAACCTGACCATTCTAGCCGACAAA ACAG

AGAATCTGCGTGATCAGGCTCAAGCATACAAGAAACAAGGGACACAAATCCGGCGAA AGAT

GTGGTACCAGAACATGAAAATCAAGCTGGTCGTGTTTGGTATCTTATTATTTCTGAT CCTTGT

AATTTGGCTTTCAATTTGTCATGGATTTGATTGCTCCAACTAGTATATTATCATCAC ATGGAG

AAAGGTTCAGCTTCAATTAGAGAGAGAAGAGAGAGAGAGATCTTGTAACTATACTGG CGGA

GAAATGTATCATTTGTTGTTACTTGGGACTGAAAAAAAAAA

IAbLb 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

58 GCATCAAAATTGACATCGCCTCTCCTCTAATGCCTCGGTCGTCTCTCTTCTCTTCCATTT CGC

CCTCGTTCTCCACGGCCGTTCCAATCCGACCTCGCCGGAATCTTTGAATTTCCTTTT ATTGTT

TCCGATCGAGGGGGGTTTCGGCCGGCGGGAGGAGCTGCGAAGATTTCCCTCGCGCGG CG

GATGGCGGGCGGGTACAGGGCCGACGACGATTACGATTACCTGTTCAAGGTGGTGCT GAT

CGGGGACTCCGGCGTCGGCAAGTCCAATCTGCTGTCCAGATTCACGCGCAACGAGTT CAG

CTTGGAGTCCAAGTCCACGATCGGCGTCGAATTCGCCACTCGCAGCATCCGCGTCGA TGAC

AAGGTCGTGAAGGCCCAGATTTGGGACACCGCCGGCCAAGAGAGGTACCGAGCAATC ACT

AGTGCATATTACCGAGGTGCTGTTGGCGCATTGCTTGTCTATGATGTAACTCGTCAT GTCAC

ATTCGAGAACGTGGAGAGATGGTTGAAGGAGCTGCGGGATCACACCGACTCTAACAT TGTT

ATAATGCTTGTGGGGAATAAGGCTGATTTGCGACATTTACGTGCTGTTTCTACTGAA GATGC

CACGGCATTTGCGGAAAAGGAAAATACCTTCTTTATGGAGACCTCTGCGCTCGAGTC TATGA

ACGTTGAGAATGCGTTCACTGAAGTGCTCACCCAAATACATCGAGTAGTCAGTAGGA AAGC

CCTTGAGGCTGGGAATGACCCTGGAGCTCTTCCTAAAGGACAAACCATTAACGTTGG ATCA

AAGGATGATGTCTCAGAAGTTAAAAAGGTCGGTTGCTGCTCTTCTTGAGGATTTACC CGTCA

AACATTTGAAGGAAATGAAATTTTCTCCAGTAGTCTCATGTGTCCAGATGCTTTAGT TTCTCT

ACTCTCTTTGGTTTTCAGTTTTCTACTTCATACTTGTTGTACTCTCACTTGTATAAT TCTTTCCT

TTTCTCTGGCTCTTCCCTTCTTTTTTGTCTTGGGGTTGTGATTGCTCTAAATTATTG GGACAA

GCTCGAAAATT

59 GCATCTCCCACCCAACCCCTACTCTCTCTCTCTCTCTCTATCTCTATATCGTCCTGTCAA GAA

GAAGGAAGAAGACGAAGAAGGAAGGTGAACAAGAAGCAAGAAGAAGATGCAGCAGTA GAA

AGGTGAGATCTCGATCTCGCACCGATGCTCTCGAATCGAACCTGTTCCTCCCCGATC CCCC

CGCATCGATTCGCCTGAACCACAAAAGAGTTCGCATCCTTTTCCCTCCTTCGAGGCG TAGA

GCAGTTAGGGCCTTGAGCATTCATGGCGGAACTCGCGGGCGATCTGCCCGGCGAGCT GGT

GACCGAGATCCTGGACCGCCTCCCGGTCGAGTCGCTGCTCCGGTGCCGCTCCGTCTC CAA

GCGGTGGCGCGGCATCATCGACAGCCGGGAGTTCGTCCGCTCCCACCTCGCCCGCTC CTT

CGAGTCCACCGCCAACCTCACCCTCTTCTTCCGCCACTCCTCCAGCCTCTACTGCAT CGAC

CTCACCTCCCTCCTCCGCCACGGCGGCGTCGCCGAGATGAACTACCCGCTCATGTGC TACA

GCGACCAGATCCGCGTCCTCGGCTCCTGCAACGGCCTGCTCTGCATCTCCAACGCCG CCG

ACGACGTCGTCGTTTGGAACCCCGCCACGCGGAAGCACAAGTTCCTGCCGTACTCCG CCG

TCGAGGTGCGGCGCTCCTCGGTTTTCTCCGTCTGCGTCTACGGGTTCGGGTACGACG AGA

GGCGAGACGATTACGTGCTGCTCAGGCTCGTCCAGCTCGTGACGGAGCCGATCGAGT CGG

AAGTTAGTATCTACAGCTTGAAGGATAACGCTTGGAGGCGGCTCAAGGACATGCCGT ACTC

CCTCGTTTATCCCCGCAAGATGGGGGTTTTCGTGTGCGGCCATCTGCACTGGATAAT GACT

CGGGAGCTGGTGTCGGATTCGGCGAATCTGCTGGTGGCTTTCGATTTTCGAATTGAG GATT

TTAAGGTGGTGGACCAGCCTGAAGGTATCGATAATAAGCTTGACATGGATTTGTCCG TCCTG

GGAGGGTGTCTCTGCCTTAGCATTAACGGGAACCACATGGGTGTCCATGTGTGGATT ATGA

AAGAGTATGGATTGAGAGATTCATGGACTAAGTTGTTCTCGATACCGCAATCTGAAG TTGCC

AGACCTCTTGGGTTTGTCCGGCCGTTGGCTTACGCCAGCAATGGTCGTCAAGTTTTG GTAA

GACAGGACAGTAAGAATCTCATTTTGTATGATCTAGAGACTAAGGGCATGGAGAGGG TTGAT

ATAAATGGCATGCCAAATTCCTTTGAAGCAGAAATTTGTTTGAGAACCCTTGTTTCG GTCGAT

GATTATGGAGGATACACCAAGAAGAAGCAGCAAGAAGCGGAAGAGATTGAGAATAGG ACCA

AGAGGGATGACTTCCTCTCGGTGGGCTTCAAGCTTGTTCTCTAATCGAGACATAGTT GTGCA

AGGGGGGTGTCACAAACTACTCAGCGAAGGAAATGCAGTAGGAGAAGTTAAGTTTTT TGCC

TCAGTATTTAGATTCATGGCTCAACTTTCGACAATATGGACCAATGTATCATTGGGA AAGGTT

TGGCAAAAAAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

60 CTTCTTCTTCTTCTTCTTCTTTCTCCTCTCTATGGCGGACACCGCAACTCGAGCGATTCC TCC

GAGAATGGAGTTCTCCGACGAGGCTGCGGCCGGCGGAGCTGCGGCGCCGGCGGCTGC GG

CGGCGGCGGCGGAGGAGGAGGAGGAGGAAGAGGAGGCGCCGTCGCCGGCGGCGGAGA T

CAGCGAGGTCGAGAAGAGCAAGATCGGCATCATGCGGGCCGTCGTGGAGCGGGACGA CC

CTTCCGCCAAGGATGTCGATGATTTTATGATACGGAGGTTTCTGCGAGCTCGGGATC TAGAT

ATAGAGAAGGCTTCCAAGCTATTTCTGAAGTACCTGAGCTGGAGACGGTCTTTCGTC CCCAA

TGGGGTCATATCGGCATCAGAAGTTCCAAATAACCTTGCTCAGCGGAAGTTGTTTAT GCAAG

GTCTTGACAAAAAGGGACGGCCTATAATAGTTGTGTACGGGGGTAGACATAATCCTT CCAAA

GGAAGTCTCGAGGAGTTCAAGCGTATGATACTTCTCTGATTCTTCCGGATTTTCTTC TAATCA

ATATGAATTTATCGCTTCATGCAAGACTTACCATCATCATATTATTGAAAAGAAATT TAGGCA

GAAAAATACTGAATTTGGCTAAAGTTGAGTTGTTTTTTACTGTGGCGAAGGTTTTGT GGTCTA

CACTCTTGACAAAATATGTTCCAGGTAACTCTTCTCCTTATTAAGACTCTGCACATC ACGGAA

ATCTAAAAACATTGCAAACTGAGGATTCTTCCAAAAATGAAATCCTTCAGAAGCATT CTGGTT

AAGGTGTCTATCTTGTGAGGCACAAAAATTGCACGTGTCACCTAATTGCATGATTGG AAAAG

AATGGCCATATTAGTTGCAAATGAAGCCCTTGAAGACTATATCTAGAGCCACCCTCC TCAAT

GGGAAGTATCGGAAAGTTTTTACCTGGTCCCTTATTGGTTTCTCAATTCCCAGTTTC TTAAGA

ACTGTGATCAACCCAAGTCTTTCTTTTGAATTCGCTATCCAGTGTTGGTCAAATTTT AGCCAA

TAATTTAAGTTGTTTCTTGGGTGTTGATCTTTCAGAATGCCTGGAGGGCAGGAGAAG TTTAT

GGGCATAGCAGATCTCGAAGGATGGGGATACAAAAGCAGCGACATTCGTGGATACTT AGCA

GCATTGTCAATCTTGCAGGACTGCTATCCGGAGAGGCTGGGCAAGCTCTTTCTTATT CATGT

GCCTTACATATTTATGACTGCATGGAAGATGGTTTACCCATTCATCGACCCTAAGAC GAAAA

AGAAGATTGTTTTTGTCGATAACAAAAAACTGAGAACTACTCTGCTCGGGGACATCG ATGAA

AGCCAGCTCCCGGATGTATATGGAGGCAGGTTGCCACTAGTTGCCATTCAAGACAGC TAAA

TTCTGCTCAMTTACMGMTTTTCTCCTCATTTCTTTTCTGGCCGTGGGTCTATATTGT AGAA

TATMTGMGATATMTTTGATAAAATGCGGAACAACAGCCAMTATTTCATGGCTGMCTC T

CTTGATAAAAAAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

61 AGAACAAGACCCCGTCCCTCACTACTACTGCACGCGCGACGCGACGGGAGATATGGCTGC

TCGGCTCTTTTCAAGCCTCCTCTCTCGCTCCTCCTCCGCCGCCTCCTCCTCCTCGTC GTCTT

CTTCTGCTCGTGCTCTGCTTTCTCGAGCGAGAAAACCGCTACTGGGAAGAGAAATCA AGAG

CTACAGCACAGCAGCTGCTATCGAGGAACCGATAAATCCAGGCGTCACTGTGAACCA TACT

CAGCTTTTCATAAATGGGCAGTATGTGGACTCAGCATCAGGAAAAACTTTTCCGACC TTTGA

CCCCAGGACCGGAGAAGTGATTGCTCATGTTGCTGAAGGCGAGGCTGAAGATATAAA CCGA

GCTGTAGCTGCTGCTCGCAAGGCATTCGATGAGGGACCATGGCCTAGAATGACTGCT TATG

AAAGGGCAAATGTACTATTTCGCTTTGCCGATTTGCTTGAAAAGCATAATGATGAGA TTGCA

GCACTCGAGACTTGGGATAATGGGAAGCCATATGAACAGGCTGCCAAAATTGAGCTT CCAA

TGATCGTCCGTCAAATTCGATATTATGCAGGTTGGGCTGATAAGATTCACGGTCTCA CAGTT

CCAGCTGACGGGCAGTATCATGTCCAAACCTTGCATGAGCCAATTGGAGTTGCAGGT CAGA

TTATTCCGTGGAATTTCCCTCTTCTGATGTATGCTTGGAAGGTGGGACCTGCCTTAG CCACA

GGCAACACCGTTGTACTGAAGACGGCAGAGCAGACACCACTTTCTGCTTTATATGCA ACCAA

GCTCTTGCATGAGGCTGGTCTCCCCCCTGGAGTGTTGAATGTGGTTTCTGGTTTTGG TCCAA

CTGCAGGCGCAGCTCTTTCCAGTCATATGGATGTTGATAAGCTTGCTTTCACAGGAT CAACC

GACACAGGGAAAATCGTACTTGAGTTGGCAGCAAAAAGCAATCTTAAGCCAGTGACT TTGGA

GCTTGGAGGGAAATCCCCTTTTATTGTATGTGAGGATGCTGATGTTGACAAGGCTGT TGAGC

TAGCCCATTTTGCTCTTTTCTTCAATCAGGGTCAATGCTGCTGTGCTGGATCTCGTA CATATG

TACATGAAAGCATATATGAAGAATTTGTAGAAAAGGCAAAGGCACGGGCAACAGTGC GTAGT

GTGGGTGATCCGTTCAAAAGTGGCATCGAACAAGGTCCTCAGGTAAGTTAGCCGATT CTCC

TGTATGAGGAAATTTGAATGGATAAGATTGATATCTTGCGAATGGAAGTAAACTCCT GCTCTT

ATGACTCTTTTGTCAAATGTAATTGACAAATTTGATATTTTTGTCGATTTCACATAA ATTTACT

GGATGGAAATTGAAATGCAACTGAAATAAATCCTTGATAAATGGAGCTAGTCGTTTG ACTAG

TACCTGTATGTAGATCTAATGGAAGCTACAGAGTTCTGAGCGTTCTTTATCTTTACC TCACAT

CAGATAGACTCGGAGCAGTTTCAGAAGATTTTGAGGTACATAAGATCTGGAGTAGAA GGTG

GAGCAACTCTTGAAACAGGAGGAGAAAGATTTGGAACCAAGGGACACTACATTCAGC CAAC

TGTATTCTCAAATGTTAAGGACGATATGTTGATCGCTAAGGACGAGATTTTTGGTCC CGTGC

AGACCATTTTGAAATTCAAGTGAGTATAAGACCATCTCCTCAAGCTCATTACTAGAG CGGCTT

TCCGGTTAGGATGCATGGTACGATTGTCTGTTGACATGGTGACATCTTTGTCATGTT TAATTG

CAGGGACCTCAAGGAGGTGATTCAAAGGGCAAACAACTCACGCTACGGGCTGGCAGC TGG

AGTCTTCACCCAGAACATAGACACGGCGAATACCTTGACCCGCGCTTTAAAAGTTGG AACA

GTTTGGGTTAACTGTTTTGATGTCTTTGATGCGGCTATTCCATTTGGCGGGTACAAA ATGAG

TGGCCATGGAAGGGAAAAGGGCGTGTACTCTCTGAGCAATTACTTGCAGGTCAAAGC TGTG

GTCACTTCTTTGAAGAATCCAGCATGGCTCTAAGCTGAAGTTTGCTTTCATCTTTGG ATTTTT

CGACCCTTGATATTTTTTAATAATAAGGGAAGTAACAGATACTGGAGTTCAAATTAT TATCGT

GACAGTTGTGATGGGAGTTTTGAGGCGGTGACGACGACGATTGTAGGACGCTGGTGA AATT

GCTTCTGTAGCAAACAGTGCCGTGAAGAATTCACTTTTTGAGTGTTCACGATCAAAT TGTGC

TACTATACATTATTGATGTTACTTTTGCCATCTTCCAGGCTTG

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

62 GCATGAGTTCCTCCTCCTCCTCCGGCGGCGGCGGCGGCGGCGCGAAGCTCCCTCACGAC

GTCGCCGTCGAGATCCTGAAGCGGTTGCCGGCGAGATCCCTCCTCCGATTTAGGTGC GTCT

GCCGATCGTGGCGTTCCGCCATCGACGACCCTCGTTTCGTGGCCCTCCACTGGAGCC ACT

CCGCCCTCCACGCCTCCAGTCGGCATCTCGCGTGTCTAGACTGCGGCGACGACGCCG TCC

AGAACCGGTGCTCTCTGTTCCCCAACGCCCCTCTCGCCCTGCCTCCTCCCCCGTCGC AAAT

CGAAATCCCGTTCGTTGCTCCTCCCAACCGTTACGCCCTCGTCGGTTCGTGTAACGG TTTG

ATCTGCGTCTCGGAGAGTTCCAGTGACGGCACTGAGCGGGCGCTGTATTTTTGGAAT CTAT

TCACCAGGAAGCATAAGGCGGTTCGGCTCCCCCGTCCGGAGCGGATGCCACCCTTCT CCG

TGGGGGGCGCTCATGTAGTTCTGGGGTTTTGTTTCGATGCGAAGTCTAATGACTATC GTGTT

GTCAGGATTATCCGATACCTAGGTATTCGCCGTCGACGCTTCCGCAATAAGAAGCCT CGAG

TCGAGGTTTATTCGTTCCGTACAGATTCATGGAAGACCTTGGAATGTGAGGTTCCTC TTCTC

TGTGACAGTGCGGTCTTCTTGAATGGGAACCTGCACTGGTATTCTTTCAATGGGGAG GGGG

ATGGATACGGATCCATAGTCTTGTTCAATGTCGCAGATGAGGTGTTTGATGAAATAG CTCTG

CCGGAAGGGATCAGTCCCCATTTTGTGTTGTCCGTGACGGTATTGAATGAATCGCTG GCTG

TGTTCTTTAGTCATAGGGAGGCTTGTTTCGTTTGGGTTATGAAAGACTACGGCGTGC CAGAG

TCTTGGAGTAAGCTGTATACTTTCGAGGTTACGGAACCGGTAACAGGATTTGATGGC TTTAC

ATGGAATGGCGAGCTTCTTATGGAAATAAATTGTGAAGAACGAGTTTCTTGGAATCC GATCA

CAGCACAACTCTCAATTCTTCCATTGTCGGCGAGATACAAATTGGTCCCCGTTGTAG AGAGC

CTCGTTCCACCTTAGATATGACTCGATTGCTGCTATATCGTCAGGTGCAAGGTGCTG GAGCT

CTTCTTTATTAACAGGAATTCTGGTGATTGGCAATGCAAGTACAGCTGGCTCTAACA AAAATG

GGGGAGTGGCAAAGGACAGCAGAAAGTGATGTTGAAGTTTCTTCGGAATATAGTTTA CGTG

GAAGGCAAGAAACAATCTGCTTCATGGTTAAGCTACTTCTCCCTTCGAGCATGTTCT TAGATT

GATCGATTTGTTACTTAACATCAATTTGAAGGCTATCTAGTTTCAAAAGGATACATG TCGTGC

TTATGATTATCTATATAATGTAATGTGTGAGATTTGCTTATAAAAAAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

63 CAAGCGCACTGCATTGATTTTCGAACATCGCCGGACGAGACACACACAATTCGCTCTCAT TT

TCAAAATCGATCTATCCAAAACCCTCTTTCTGTCTTTAGGCCATTTCTCCTCTTTGC CATCTC

ACAGTCTCACTCGCCTTTCATTCGACGCTCGTCGCTCTCTTTCCCCGAACGTTTGAA GAAAA

CGCGACGGTTTTTGAGGTTGTGTTGTGATGGATGCTGCACCATTGACTTCTCAGCGC CGAC

CATTTTCAGTGAAACTATGGCCCCCGAGCAAAAATACTCGTGAAACACTTGTAGAAC GGATG

ACAAGGAATCTCACAAGTGAATCCATTTTCACTAGGAAGTATGGAAGTTTGAGCCCG GAAGA

AGCTGAGGAAAATGCAAAAAGAATTGAAGATGAAGCTTTTACAACTGCTAATCAACA TTATGA

AAAAGAGCCTGATGGTGATGGAGGGTCTGCAGTGCAGCTCTATGCTAAGGAATGCAG TAAA

CTTATACTGGAAGTCCTCAAAAAAGGCCCAAAAGGCAAGGATGAAAAGCCGCCAACT TCTG

ACAGTGCTAAGGCCCCTAGAGAGACATTTTTTGATATTTCCAAGGGCCAGCGGGCCT TCATT

GAAGCAGAGGAGGCAGAAGAACTTCTGAGACCATTGAAGGAGCCTGAAAATTCTTTC ACCA

AAATATGCTTTAGCAATAGAAGCTTTGGATTAGGAGCTGCTCATGTTGCTGAACCCA TTCTG

ATTTCCCTGAAGCAACAATTGAAGGAGGTAGATTTATCTGATTTCATTGCAGGAAGG CCAGA

AACAGAAGCTCTTGAAGTCATGAGCATATTTTCAGCTGCCTTGGAGGGTAGTGTTTT GAATT

CTCTAAATCTTTCCAATAATGCTTTGGGTGAAAAAGGCGTCAGAGCATTTAGCGCAC TCCTG

AAATCACAGAGTCAATTGGAGGAGCTCTATTTAATGAATGATGGAATTTCTGAAGAA GCTGC

TCGTGCAGTATGTGAGTTGATCCCTTCCACAGAAAAACTTAGAGTTCTTCATTTTCA CAATAA

CATGACAGGAGATGAAGGGGCGATTGCTATTGCTGAGGTTGTGAAATGCTCTTCATT AATGG

AGGACTTCCGCTGCTCCTCCACAAGGATTGGCTCTGATGGAGGTGTTGCCTTATCAG AAGC

ACTTGAAAATTGCATCCATCTGAAGAAACTTGATTTGAGGGACAATATGTTTGGTGT AGATGC

TGGAGTTGCTTTGAGTAAAGCTCTTTCCAAGCACACTAATTTGACTGAGGTTTACTT GAGTTA

CCTGAATTTGGAAGATGAGGGGGCAATTGCTATAGCCAATGTTCTTAAAGAGACAGC CTCAT

CTCTTACAGTTCTAGATATGGCTGGCAATGACATAACAGCGGAAGCAGCTCCAACTT TATCT

GCTTGTATAGCTGCAAAGAATCTTCTCACCAAATTGAACTTGGCTGAGAATGAGCTC AAGGA

TGAAGGTGCTATTCAGATTGGCAAAGCATTGCAAGAAGGCCATGAGCAGTTGACGGA AGTT

GATTTGAACACCAACTCGATCAGAAGGGCTGGAGCTCGATTCTTGGCCCAGGTTGTG GTGC

AGAAGCCTGGTTTCAAGTTGCTCAACATCGATGGAAATTTCATTTCGGAAGATGGGA TTGAT

GAGGTCAAGAGTATATTCAAGAAATCCCCTGAAATGCTGGCTTCCCTAGATGAGAAT GACCC

TGAAGGAGGTGATGAAGATGAAGAGGACGAGGAAGGTGAAGCGGAAGGTGAAGCTGA TGA

AGGTGAGCTGGAGTCAAAGTTGAAGAATCTTGAAGTAGGTGAAGAGTAGGATATGTT CTTTC

TAGTTTAAGGTAATTTGAATTGGCTGTCCAAGTTAGTTCAGGAACAGCTTTAATAGC CAGGAA

CATTTTTGCTGAATTTTTAGCTCATTACATCGTCGAGGCTCATGAACCATGAGCAGG ATAATC

GTAGCTCCTAGAGATGAGCATTTTTTTTACTCAGGAGGACGACCTTGGAGGAGCTGT TCGTA

GGGTACTCATTTTACAGTGTACCGGGTAATCTTGTCGTATGAAGGGATTACCAGAAC TTCCG

TTCTAGTTACTAGCTACTAGCTACTAGCTAGTGAATTGTTTTAATGCGCTTTCTTCT CTCCTA

GCTGATTTTATTCATTAAAAAAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

64 GCTCTCTCTCCCTCCCTCCTTCCCTCTGATGGCACTCGTCCGCGAACGCCGGCAGCTCAA C

CTCCGCCTCCCGCTGACGGATCTCCCCAACCGCCGCCCGCTCTTCCCGCCGCCCCTC TCC

CTCCCCCTCCCTCCCTCCGCCGCCGCCGCCGCCTCCGCCACCGCCGCCGCCGGCTCC GG

CGCCGCCGCGACCTCCCTGTCCGACCTCGAGAGCCTCGGCGTCCTCGGCCACGGGAA CG

GCGGCACCGTCTACAAGGTCCGCCACCGGCGCACCTCCGCCGTCTACGCCCTCAAGG TCG

TCCACGCCGGCTGCGACGCCACCGTCCGCCGCCAGGTCCTCCGCGAGATGGAGATCC TCC

GCCGCACGGACTCGCCGCACGTGGTCCGGTGCCACGGCATCTTCGAGAAGCCGAACG GC

GACATCGCGATCCTGATGGAGAACATGGACGCCGGCAGCCTCCAGACGCTCCTGGAG GCC

TCCGGGACCTTCTCGGAGAAGCAACTCGCCGCCGTCGCCCGCCACGTGCTGAACGGG CTC

CACTACCTCCACTCCCTCAAGATCATCCACCGCGACATCAAGCCGTCGAACCTGCTC GTGA

ACTCGGCGATGGAGGTCAAGATCGCCGACTTCGGGGTGAGCAAGATCATGTGCCGGA CCC

TCGACGCGTGCAACTCCTACGTCGGCACGTGCGCGTACATGAGCCCCGAGCGGTTCG ACC

CGGACAGCTACGGCGGCAACTACGACGGCTACGCCGGCGACATCTGGAGCCTGGGGC TG

ACGCTGCTGGAGCTCTATCTGGGTCACTTCCCGCTGTTGGGTCCCGGCCAGAGGCCC GAC

TGGGCGACGCTGATGTGCGCGATCTGCTTCGGGGAGCCGCCGAAGTCGCCCGACGGG TC

GTCGGAGGAGTTCCGGAGCTTCGTCGAGTGCTGCCTGCAGAAGGAGTCGAGCAAGCG GTG

GTCGGTGGCGGAGCTGCTGAACCACCCTTTCATAGCCGGCGGTAAAGATCCGGCGGG ATC

CTTGTGAGGTGGAAGCACGCGGGTCGGGTTGAGGCAAAGTATTTTACCGCTGGAAAA CCC

GGAAGTCGAGGCGGGCGCACGCAGAACGGGCCCGCCCGGGACAAATCAAGTACGGGT CG

GGTCGAGATTCGCTTCGCGATGAGTTTTTGTACATATAGGGCGGACTTCGGGTCGCA AATT

CGGGCGCTCTCTGTTTCTTTTTTCTTTTTCAATGTCCTCTTTAGGATGCTTCGGGCA GTGAAA

TTGCTGTTCGAGAACTAATGAAGGACCCTTCTTGACTAGTTCAAAAAAAAAAAA

65 GCGGAAAACCCGAATCCCGGGAAAAAGAAACAAGCCTCGAGATCACTGATCAGAGAGAGA A

GGAGGGAGATGGTGAGCGCAGCGCAGGCGGCGGGCGGGAGCCTGAGCCTGAGCCTGA G

CCTGCGCGATCGCGAGATCCTGACCTCGGTGAACTCGGTGGCGTCGAGCTTCTCGCT CCT

CGGCTCGGGCTTCATCGTCCTCTGCTACCTCCTCTTCAAGGAGCTCCGCAAGTTCTC CTTCA

AGCTCGTCTTCTACCTCGCCCTCTCCGATATGCTTTGCAGTTTCTTCAACATAATTG GTGATC

CATCCATAGGATTCTTCTGTTATGCTCAGGGTTATACCACCCACTTCTTTTGTGTGG CATCCT

TTCTTTGGACAACAGTGATTGCATTTACTCTTCACCGGACTGTCGTTAGACACAAGA CTGAT

GTTGAAGATTTGGAGGCTATGTTTCACTTGTATGTATGGGGCACATCCGTGGTTATG ACCAT

CATACGCTCTATTGGCAATGATCACAGACATTTGGGTGCATGGTGCTGGTCACAAAC AGGG

CGCACAGGAAAGGCAGTTCACTTCATTACGTTTTATGCGCCACTCTGGGGAGCAATC CTTTA

TAACGGTTTTTCATACTTTCAAGTGATACGCATGTTAAACAATGCCACACGTATGGC CGTTG

GCATGTCAGATCGAGCATACCACTTAGATGCAAGACCTGATATGAAGGCTTTGAACA GGTG

GGGATACTACCCGCTCATTCTGATAGGATCATGGACTTTTGGTACAATCAATCGCAT ACATG

ACTTCATTGAACCTGGACATAAGATTTTTTGGCTGTCTCTTCTTGATGTTGGCACTG CTGCTC

TGATGGGTCTGTTCAACTCAATAGCATATGGCCTGAATTCTTCCGTGCGACGGGCGA TTCG

CGAGAGATTGGATCTAGTAACGTGGCCGGAGACGATTAGGCCATGGTTGCCTAACAG TTCA

AGGATCAGACACCAACAGCAAGAGAGTGAACTAGTGTCACTGAAAAGCCAAGATCCG CACT

GACGATTCCAAGATTATGCCCATCTTCTTCGACGAGTGGTCGAGTATAGCCATGGAG CTACT

GGTTTTGAAACCCTCATCAGACTGATCCAAAGTTCTGGTAGATGCTCACGGGATGGA CCTTC

TTCTGTCATTTTAATGAAACAGCCGGTAATCTTTTCGCGACAAAGGGGTAGCGTTGC CCATC

TGCAACTGGTAGCTGCAATCTTGTACATTAGGAAGGTAAAAAGCCCTTTTTGCGATT GTGAT

TCCTTCCTCCGCTGGGGACTCGGGTGCCGGCTCCCCATTTTGTAGGTCGAATTGTAC AACA

ATCTCTCGTCTCCCTAATATCCGTTACGATCATATTCTTTCGACAATAGACTGATCC CTGACT

GCTTTACGTTGTTTCAAAAAAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

66 GCTCATATCGMCCTGTTCCTTCTGGATCATGTGAATCGATTGACCAAAAGAGGAGCGTTT T

CTCATCGTCTTCCTCTTTGTCGCAGTTTGTCTCGAGCTGTAAGGAGATTCGCCACAA TGTAG

CCGTCACGGCTCGTCTCGAACTGTAAGGAGGCGAGATTCGGAAGTACTCTGGGAAAT GGC

GGGCCTTTCGGACGATCTGATCACCAAGATACTGGACCGATTCCCGAAGGAATCGCT GATC

CCCTTCAGGTGCGTGTCCAAACAGTGGCGTCGCTTGATAGACGACCGTTTCTTCAGG AAGT

CGCTCCTCTACCTCGTCCCCATGTATTCCTCGAGTCTCTACCGTATCGGTCTGCGTC GCCTG

GGTGACTTGGTGGAGATTGAGAACCCTTTCGAGTCGGAACAGATCGTGTTGTTGGGG TCTT

GCCGTGGCTTCCTTTGCATTTATAATGAGATCGACGGCCAGATTGCTATATGGAATC CGTCC

ACTAGGAGTTGTCAGCTCTTGCCACCTGCAGATGCTGAGATAGCCCATAGATTGGGT CCCC

CTGCTTGCGTTTATGGATTTGGATATGACTATTGGAATGATGAGTTCGTGTTGTTGA GGCTG

GTTCAGACCATGGAAGATCCAATTCTATCAGTTAGCATCTATAGATCAAGAGGTAGC GTGTG

GAGGCGGCTCCAGGGGATACCACCATACTCTTTGGTTGAACCGCGCACAATGGGGGT TTTC

TTGCGCGGCCGTCTGCACTGGATAATGAGACGCGACCCGATGCAGAACTCGGCAATA GTTC

TGGTGGCTTTTGATATTCATACTGAAAACTCCGTGGAGGTACAACAGCTTAATTTTA TTGACA

ATAGGCTTCCAATGTATTTGGCCATCCTGGAAGGGGGTCTTTGCCTTATTATTAATG ATGAG

CGAGGGGGTGTCAGTGCGTGGATTGCAAGTGAATATGGATCGGAAGAGTCATGGGCT AGG

CTGTTCTCGATAGCTGACTACTCGATGGGTCGGGTACTTCTCCAGCCACTGGCTTAC TCCCA

GAACGGTCGTCAAGTTTTGCTCCTGTACCGTGAGACTCTCGTTTGGTACGATTTAGA TACCG

GTGACGTTGAGAATATAAACAGCATGCTAAGCATCTCCAATACACCTATTGTTGGAG ACTAC

TTAGGGTCTCGTCGTCGGAGACTACAAGGTGCGTGGAGGCAGCTCGAGGGTATGTCG TAC

TCTCTGGGTAATGCGTGCAAAAGGGGGATTTTCCTGCATGGCCGTCTGCACTGGATA ATGA

CTCTCCAGCTGGTGCTGAATTCGACAAAAGTGTTAGTGGCTTTTGATATTCGTTCAG ACAAA

TTTATGGAGGTGAGCGAGCTTAATTTTATAGATAATAGGCTCAACATGGATTTGACC CTCTTA

GGAGGGTGTCTTTGCCTTATCATTTATGGTGAGCAAAGGGGTGTCCATGCGTGGATT ATGA

GGGAATATGGATTAMCAGACCATGGTATATGTTGTTCTCGATGCCTGGCCACTCAAG GCC

GCTATTGGCTTACTCCCAGMCGGTCGTCMGTTTTGGTGGCAGTGGGCGGTMGACTCT C

GTTTGGTACGATAGAGTCTGGTACGATTTACATACTGGGGGTGTCMGMGTTCGGTMM G

GGGCATGCCMGTTCCTATGMGCAGAAATTTATTTGCGMCCCTTGTTCCGGTCGGTAA GC

CGCCGATATGAGGAGGGACGACTTCTGAGCTAATGACTTGTTTGGAGGATCGTCGAT GATC

TGCATCGTAATCATCCAAAGTGAAGTCAMTCTGATGTAATCTGGAGTGTACTCTGMT GCG

TGTTGTGGTTTGMTGTACTTAGATGCCAGTAGTTTCTAGCCTGTTGCATCCGCTTAT TTGCT

ATATTMCGTATATTCAGCAAAAAAAAAA

67 GGTGTTTATCGCGTGCTGGAAACMCGMGGMGGMCGMGGMGCACTTCGCGTGCTGA

GATTACTTACTCTCTTCGGCGGCGTCCCGGGCGAGAGCTCCGATTCGGTTCGATTCG ATTC

GATTTGCGATGGCCGGAGGAGMGCCTTCTCCTCGMTCCTCCGCCGCCCMGCCGGCGA

TTCTCGGGMCMCAGCMGACCATCMTGCGMGCTCGTGTTGCTGGGGGACATGGGTGC

CGGCMGTCCAGCCTGGTCTTGCGCTTCGTCAAGGACCAGTTCTTTGATTTTCAGGMT CM

CTATAGGAGCAGCATTCTTCTCGCGGACAGTGGGTGTCMTGATGCATCAGTGMGTTT GA

GATATGGGATACTGCAGGTCAGGAMGGTACCACAGCTTGGCTCCTATGTACTACAGA GGC

GCTGCTGCAGCTATTGTTGTCTATGACATCACTAGCACCGAGTCATTTGMCGGGCTM GM

GTGGGTGGAGGMCTTCACMGCMGGMATCCCMTTTGATMTMCACTTGCTGGAMTA

AGACTGATATGGAGGATAAMGMMGTGGCAGCTGAGGAGGCATGCATGTATGCAGAAG A

MGGCGACTCGTGTTCATAGAMCATCTGCTMGACTGCCACTMTGTTAGCAAACTGTTT T

ATGAMTAGCAMGAGGTTGCCTAGAGTTCAGGCTATGCAGMTTCAGCGCCAGCGGGMT

GGTTCTAGCAGATACAAGCTCTGMGAMCCCGATCTGCATCCTGTTGTTCATGAGTTC TTA

TCMCTCTCTGTCCATTCCTTTCCTTTTTCCCCTCACTTTCTATAGTTGTCTCCACTC AMGTA

CCTTGATCTTTTAGTTCTTGATGTATATGMTAAMACMATCCGMCACCACTTGTGAMT T

GGAAMCCMTTGGAGTTGGGGAGTTAGTCCATTTAMCCCAGTAMTTCCTCGGTGMMA

AAAM

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

68 GGGAGAGTTCAGAGGTAAAGGAGGAAAGCAAAAAAATGGAGATTCCTATGATAGATTTGA G

TGAGCTTGATGGTAAGAACAGGAGCAAAACAATGGCACTGCTTCACCATGCTTGTGA GAAAT

GGGGCTGCTTCAAGATTAAGAACCATGGAGTTGACCCAGAACTGATGGAGAAAGTGA AGCA

TTTTGTCAACACCCACTATGAGGAGAATTTGAAGGCAAGTTTCTATGAGTCAGAMCT GCCA

AATGCTTGGAAAATGCCAATGGTGCCACATCTGATCTAGACTGGGAATGCACCTTCT TTATC

TGGCACCGCCCGAAGTCGAACATTGAGGACTTCCCGAACCTCTCGAATGATCTTCGG AAGA

CAATGGATGAGTACATTGCTCAGCTGGTTAAACTAGCAGAGAACCTCTCAGAGCTCA TGTGT

GAGAATCTTGGCCTAGGCAAGGACCACATAAAGAGGGCATTCTCAGGGAAAGATGGG CCCT

CTGTGGGGACGAAGGTGGCGAAATACCCGGAATGCCCCTATCCGGAAAAGGTAAGAG GAC

TCAGAGAGCACACTGATGCAGGTGGTATCATACTGCTGCTTCAGGATGACCAAGTCC CAGG

ACTTGAATTCCTCCATGATGACCAGTGGGTTCCAATCCCACCATCCACAAACGACAC CATCT

TCGTCAACACCGGAGACCAACTTGAGGTGCTGAGCAACGGCCGGTACAAGAGCGTCT GGC

ACCGTGTCATGGCTGTGGAGAGCGGGAGCCGGCTCTCTGTGGCCACGTTCTACAATC CCG

CCGGCGATGCGATCATCTCGCCTGCGCCGAAGCTCCTGTACCCTGAGAAGTACACTT TTGG

GGAGTACCTGAAGCTTTATGCCACTACCAAATTTCAAGAAAAAGAGCCCAGGTTTGA GTCGA

TGAAGAGTGTGATGAGCAATGGATACAATGGAGTTGTCTAAGAGCTGCCAATAACTA AATGG

ATCAGGCTCATTTGTCTCTGTTTGGATTTTGTTTTTACTTTTTCTTGCTTTGATAGA AACATGG

TCTTGTGGTTATATATGCCAGTTGTCTCTTTTACAGTGAGTTTTGTGTAACTCCTAA AGAAGA

GATGGTATAAGTCTGTCTTTATCAGCTTTCTTGGCTCTCTTTGTGCTGATGTTGAAT GGGCTC

CAATGAAAAAAAAAA

69 AATTTCCTGGGTGGCTGCATTTTCTTTACTGGGCTGCTGCTGGAGAGACAGAAGAGGAGG A

AGAATTCATGGCTACAGTTCCTCAAGAAGCGATCAATGAGCTCCAAGCTCTGATGGA TCGAG

TTGACGAGCCGTTGATGAGAACATTCGAGAACATTCATCAAGGGTATCTTAMGAAAC TTTG

GTGCGTTTTCTAAAGGCGAGAGAAGGCAATGTTGCCAAAGCCCATAAAATGTTATTG GATTG

TTTGAAGTGGCGTGTTCAAAATGAGATTGATATCATTTTGTCGAAACCAATTATCCC TGATGA

CTTGTACAGAGCTGTGCGGGATTCACAACTTATTGGATTGTCAGGTTACTCCAAGGA GGGA

CTCCCAGTATATGCTATCGGGGTTGGGCTTAGCACCTTTGACAAAGCTTCAGTTCAT TATTA

CGTGCAATCACATATTCAAATCAATGAATACAGAGACCGTGTAATTTTGCCTTCTGC ATCCAA

AAGGTACGGGCGACCTATTACCACTTGTTTGAAGGTTCTAGATATGTCCGGCCTGAG GCTTT

CAGCCCTCAGTCAGATAAAGTTGTTGACTATTATATCGACTGTTGATGACTTGAACT ACCCTG

AAAAGACGAATACCTATTACATTGTGAATGCTCCATACGTCTTTTCTGCTTGTTGGA AGGTTG

TGAAACCACTTTTGCAAGAGAGAACGAGAAAGAAAGTTCAGGTGTTGCCTGGTTGTG GACG

TGATGATCTACTAMGATAATGGATTACAGTTCCCTCCCACATTTTTGCAAGGGGGAA GGTT

CGGGTTCTGGTCGGCATACATCATACGGTCCAGAAMTTGCTACTCGTTGGACCATCC CTTT

CACCMCAGCTTTACAGCTATATCMGGAGCAATCTCAGAGACGTCMCCCATCCMCCCA T

CAMCAGGGCTCTTTTCATGTTGCGCTGCCTGAGGCCGCTGCAGMGGGACAGAGATCG CT

AAMCCATAGMTCCGAGCTACAGMGTTTGMMCGGMGTGGGATGCCTGACTCACTGG

ATGGCCTTAAMTCMTGGCGAGTGMGCCGTTGGGATCAMATGCTTCGGACGACCATTT

GCAGCGATGMTCTAACMGAGCTGATCATTGCCTTGATTCAACTACGTGAACGATGAT GTG

TGGGCCATTTCCAGTCACGCGACGTMCAGCACAGTATGGGTGGCTCTCCCTATTGTC TAT

GTTATCTTCTTGAGGTMCCTGATCCAGCCGGATGTACCTTAGTGTACTGMTAGCCTA MG

CCATGTTCCTATCAGATGTATGACCTGGCATGTTGTMTATTCATTTCCATATGCMGT TMC

ATCATTTCCACCTAGGGATCTCTTGGAGGCTCTCAGATTTTAMGGAGATGTTCCTCA TCTTC

TTTACACGATATGACTGTCGGATGTTGCAMTGTTTACTAGCAAGTCTAGCTAGTCAA TGTCT

TCGGTTTCGTTGTTCAAAAAAAMA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

70 GGATGGCCCGAGCGGGGAACAAGAACATACAAGCCAAGCTGGTACTTCTTGGGGACATGG

GAGCTGGAAAAACAAGTCTGGTGCTGAGATTTGTCAAGGGCCAATTCCACGAGTACC AGGA

ATCCACTATCGGCGCAGCCTTCTTTACTCAGGTCTTGTCCCTGAACGAAGCGACTGT GAAGT

TTGATATATGGGATACGGCCGGACAGGAAAGATATCACAGCTTGGCTCCAATGTACT ATCGA

GGTGCTGCTGCAGCTGTCGTTGTCTATGACCTCACTAGCATGGACTCATTTCAACGA GCCAA

AAAATGGGTTCTAGAACTGCAGAGACAAGGGAATCCCAAGTTAATAATGTTCTTGGT GGCGA

ACAAGGCGGACCTGGAGCAGAAAAGGCAAGTGCTGAGTGAGGAAGGCGAGCAATATG CTA

AGGAAAATGGTTTGTCGTTTCTTGAAACTTCAGCAAAGACTGCACAGAATGTCAATG AGCTT

TTCTATGAGATAGCGAAGAGAATTGCAAAAGCTACTCCTTCACGACCGACTGGAATG AAGCT

GCAGAGACAAGAAAGTCGAAGAAGCTTATTTTGTTGCTCGGGGTGATTCCAGTGCTT GCTCT

CTTAAGGAAATTGCTGCGAATGGCTGTGGTGGATGCACCTCTTGTGGTTGTCGATGT TGAA

GATGGAATCTCATTCTGACCCTGGCTCGTGAATACTTTCATATGTACACAGTATTTC ACCGG

ACAAAATCCTTTGCTTACCATTTCAATTGTATCAAATTCTCCTTCATGTGGAAAGGG TTATGA

AAACTCGTAAGCAATAAGAAATGTTGCTCCAAAAAAAAAA

71 GTCGGAGGGGAGTAACCATGTCGACACTCAGCGAAGACGACGAAACCGAAATCCTCCTGC

GGCTTCCCGTGAAATCTCTGCTCAAGTTCAAGAGCGTGTGCAAGCCATGGAACTCAC TGAT

CTCCTCTCCCTATTTCGCCAAGACCCATCTTCAGATTTCCGCTTCTTCCCCAAGAAT CCTCCT

CGCCACCAACCCTCCTCTGTCCGTGAGCTGCGAATCACTCCATGATGATGATCGTGC CGGC

CATGAAGGTACGCCTCTAACCCAGCTTCGGCCTCCGGTTGAAGCTCCCGACGGATGT CGCC

CCCGCATCGTCGGATACTGCGATGGTTTGGTCTGCTTGGAGTACGACGATCATCGGA TTGT

TGTCCTGTGGAACCCGGCAACAGGGGAGTCTAGAAACATCCCAAACGCTAGCTGCTC GTAT

AACCGACCGACCATTTGCGGACTTGGCTATGATCCATCGACTGATGATTACAAAATA TTGCG

GCACTGTTCCGTTGCGGATGCGTATGGGTTTCCAGAATATAGCGTGTTCGATGTTTT CGCGC

TGAAGACTGGTTCTTGGAGGAGAGTTCATGACAAGCATGATGAATTTAACTATTGGC CGGAA

GCTGGGACCTATGCGAATGGTTTCCTTCATTGGCTAGTCGTGGGGAGAGATCCTTGG GAAC

ACAAGAAGATTGTTTCGTTCAGCATGAGCAAAGAGAAGTTTGAGGATGCGTTGTTGG CGCT

GCCGGAGGCCAATGAAGGTACTGGGTTCAGAGTATTGGGAGTTGCCGGTGAATGCCT TCTC

ATATATAAAAGCATGGCGGAGGTGGACACTTTTATGGCATGGATGATGAGCGACTAT GGTGT

GAGATCGTCGTCGTCTTGGATGGAGTTGTGTAGTGTTACTCTCCCGAATCAGACATT AAACA

CTTACTTCTACATGAGGCCATTGTGCTCTACCAGAGCAGGGAAGATAGCATTCAGTT CGATC

GGCACAACCCGCTTATCTATGATCCTGAGAAATGTTATGACAAAGTGGTTCGTGAAG GAGGA

TAAATTAGACTTTGTAGTGTACGTTGAGAGTTTTGTTTCACCTCATGGAGCAAAGCT GCAGAA

TCAATATGTGTCTCGGGTGAAGGAGCCTATGGAGAGAAGTGACTTCATTGGTGATCA CTCA

GTATTTAAAGAAGGGGAAACTTCATATAAGAAAGCCAATAGCCATCTTAGCAGTAAA AGGAG

AAAAGCTTCCTAGAGGGCTAGTTGTGATGTGGATGCGCAGGTCGATATATTGTGAAG TCAAA

GGGGTGACTCAGTAACTGCTTTAGGCACTTTGTTCTTCTCTTTTGTGGGTTCCTTCT GGATTA

CTTTGTGTGTCTGTGTTTGGTCGGGATGGCAGACTTGTTTCTTTGTTTACTTGTATA ACATTT

TTGTAATTCCTCTTTCCACAAATCAAAGCCCTGATGAAAACCAAAAAAAAAAAAAAA AAAAAA

AAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

72 AGAGAGAGAGAGAGAGAGAGAGAGAGATGGAGATATTCCCAGTGATTAACTTGGAGAAGT T

GAATGGCGAGGAGAGAGGAGTTACTATGGAGATGATAAGAGATGCTTGTGAAAACTG GGGC

TTCTTTGAGTTGGTGAATCATGGGATATCCCATGAGCTGATGGACACGGTGGAGAGG CTCA

CAAAGGGTCACTACAAAGAATGCATGGAGAGGAAATTCAAGGAAATGGTGGCAAGCA AAGG

GCTCGAGGCCGTTCAGTCTGAAATCGGCGACATTGATTGGGAGAGCACCTTCTTCTT GCGC

CATCTCCCCGTCTCCAACATCTCTGAAGTCCCTGATCTCAAAGAAGATTACAGGAAG GTGAT

GAGAGAATTTGCACTGGAGATAGAGAAGCTAGCAGAGCAACTTCTAGACCTGTTGTG TGAG

AACCTCGGTCTGGAGAAAGGGTACCTGAAGAAGGTGTTCTATGGATCCAAAGGGCCA ACAT

TTGGAACCAAGGTGAGCAACTACCCTCCGTGCCCGAACCCAGAGCTTTTTAAGGGCC TCCG

GGCCCACACCGACGCCGGTGGGATCATCCTTCTCTTCCAGGACGACAAGGTCGGCGG CCT

TCAACTCCTCAAGGACGGCAAATGGATCGATGTCCCTCCACTGAGGCATTCGATTGT CATCA

ACTTAGGCGACCAGCTAGAGGTCATTACAAATGGCAAGTACAAGAGCGTGGAGCACC GGGT

TATTGCGCAGTCAGATGGGAATAGAATGTCCATAGCATCGTTTTATAACCCTGGAAG CGATG

CTGTCATCTGTCCTGCACCAGCACTATTGAAGAAAGAAGCAGGAGAGGAAGGCCAAG CTTA

TCCCAAGTTTGTGTTTGAGGACTACATGAAGTTGTATGCAAGGCTTAAGTTCCAGGC GAAGG

AACCGAGATTCGAAGCCATGAAAGCCACGGAATCCACCATTGCTAGGGGTCCTATCG CAAC

TGCTTGAGTGTTGAATGACAAGTTTCTTGTTACTAAGAATAGGGTCTTGTTTCATGG TCTACT

AATGTAATGAATCTCGCTCTTTATCTAGTGCTGGAGAGTGGCTGCTTTGCTTGTGTT AAGTAA

TGTGTTTATCATGACCTTTGAACTAGTGATTTCTGAGGCTTTTTATTTGAAAAAAAA AA

73 ATCCTTCACTCCGACTCTCCACCCCCACCATCTCCTCCTCCGCCACACCACTACCAACAC CA

CCACCATCACCACCATGCAAGTCTCTCAACCTGCTCGTCCTTCCGATCCAATATACA GGCGA

GACGATCACTTGTCACAAGCATGCAAAGACTTGGTGTCCTCTCTCCCTTCTGAAGAA GGCTG

GGTCGCAACCTCTTTCTGCTTGTACCAGGGCTTCTGGTTCCCCACTTGGCTCTTCAA CGGTG

TCCTCGCTTGCCAAAACCACTTCCAAGCTCAACCCTCTGACATCCTCCTCGTCACCA ACCCG

AAATCCGGCACCACCTGGCTAAAGGCCATCCTCTTTGCTCTCTTGAACCGTGCCAAG TACTC

TGACTCCGACTCAAAACAACGCCACCCTCTTCTAACCCAAAACCCCCACGATCTTGT GCCCT

TCTTGGAGGTCAAGTTGTATCTCCAGCAAGAAAATCCCGATCTCACTACTTTCGAGT CCCCG

AGGCTCTTCGCCACCCACTTGCCCTATTCGTCACTTCCAGGGTCGGTGAGGGACTCC AGGT

GCAAGCTGGTTTACCTGTGTAGGAACCCTAAGGACATGTTCATCTCGCTGTGGCACT ACGT

CAACAAGCGGAGGGCCGAAGAGAAGGGCCAGATTCCGCTCCCAAAGTGCCTTGACAA GTT

CTGTCGAGGATTGAGCCCCTACGGGCCTTATTGGGATCATGTGATGGGTTACCACAA GGCG

AGCTTGGAGATGCCTGAGCAGGTGTTGTTCTTGATGTACGAGGAGTTGAAAGAGGAC CCGC

GTGTTCATGTGAGTAGGTTGGCTGATTTCTTGGGGTGTCCGTTCAGCGATGAAGAAC TGAG

AGACGGCACTGTAGAGGGAATAATGAGGATGTGTAGCTTCGACAATTTGAGCTCATT GGAG

GTGAATAAGAGCGGGAAGCTGTGGACTGGACAAGAGAACCAGTGGTTTTTCAGGAGA GGG

AAGGTCGGAGACTGGGTGAATTATCTGAGTGCTGAGATGGCCGACAAGATTGACCAG GTAA

TGGAAGAGAAGTTGCGTGATTCTGGGTTGAACTTTCAGTACAAATAACTCACTCGTT CAATA

ATTTCCGTGGGCTGTGTTAATTTTAAAGATGTTTGGTTTGATGGTGGAGAAAAAAAG GCACA

AAAAGTTAAAAAGGAAAAAAAAGGAAACGACTCGTTTGTTCGCACTTTATGAAAGTG TGATTC

TTATGCTATAGGATCAAAGATTTTTAGTGGCAGTGTCGATCGTGGCTTCGTATCAAT AATGAG

ACGCTTCAAGGTTGTGTTTCTGGGCACCAGCTTTGTTGTACTATTGGCTTTTGCAGA TGCTA

TTTGGCCMCACTTAGTTGGCCMTAAAMGCAGCTTTCCATCTTTTTCTTTTTGCCGTG TGA

AGCTTTGTGATGTATGGTCTTGTGTAGATCGMTTGCTAMCMCTGATATGTGTGGTTT GGA

TTAAAAAAAAM

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

74 TGGGGTTCTCTTTCTCTCTCTATAAGACGCATTGCTCCCTCTCCCTCCCCCTTTTGGCCC TC

CGTGCGCTCCAAAGCTCGCTCCTTTGAACCCCGCGCGAGCGAGACGGGGAGGTGGGC AG

CCAGCTTTTCGCCTTTCTCGAACTGGGTCGGCTCCCTTTTTCCGCCTCCCGCCTCCC AGATC

TCGCCCTCGCCCCCTCGCCGGCGGCCGGGCAAAGGCAAAGGCAAAGGCAAAGGCCGA GT

CTTTTTGATCGGCCGGTGATGCTCAGCGGCTGACGTGGGCCGCTCCTCCCCGGTTGC GCT

GCCCGCATGGATCCGACGAAGAAGCCGCGGGAGTCGTCCTCGTCGACGGCGTCGGCG GC

GGCGGCGGAGTTCCCGGACGAGGTGCTGGAGCGGGTGCTGGCGCTGCTAGCCTCGCA CA

AGGATCGGAGCGCCGCGTCCCTCGTGTCCAAGGCCTGGTACCACGCCGAGCGGTGGT CC

CGGACGCGGGTCTTCATCGGGAACTGCTACTCGGTGACGCCCGAGATCGTCGCCGGC CGG

TTCCCGAAGATCCGCAGCGTCACGCTCAAGGGGAAGCCCAGGTTCTCGGACTTCAAC CTG

GTGCCGCAGAACTGGGGGGCCGACATCCGGTCGTGGCTCACGGTCTTCGCGGAGCGG TA

CCCCTTCCTCGAGGAGCTQCGGCTCAAGAGGATGACCGTGACGGACGAGAGCTTGAA GTT

TCTGGCCCTGAAATTTCCAAACTTCAAGGCTCTCTCGCTCATGAGCTGTGATGGGTT CAGTA

CCGATGGTCTTGCGGCCATTGCGACTCGCTGCAGGAATTTGACTGAGCTGGATATAC AAGA

GAATGGCATTGATGATATTAGTGGTGACTGGTTGAGTTGCTTCCCTGAGAACTTCAC ATCTT

TGGAAGTGCTGAACTTCGCAAGTCTAAATAGCGATGTTGATTTTGATGCTCTTGAGC GGCTT

GTAAGTCGGTGCAATTCACTGAAGGTCCTTAAGGTTAATAGAACTATTTCACTAGAT CAGTTA

CAGAGGCTGCTTGTCCGTGCTCCTCGGTTAACTGAGCTCGGTACTGGCTCGTTTTTG CAAG

AGCTTAATGCTCACCAGTACTCAGAGCTTGAACGAGCTTTTGGTGGCTGCAAGACTC TACAC

ACGCTCTCTGGATTATATGAAGCTATGGCACCATATCTCCCAGTTCTATACCCGGCC TGTGC

AAATTTGACTTTCCTGAATTTAAATGATGCTGCTTTGCAAAATGAAGAACTTGCCAA GCTTGT

TGTTCACTGTCCATGTCTTCAGCGCCTCTGGGTACTTGACACTGTGGGAGACGAAGG GCTG

GGAGCTGTTGCGCGGAGTTGTCCACTCCTAGAGGAGCTTCGGGTCTTCCCGGCCAAC CCTT

TTGACGAGGAAGTTAATCATGGTGTTTCCGAATCAGGGTTTCTTGCCATTTCATATG GCTGC

CGGAGACTTCACTATGTACTCTACTTCTGCCGTCAGATGACAAATGCAGCTGTAGCC ACAAT

TGTGCAGAACTGCCCTGATTTTACACACTTCCGTCTTTGCATAATGAACCCAGGGCA ACCTG

ATTATCTGACAAATGAACCTATGGACGAGGCTTTTGGTGCAGTTGTGAAGAGGTGTA CGAAA

CTCCAGAGGCTTGCTGTTTCAGGTCTCCTAACTGACCAGACATTTGAGTATATTGGG ACATA

TGCTAAAAATCTGGAAACGCTTTCTGTAGCTTTTGCTGGAAGCAGTGACCGGGGGAT GCAG

TGTGTGCTGAGGGGTTGTCCAAAGTTGAGAAAACTTGAAATCAGGGATTGTCCATTT GGTAA

TGCAGCTCTTCTCTCGGGATTGGAGAAGTATGAGTCTATGAGGTCGTTGTGGATGTC GGCC

TGCAAAGTGACAATGAATGGGTGTGCGGTATTGGCTAGGGAGAGGCCTAGATTGAAT GTTG

AAGTAATGAAGGATGAGGAGAGCAGTGATGGTCAGGCATATAAAGTTTATGTTTACC GCACT

GTTGCTGGACCAAGGAGAGATGCCCCACCTTTTGTTCTTACTCTCTGAAGTGATTAT TTCAA

GGCATTTGTTGCTATGTGAATTTGTCTGATTGAAGTGGGGAGCACCGGTGCAGAGAG TCTG

AGGGTGTGGAATTCACAGAAAGCTCGAACATTCTGTTACCTATGTTTCTGCGGTTCA GCTAA

TTCCAGATTGTGAAGGCACACAAAATGGATAATCTGGTGGGAAAAACAACGTGTAGT GTCTG

CCTCCATTTGCTTGAAGGTGCTGGAAAGCGTATGATGCAGTCGGTGAGATGGAGTTC AAAA

GAAACACCAGAGATCTGCCAAATGTCTCGAAGCATCGGCCGACAGCTCGGGGACTTG AACC

CATGAAATTTTCCCCTTGCAAGCGCATCAATCTCTGCAACATTCTTCATCAATTGCA AGACAT

CATCAACAGCTGGGAGAAAAGATGATGATTTTCCTGATGTTTTGACTCATCTTTCCC TGGTG

ACTTCCATCCACAGCAATTGCAAGGAATCCTTTATGGATCTCTCGCTTGCAATGTAT G

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

75 ATTTTTTCATGGGGATCGTCAAGCTGATAλAACCGCACGAGGTTCTGACGAGTCCGGAT AAT

CCCCTTTTAATTMTCAAGCTTGATTAAACCGCAGCTTAATTTAATTAAGTTGATTAA TTAAAT

CGGATTCCCCGAAATGGGATGACGTGCTATAAGGACGTAGCCACTGCCGTCCGCTCG TGCA

CCCAAGGCGCAGCACCGCACGCTCTCTCTCTCTCTTCTTTCTCTCTCTATCTGCGCG TCCCG

ACTTCTGGTTCGAGCTTGTGCTTAGCTTTGCAAGAGCAGACGAAGCCGAGGTGAGAG GATC

GAGCAGCGTTGCAGCGGAGCGACCGGGCGAGCATGTCGTCGTCGGCCGTGCAGTTCG CC

GCCGCTTCTCGCGACGGCCACGAGAACAACGGCGGGGGCGGAGGGGACAGCAGCGGC G

AGCGGCTCGACCCCACCGCCGTCCTCCTCCCCGTCGATCCCGGGGCCCCCGACCTGT CCC

TCCCCCGGGAGACCTTCCTCCGGGCGGCCCTCTCTCTCAAGGACCAGGTGGTGCAGG CGA

CGTGGCGCGAGGGCGGAGCGGCCGATCCGACCGCGTACACGGGGCTGCTCGGGACGG C

GTTCCTGTGCCTGAGGTCGTACGCGGCCACCGGCGACCGGGGCGACCTGCTGCTGTC GG

CCGAGATCGTCGACGCGTGCGCTTCCGCGGCGCGTGCTTCCACGAGGCATGTGACGT TTT

TATGTGGTAAAGGAGGGGTGTTCGCGGTGGGCGCGGTGGTTGCCAATCTTCTGGGGG ACC

ATCATAAACGTGACTTCTTCCTCAACCTATTCCTCGAGGTGGCACAAGAGAGGGCTC TCCCG

GTTGGACCTGAGGAGGGCGGTTTTGGGATGTCGTACGACCTTCTCTACGGCCGAGCT GGTT

TCCTGTGGGCGGCTCTATTTCTGAACAAGAACCTGGGAGAGGAGACGGTGCCGAACA ATGT

TCTGATGCCTATTGTTGACGCCGTGCTGGCTGGGGGCAGGGCCGGTGCGTCCGATAT CGC

TACGTGCCCATTGATGTACAGATGGCATGGGACCCGGTACTTGGGCGCAGCCAACGG CCT

CGCTGGAATCTTGCAAGTGTTGCTTCACTTTCCACTCTGCGAAGAGTACCTCGAGGA TGTTA

AGGGGACTTTGAGGTATATCATGAGCAAGAGGTTTCCGCACAGTGGGAATTACCCCT CGAG

CGAAGGGAACCCGAGGGACAAACTGGTTCAGTGGTCTCACGGCGCGACGGGGATGGC CAT

CACTCTATGCAAGGCATCACAGGTTTTTCCACATGACAGAGACTTCCGTGATGCGGC CATAG

AGGCGGGGGAAGTTGTGTGGAAGAACGGGCTCGTGAAGAAAGTGGGGCTTGCTGATG GCA

TTTCAGGGAACGCGTACGCCTTTCTCTCGCTGTATCGCTTGACGGGGGAGAGAATCT ACGA

GGACAGAGCCAGAGCGTTTGCGAGCTTCCTCTACCACGATGCCAACAAGCCCGTCGG CAC

GGGGCACGGGCACGTTGCGGACTATGCCTTCTCCCTCTACCAAGGGCTCGCCGGGGC GG

CTTGCCTCTGGTTCGATCTCGTTGACGCGGAGAACTCCAGATTCCCAGGGTACGAGC TATA

AGGGAAGGAACGCGAATGCGAACACACGAGAGTTTACGTATAGCTCTTTCGTGTACA TACTA

ATGAGAGGTATGCCGTTACAAATCACGTACGCTGTTGCTCTATTGCTACAGTCAATA TATGTA

AGGATTGCAACTTGACAATCCCACGTTTGAGGCAAGAAATTGGTATCCGAAAAAAAA AA

IABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

76 AACCATCAAGTTCAGCCTTCCCCGCCGTGCAGCACTTCACCTAGATGCTTGTCGACGAAT TC

CAGTTGGCGACCTAAAGCGCTTCTCGACCAGCCAGCAGTTGCCCAGACGATTTCCGG TGAC

CTCCGCGGCATCCCCACACCGGAGACCCTTCACTGCTGCAGCTGTCCTCTGCTGATT CCGG

GCTTGGGTTGCCATTCACTGTTGTTCCTCCTGCCGATTGCTGTTCGCTACAACAGAT CACGA

CACCTGTAACATCGGCAAGCTCCCGGTTCGAλGGACCGCTCACAGACCTTCACGAA TTCAA

GATCCTCACGTATCCAAATTTCTTGAAGAGATTAATAAAGGTGAGGCCTTGAAGGGA TAAGT

CCACCATCTGGAGAGCAGCCCGTGACTTGCCTCGTGTCCATGCCTACAAGGCCTTGG TGTC

ATTGGTGTTAACTGTCCATTGAAGGAACACTCAACCCAGTAGCGAACCAGCAAGCTA CCTTG

CTGTTACGCACATGTACTGACGAACCCAGCCTTGCCGAAATTTTTAGACGATCTCAA CGACT

CGCTCCTGCACCTCAATTGTGAACCCCCCACCTTCCGACACTAGCCGCCGTTCTTGT TCGTA

TCCAAACCGAGTCGATTCTACGAAGTTCTTATTTTTGCAGGTTCGTTCACCGTGAGC CCACG

GTCGTCCTTTACTGAGGAGCACCACCGTGCCGAGCTTCAAATTTTGTTCTTGTCGAG TTCAA

ATTTTGCAATATTACTTGTGAAAATTTAGGATTAATAGGCTTCAAAGCTTCTCCTTA CAAAGAT

GCAAATCTTGCCCAGTCCTGAAGAATCCATCACCTGTAGTGGCCCGCACTATGACAG AGCG

AAAGAAGCAAAGGAATTCGACGAGACCAAAGCCGGCGTCAAAGGCCTCATCGACTCC GGC

ATGGCCAAGGTCCCTCGGCTCTTCATCCACCCTCCCCAGAACCTGCGCGACTTGTCC TCTG

ACACAGAGGGGTCCGCCACTGACCTCAAGGTCCCCATCATCGACATGATGGGCTGTC AGG

ATTCCCAGCTGCGGCGAGACGTGGTCGACGACCTCCGTAGAGCGTCGGAGACGTGGG GGT

TCTTCCAGATAATTAACCACGGGATCCCGGTCGATGTGATGGACGGCGTGTTGGAAG CTGT

CAAGCAGTTCCACGAGCAGCCTGAGGGAGTGAAGGGAGAGTGGTACTCCAGGGACGA CGC

TAGGAAATTTAGGTACTACAGCAATGGAGACTTGTTTTGGTCCAAAGCAGCAACTTG GAAGG

ACACTCTCCTGTTTGATTTCCCGTTTGGAGAGCCAGACCGAGAGGCAGTCCCTCTTC TATTC

AGAGAAACGGTTTTTGAGTACGAAAAACACGTGGAAAAATTGAAGGGATCTCTGTCT GAACT

ACTATCAGAGGCACTGGGGCTCGATTCAGGCTATCTTGGTGACATTGAATGCATGGA CTCC

AAGAGAATAGTAAGCCATTATTACCCAACTTGCCCTGAGCCAGAGCTGACTCTGGGC ACAAT

CAATCACTCAGATGCCACATATCTCACTCTTCTCCTGCAAAACCACAATGGTGGCCT CCAAG

TCCGGCACCAGAACCAGTGGGTCGATGTCTCCCCGGTGCCTGGAGCCATCCTAGTCA TCAT

TGGAGACTTCATGCAGCTTGTTAGCAACGACAAGTTCAAGAGTGTGGAGCACCGGGT CCTT

GCCAGGCGGGCTGGGCCCCGGGTCTCAGTCTTGTGCTTCCTCTTCCCAGGGGAGACG CGT

AAGTCGAAGCCGTACGGGCCGATAAAGGAGCTTCTCGACGAGAACAATCCGCCCATG TACA

GGGAGACCTCTTTCACAGAGTATTTTGGGTATTACCTCTCCAGTGGCAATGGCCTCA ATGGC

GAATCTGTGCTTCCTCATTTCAGAGTAAGCGAGCCCAAGTAGAGAGTAGAAAATGCA ACAAA

AATCTTTGAAGAAGGTGTCGGCCTTCACATGAAATCCGATGGCTGTCTTTTCATTGA ATGTA

GCGATAGGACCACACCTCGAAAAGAATAATCAGAATCTACTTTGATTTGATCGAGAC TGAAA

CAAGAAATTGCCAAAATATGATGGCATGCTCCTTCAGTCTCTGTGAAAGCATTTGAA TCTCTT

TCCCCTAAATTTATCGCGAGTTTCATCAAAAAAAAAA

IABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

77 ATAATGGATGCCGGAGATCTCGGTTCGGAGAAGTCTTCTGAGACCACGCGTGAGCTCGTC G

TCATGTCGTCGAGATTTTCAGATGGGTCCTGCTCTCGAGAAGTTTAGTGTCGGATGG ATTGA

ACTGGCTGCCCAGCTTCAATGCAATGTTAAλGAAATTAGCTTCCGGGATTTTTATC TCTTCTC

TGCTCATTACCGTTTCAGTGGCTGATAATGGATTCCCACGATGCAATTGCGATGACG AGGGA

AGTTTGTGGAGCGTGGAAAGCATTCTGGAGTGCCAGAGAGTGAGCGACTTCTTGATC GCCG

TGGCCTACTTTTCGATCCCAATTGAATTGCTGTATTTTATTAGCTGCTCGAACATCC CGTTCA

AATGGGTCCTGTTTCAATTCATTGCCTTCATTGTTCTGTGCGGATTGACCCATCTGA TCAATG

GGTGGACTTATGCCCACCATCCCTTCCAACTCATGGTCGCACTCACCGTGTTCAAGA TTTTA

ACTGCTCTCGTCTCTTGTGCCACGGCGATAACGCTCATCACCCTCATTCCTCTGCTT CTCAA

AGTGAAGGTGAGAGAGTTCATGTTGAAGAAGAAGGCTTGGGATTTGGGGCGAGAGGT AGG

GATCATAATGAAACAGAAAGAAGCTGGTTTGCATGTGCGGATGCTCACACAAGAGAT TCGCA

AATCACTTGATAGGCATACTATTTTGGACACGACCCTGGTCGAGCTGTCCAAGACAC TGGG

GTTGCAGAACTGTGCAGTTTGGATGCCTAACAATGGTAAAACCGAGATGAACTTGAC GCATG

AGAGGGGAAGGAATTACTCAGGAACCTATCACATCCCTATTCCGATAACTGATCCAG ATGTT

GTTTCAATTAAGCAGAGCGATCAGGTGCATATTTTGAGACCTGACTCAGAACTCGCA ACTGC

AAGTAGTGTAGGGCCTGGGGAGTCCGGCCCAGTAGCCGCAATTCGGATGCCAATGCT TCG

TGTCTCCAACTTCAAGGGAGGGACCCCTGAACTCCATCCAGCATGTTATGCGATACT GGTC

CTGGTCCTTCCGGGTGGAGAGCCACGATCTTGGAGCAATCAAGAACTCGAGATTATC AAGG

TGGTGGCCGATCAGGTGGCAGTGGCTCTCTCACATGCAGCAATCCTTGAAGAGTCTC AGTT

AATGAGAGAGAAACTGGAGGAGCAAAACCGGGCTCTACAGCAGGAAAAGAGGAACGC TAT

GATGGCAAGTCAGGCCCGAAGCTCATTCCAAAAGGTCATGAACGATGGGCTAAAGAG GCCT

ATGCACACGATCTCAGGGTTGCTCTCGATTATGCAGGATGAGAGTTTGAATGCGGAC CAAA

AAATTATTGGAAACGCAATGGCAAGAACCAGCGCCGTCTTGGCAAATTTGATAAATG ATGTG

GTGMCATGTCAACGAAGAATAGCGGGAGATTTCCATTGGAAGTAAGATCATTTTCTA TGCA

TGACATGATAAGAGAAGCAGCTTGCTTGGCTAAGTGCTTGTGTATCTACAAGGGGTT CAGTT

TTGAATTGGACATTGATAGGTCCTTGCCGAACAACGTAATGGGCGATGAAAGGAGGG TTTTT

CAGGTAATTCTGCATATGATCGGTAACTFGCTGAATGACAGTAATCAAGGGAAATTA GTTAC

CCTTCGAATTCTTCGTGAGAAAGCCAGTGGAAGTCAGGGAAGGTATGATCGAGGTTG GGTG

ACGTGGAGGTCCGAATCAACTGATAGAGGTGTGCGTATCAAATTTGAAGTTGGAATA AGCG

ACGACATTTCTCTGTTGGAGAGGTCAGTTTCGACAATCCAGCTTGGAGGTCGGAAAT ACAAC

AGTGATGGGGTTGAGGAGGACTTCAGCTTCAGCATCTGCAAATGGCTAGTACAGTTG ATGC

AAGGTAACATCTGGGTAGTCCCGAACACTCAGGGCTTCGCTCAGAGCATGACACTTG TCCT

ACGGTTCCCACTCCGAGAGTCCATCTCAGTGACCATTTCTGAACCGGGGCCATCTCC AGAT

TATACACTCTCCAACTCAGTCTTCACAGGCTTAAAAGTATTGCTCGTGGACTCTGAC GATGC

GMCMGGCCGTCACCCGGMGCTTCTTGAGAAGCTAGGCTGCAAGGTGTCCACTGCCTC T

TCGGGATTCGAGTGCCTCGGCGCTCTCCGCCCCTCTGMTCTTCTTTCCAGATTGTCC TTTT

GGATCTTCACATGCCCAGCTTGGACGGGTTTGAAGTGGCAMTMGATTCGCCAGTTCC AC

AGCAGTACCMTTGGCCAGTGATTGTCGCCTTGACCACTAGCGGTGACGATATTTGGG MC

GATGTTTGCAGGTCGGMTCMCGGAGTTATCAGAAMCCAGTCCTCTTGCACGGMTGGC

CMCGAGCTTCGGAGAGTCCTGTTGCAGCCMGCMGACGCTGCTATGAMTGTGGATGM

GCTTCATTCCMGATGTMTGCCTCMTGTCMTMCTTACCCTTCCTCCTTATTACCTACC A

AGATTTTCMCATATAAMGTTGTCCTACACACAAMGMGGCTCAGTCACCATTAGAMTG T

MCATACTAGTCCTTTTTCATGCCCTTGCTTTTTATGCATTTTGTAGTGATCAGAGAT CCTTTC

TAGATTGCCATTTTGGCAAMCATGTCAGCTCTTCGAGAAMCTAMTTATTGCTTGCTA GTT

TTTAMCGATACATGTATGCMCTCACATTTCAGTGAMTAGATATGMCTCTTGGCCCMM

MMM

IABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

78 CTCGCCCTCTCCCTTTCTCTCTCTACCCTTCACTCTCTCTCTCTCTCTCTCTCTAGAGAA AGA AGGAATTGAACGATAGCAATGGCGGGTTACAGAGCCGAAGACGACTACGATTACCTGTAC A AGGTGGTGCTGATCGGGGACTCCGGGGTGGGCAAGTCCAACCTCCTCTCCCGCTTCACCA AGAACGAGTTCAACCTCGAGTCCAAGTCCACCATTGGCGTCGAGTTCGCCACCCGCACTC T

CACTGTCGACGGCAAGGTCGTCAAGGCTCAGATTTGGGACACCGCCGGTCAAGAAAG GTA

CCGTGCCATCACTAGTGCTTACTATCGTGGAGCTGTAGGTGCACTCCTTGTGTATGA TGTCA

CTCGCCATGCAACATTTGAAAATGTGGATAGATGGCTGAAAGAATTAAGGAACCACA CAGAT

CCAAGCATTGTGGTGATGCTTGTTGCGAACAAGTCTGACCTTCGTCATCTTATAGCA GTCTC

AACAGAAGATGGGAAATCCTATGCTGAGAGGGAATCGCTGTACTTCATGGAAACCTC TGCA '

CTAGAGGCAACAAATGTAGAAAATGCCTTTGCAGAAGTGCTAACGCAGATCTACCGT ACCAC

TAGTAAGAAGACAGTGGAAGGAGATGATGGATCTGCTGCTGCGTTCCCTTCTCAAGG AGAA

AAGATAAATATCAAGGATGATGTCTCTGCTTTGAAGAAAGTTGGCTGTTGCTCAACT TAAGGT

TGGAGGTGATTGTTGCTTGCATAGATTAATACTTTGATTTCAGTTGTATAACATTTT TCATGCC

CAAAAGCTGAAGAAAAGTTAGCTAGAAGAAACTTATGAGACACTAAATTTGTGCAGC AAAAG

CTTAGTACATCATGCCTTTGGCATGGCAGTAGGATAGCTGCATAAGTTAGTTATTTC TCTGTT

CTGATTCATGCAAAGCCATTATTTAGGCAGTTTCATCTTTCTGAGAATTAACAAGAT GTTGCT

TTAAAAAAAAAA

79 GCAACCAACCTCCTCCTCCACCTACGCCACCACTACCACCACCATCACCACGCAACGCAC C

GCGGCCGCGGCCGCCACCATGCAACCCTCTCAACCTCCTCCTCTCAATGAAAATTAC TTGC

GAGACGACGTCAAGTCGCAAGAATGCGAAGACTTGCACTCCTCTCTCCCTTCGGAAG AAGA

CTGGGTCCCCACCTCTCTCCCTTCGGAAGAGGACTGTGTCCCCTCCACTCTCCGCTT GTAC

CAGGGCTTCTGGTTCCCCTCTTGGGTCTTGAACAGCGTCGTCGCTTGCCAAAATCAC TTCCA

AGCTCACCCCTCCGACATCCTCCTCGTCACCAGCCCGAAATGTGGCACCACCTGGCT AAAG

GCCATCCTCTTCGCTCTCTTGAACCGTGCCAAGTACTCTGACTCCAACTCACAAAAA CGCCA

CCCTCTCCTAACCCAAAACCCCCACGACCTCG.TGCCCTTCTTGGAGTTCAGGCTCT ATCTCC

AGAATAAAAATCCTGATCTCACTGCTTTTGCATCCCCGAGGCTCTTGGCCACCCACT TGCCT

TATTCCTCTCTTCCACGGTCGGTGAGGGACTCCAATTGCAAGCTGGTTTACTTATGT AGGAA

CCCTAAAGACACTTTCATCTCGATGTGGCACTACTTCAACAAGTTGAGGCCCGAAGA GAAG

GGCCAGCTTCCACTCCCGGAGGGCCτCGACAAGTTCTGCCGAGGTGTGMCTGGTGT GGG

CCTTATTGGGACCATGTGCTGGGTTACCACAAGGCGAGCTCGGAGATGCCCGAGAAG GTTT

TGTTTGTGAAGTATGAGGAGATGAAAGCGGACCCGAGCGTTCAAGTGAGGAGGTTGG CCG

ATTTCATGGGGCGTCCATTCAGCGAAGAAGAACTGAGAAACGGGACCGTGGAGGGAA TATT

GAGGATGTGTAGCTTTGACAATTTGAGTGCACTGGAGGTGAATAGGAGCGGCAAGTT GCCA

TCTGGACTAGAGAAGAAGTGGTTCTTCAGGAAAGGCGAGGTTGGAGATTGGGTGAAT TACA

TGAGCGCTGAAATGGGAGAGCAAATTGACGGTGTCATGGAAGAAAAGTTGCATGGTT CTGG

TTTGAAGTTTTAGGACATATGACCCACTCGAAGATGTTTGGTTTGATGGTGGAAAAG AAAAAT

GTGTGTAAAAAGAAGAAAAAAGAAGCAAAAACGATTCGACTCTCCGCACTTTAGGGG GTCAA

TGTCTGGATGAAAGATCTTCAGTGGCATTGTCAGTCCTGGTTTCGTCTCCATAGTGA GATGC

TTTAAGGTTGTGATTCTAGTCTTCATCTGTGTTTTGTACTATTGGCGTTTGGCAGAA GTTATTT

GGCCAGTACGTAGCTGGCTAAACAAGAGCTGCCTAGCTGCTCCCTGGGAGCTTGTGG ATGT

ATCTTCTGTTATTTATTTCAATTCCATTTTTCTTTTTCAAAAAAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

80 GTTCGCCGAGCATCATCGAAGCGACCGTCCGTCCTCCCCTCCCCTCCCGATCGCGCATGA

GGTTTCCTCCTAGATCCGGCTGATCGACTAGGGGGGCGATGGCGATTCTGTACGCGG TGG

TCGCCCGGGGCACCGTCGTCCTGGCGGAGTTCAGCGCCGTCACCGGCAACACCGGCG CG

GTGGCGCGCCGGATCCTCGAGAAGCTCCCCTCGGAGGCGGACTCCAGGCTCTGCTTC TCG

CAGGACCGCTACATCTTCCACATCCTGAGATCCGACGGCCTCAGCTTCCTGTGCATG GCCA

ACGACACCTTCGGAAGGAGGATTCCTTTTTCATACTTGGAAGATATTCAGATGAGAT TCATG

AAAAATTATGGCAAAGTTGCACACTTTGCACCTGCATATGCCATGAATGATGAGTTT TCAAG

GGTTCTGCATCAGCAAATGGAATTCTTCTCTAGTAACCCCAGTGCAGACACTCTGAA TCGGG

TCCGAGGCGAAGTTAGCGAGATGCGAACTATAATGGTGGATAACATCGAGAAGATAC TGGA

CAGAGGTGATCGAATTGAGCTACTTGTTGACAAGACTGCTACAATGCAAGATGGTGC CTTTC

ACTTCAAGAAACAGTCCAAGCGCCTTCGTCGAGCTTTGTGGATGAAAAATGCAAAGC TTTTG

GCACTGTTAACATGCTTGATTCTTGTGCTGCTTTACATTATTATTGCTGCTTGTTGT GGAGGC

ATCACTTTACCCAACTGCAGATCTTAACCTCTATAGTTGCTGGTGTTGATCTCCGGT AAGTAT

ATATGCCATGGGTGATATTTGGGTCACATTCAGGGTCCTATTTGTAACTTGAGAAGC GCTOA

AATGGAATTATGATGCGCCACTGTCTGCTAAATATCACCCTGTTGGGAGGTGCTATT CTGGT

TTTTGGGGAGTCTGATGGGGTCCATCGCTTCCATTTTCTTGATGAGTTTGTTGTGTA TTTTCA

CGGGGCATCTCTACACTGATGTAAATAATGTACTTATTTATAGCTGACAGTCGAGCT TTTGCC

AAAAAAAAAA

IABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

81 GGCAAAGTTTAGGAGAAGAATATGACAGGAACCATGATCGGAGTCACCAACGCCAATGAA C

AACAAGCCCTCGACAGAGCCCAAGAGGTCCGACAATTTGAAGACTCCAACCTTGGAG TCAA

AGGCCTCCTTGACTCGGGCCTCTCCACCCTCCCTCCCATGTTCATCCACCCGCCCGA CCTT

CTATCCAGCCTCAAGCCTGTGGTTGGGCTCAAGACCGATTCAATCCCCATCATTGAT CTCTC

CGGCTCCAACTCCGACCGACGACCCTCAGTCATCGAGGAAGTTGCACGTGCTGCTCG TGA

GTTTGGCTTCTTCCAGATAGTCAATCATGGCGTGCCCACGGAGGTCCTGGGTCAAAC GATC

GCGGCAGTGAAAGCGTTCCATGAGCAGCCAGCGGAGGTGAAGGCTAGGATCTATCGA AGG

GAATCTGAGACCGGGGTCGCCTTCTTCGCCTCCAGCGTGGACTTGCTTCACTCCAλ CGTGG

CTTGCTGGAGGTAATGTGAATGTCAATTTCTATGTTGGGTCGACAAGACAGGAACAT TAGTG

ACTCGAMTTMGAAMTTACCAAAAMGGTCTTAAATATGTTGCATGGGAGGCTAATTCA AT

TTTAMCATTTTTGACAGTTTGCMTATAGTCATTCMGCTMTTTTGGCMGMATTATTAM

GTGGACATCGTTTGTTTTATGTGACACACCTGACACTMTATTCGTMTTTTTGTATTT TTTTA

ACTTCTTTTTTTTTMTTTTTTTTTTACGTCGGCCATGCCATGTAMATTGCTTACATC CATGG

CMCGMGTTCTATCAAMTTTTATATTATCAMTGGTTAAMGATTTCAMTTMATTMTCM

ATTGAMTAGCAAAAMGCCACCAMMTTCCMATTTTACTCATTGTGACAMTATACCTCA

AACTTTTTTTGTGAGATAAMTACCCCMCTTTACCMTTGTGACACATTTMCCCAMCTT TT

TTGACACAAMGTCCCMATTTATACATGCATGACACATTTACCCCAMCTATAAGGTAT TTT

CGTTTTTTACTTTTTAMTTTTTTTTCTCTTTATTTTTCTGCTTTCTTCTCCTTTCTT CCCTCCGC

TGGCATGGTGGAGAGMGCCGGACTCAGGCGAGGATCCTTAGGTCGGGCGAGGATATC CC

TCACTAGATTCGGCMGGGCMCCCTCGCCTCACCCAAGCGAGGGCTGCCCGAGCTMTG

CCAMGAGGCACTCACCGGATTTGGCCCMGCGAGGACCACCCTCACCCGCCCMGTGAG

GGTGACCCTTGCCCGATGCCAGTGAGAGCGGTCCTCGCCTGAGTCCAGCTTCCCTCC ACTA

GCCACGGCGMGGGMGAMGMGAAGAMGAGGAMMMATTAMMMMMAMCGA

MMTGCCCTTCMCCATGGAGTTGGGGTAMTGTGTTACAGTTGATAMGTCTGGGATTTT

TTGTGTCACAMMMTTTAGGGTAMTTTATCATATTTGGTAMGTTTGGGGTTTTTTGTG G

CATTTTCCCATTAMATATTTAGMCCGMTTGATTTTTGTACTATATATATATATATAT ATATA

TATATATGACTTTTTCAGTMTTATCATCTTGMTTGATGTGMTATTAMTTGTCCTTTT GTAT

MTCGAAATTTTCATTGTCCCAAMGMGTTTCATACACACACATATTTGCAMTTATATG MT

TTATCAGTGACMTACAATGMTGGGACGMGTACTMTGCGCACCAATTTATCAGTGACM

TACMTGACGGGGCACAGAGTATTMCGTGCACGMTTTATTTGGTCTTTTTCTTMCCAT M

ACATCTTAAACATTTACACTATATAMTTAGGACACTTGAGTTCATATMTTTTCATAC TTTTTA

AAMTCTATATMTATATTAMTTTGMCMGCGAGMGMATGTTCCTCGGTGATATACMG

MGCACAMCAATGTGCAAAMGCMATAGAMGAGTGTTTGCGTTTTTTTCTTMTTMGGT

GMGMTMGMGMATTAGTTCAGTGCACGMGTMATATTACAGGGATTCGCTCCGGATA

AGGTCGGGTCCTGTACTCCCAGACGAGGMGAMTACCGGAGGTGTGCAGAMTGAGGTG

ATGGAGTGGMTCMCAGACCCMCACCTCGGAGTCCTCCTGATGGGTCTGTTGAGCGAG G

GGTTAGGATTGAGTCCGAGCAAGCTCCAGGACATGACGTGCGTGGAGMGCGMACATG TT

GGGGCATTACTATCCTTACTGTCCCCAGCCTGATCTGACTGTTGGCCTGMGCCCCAC ACC

GACAAGGGGGTGATCACGGTGCTCCTGCMGACCAGGTTGGCGGGTTGCAGGTGMGCA C

GGCGAGGCGTGGCTGGATGTGACGCCCTCTCCAGGTGTTCTCATTGTGMCATCGGCG AC

CTTCTCCAGATCATGTCCMTGACGAGTACAMλGTGTGGAGCACCGAGTGTTGGCCM TC

CAGGCCCTGMCCACGCCTGTCGGTAGCGGTTTTCTACTATCCGCTTGMTGCGAAMCC A

GATCGGACCGATCCCAGAGCTCGTGTCACCAGAGAAACCTGCTGCTTTTCGACMTTC MG

CTTGGCGAGTACCTGMGAGATTCCAMCTGAGGTGCTGGATGGGAAMCTTTGMMATCA

CTTCMGACATGATATMGAGGCATCTAGGCTMTATAGATGGTGCMGMTMGATGCTTC

CTTATTTTTMTMGMGCMTCGCTTATTMGTTGTMGTTCGGTTTGGATTCGCTAGMTTC

CMGCCATTGTCCTAGTTCMGGACGCTGTGTGCCTATATTTMGMCGAGTCATCTCGTT T

CCTCCACAATMGTCGGTATGTCTGGTAACAGGMCATATACTACTTCCTCATCCTATT TTM

CTGCACTTCTCATCGAMTTGTCTGTCCTATMCTCTCTTAC

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

82 CCGCCTTTAATATATAAATATCGTCCCCTCCCTCTCCCTCTCCCTCTCGTGTCCAAGTAA AAG

GAAAMGAAMGAGACAGAAMCAGAAMGCGGCGGCGATGGTGGTGGCGAGTCCGAACC

CACGACGGGCCGAGAAGATCCAGGCCGTCGAGCTCCCGGCGATCGACCTCTCGCCGT CG

GGGAGATCCGCGGCGCCGCGGCTCATCGTGGAGGCCTGCGAGAGGTACGGCTTCTTC M

GGCGGTCMCCACGGCGTCCCCGCCGAGATCGTGTCGAGMTGGACGAGGCGAGCGCCG

GCTTCTTCGCGCGGCCCGCCTCCGAGMGCGGCTCGCCGGGCCCGCCGACCCGTTCGG G

TACGGGAGCMGAGCATCGGGTTCMCGGCGACGTCGGCGAGGTCGAGTACCTCCTCCT C

GAGTCCGACCCCGCCTTCGTCTCCCGCAGGTCCGCCAGCATCTCCGACGACCCCACC CGG

TTCAGCGCTGCTGTGMTGTCTACATAGMGCAGTCAAGGACCTGGCCTGTGACATATT GG

ATCTTATGGCCGAGGGCCTGGGGGTCCGGGACACGTCGGTTTTCAGCAGGCTCATCA GGG

CCGTCGACGGCGACTCGGTCTTCCGGATCMCCACTACCCCCAGTGCGCGGTCCTTCA CG

GCGAGGTCGGGTTCGGGGAGCACTCCGACCCTCAMTCCTGACCGTCCTCCGATCCMC A

ATGTGGGCGGCCTCCAGATCTCACTCGMGACGGGGTGTGGACCCCGGTGCCCCCAGA CC

CCGCAGCTTTCTGGATCMTGTGGGCGATCTTTTGCAGGCCATGACGMCGGGAGGTTC TC

GAGCGTGCGGCATAGGGCGGTGACCMCCCCTTCAGGTCCAGMCGTCGATAGCGTTCT T

CGGGGCGCCTCCGCTGGACGCGCGGATCGCTCCCCAGCGGGAGCTCGTCACTCCTCG AA

GGCCCCGTCTCTACMCCCCTTCACCTGGGCCGAGTACMGMAGCCGCCTACTCCCTCA G

GCTCGGGGACMGCGTCTCGACCTCTTCMGGCCTGCAGAGMGACGGCGGCATCGATCT

GTGAGCAGATGGAGGAGATGGGTCGTCTCTTTTCTGCCCTTTTCTCTCTCTCTTGTT GCTGG

GCCTGTCGTGMGGGMTTTTGGGTTTGCGTGTTCTGCTCCCCTTCCTCTGTTTTTAGC AGC

AMGAGMGCTCTCCTAGTGTTGGTGTACTGTTGTMTCMTGGAMGGTATGTTAGGCGAC

GATATTATGTTTTGGCTTTTATCTATCMTCGACCCATCGGTTGATTTTATCTAAAAA AAAM

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

83 QTCCAGATTGCTCTCGACATGTACAGAATACAAGCAGGGTCGGCAGCAGCGGCAGGGGTC

GAGCCTGGATACTGTGTTGAGACCGATCCCACCGGTCGGTATGCTCGGTTTGAAGAA ATTC

TGGGCAAAGGGGCGACCAAGACAGTTTACAAGGCGATCGATGAGGTCCTGGGAATGG AGG

TGGCGTGGAACCAAGTGAAGCTGAATGATTCGTTTCGGTCTCCGGACGAATATCAGC GTCT

GATCTCGGAGGTTCACCTCCTCAGCACCCTCAATCACGACTCCATAATGAAATTCCA CACTT

CATGGGTCGACGTGGATGGGACGGCCTTCAATTTCATCACCGAAATGTTCACTTCAG GCAC

CCTCAGAAATTACAGGAAGAAATACCCACGATTGCACATCCGAGCCATAAAGAATTG GGCTG

TTCAAATACTTCACGGCCTCGTGTATCTGCACAGCCACGATCCGCCAGTAATCCACA GAGAT

CTGAAGTGTGATAACCTCTTTGTTAATGGACATCTGGGACAAGTTAAAATTGGTGAT CTTGG

ACTTGCAGCGATCCTTCATGGTTCTCGAGCAGCTCATAGCATCATAGGCACTCCAGA GTTTA

TGGCACCAGAACTCTACGACGAGAATTACAATGAGCTGGTCGATGTCTACTCATTCG GCATG

TGTGTCTTGGAAATGCTTACTTGCGAGTATCCTTACATTGAATGCACCAATCCGGCT CAAATT

TACAAGAAAGTCACGTCGGGAAAGTTGCCAGAAGCATTCTACCGTATCAAAGACTCA AAAGC

TCGGAMTTTATTGGAAAATGCTTAGCAAACGTCTCATGTAGAGTATCGGCAAGGGAG TTGC

TACACGACCCATTTCTTCTAAGTGATGAAGGTGACCGCCTCCCAGGATTGAAGTTCA AAATG

CCGGAGCCATTCTTGAATGGGAGAGATGTAGATAATCTGCGTGCAAGGGATAATCCA CTCA

GGACCGACATGATGATTACGGGAAAGTTGAATCCTGAGGGTGACACCATTTTTCTGA AAGTT

CAGATTGCTGATAGAAATGGTTTGAATCCCAAGTATCTTCCTGCAATCCATTAGAAC TATTGA

GAGCACAGAATCACTGTACACAATTTCTCTGATGCATCAGTACTAAGTTTTGTAAAT TAGTTA

AGAAGAAAGCATGCAGATTGTGGATTATTATCCGGTACCATTTGCAAAAAATCGATG CCTCA

AACTAGTTATATATTGCCCTAAATAGAAGTTGAAGGGGAAAATGGCTGAACGCATAT AATTCT

CAGAACTCGTTAAATTAGAGACTATAGAAATTTCTGGCCAGACTTATCTTCACAGAT CTTCCA

GAGTGATGAAACTAATGAAGGTTGTCTTCATTTCCTTCCCATTACCCATGCAGGTTC AGCGA

GAAATGTCTATTTTCCTTTTGACGTTCTAAATGACACTCCGATTGATGTCGCAAAGG AAATGG

TCAAGGAACTGGAGATCATGGACTGGGAAGCGGAGGAGATAGCCGACATGATTGGTG GAG

AAATCTCTGCTTTAGTACCTAACTGGACGAAACAGGACATGACAGACTACAATCAGG AAAAT

GACGACGGCTTTGCTCCACCTTTTCTCTCATTCTCTTCAGGTTCGTCATCACAGGCA TCGCC

ATCGGGCTTTACGGCCTACAGGGAAAATGAAATCGCGTCTGACTACGGTTGTCTCCA GGAT

GTGCCAGATGATATGAGCTCTCCAAGCTCCATACATTCTGGCACATATTCCCACACA AGTTA

CTTCTGCCCGGAAGATCAAGAAGTGAACCCCGGTCCTTCAAACCCAGATCAACACCT TATCA

GCAGAAGCAACAGACATACGAGGTTTTGCGCCGACGACTACCAAAGGCCAAGGCAAT TCAA

GGATAGGAGTCAGACCTTGCAATGCCAGGTCCTGACAGGGTCAGATAGAGATTCTTC CTCC

GTCATTAACCGGAGGATGGCCGGCCACAGACTTTCACGGAATAGGTCTCTGGTAGAT GTTC

ATAGCCAGTTACTTCACCTCTCATTGCTGGAGGAGGTGAGCAAGCGGAGGCTGTCCA GGAC

AGTCGGAGAAGTTGAGAACATCGGGTTTCAGGCACCCTTTGAGATATCAAGAAACGC CCCC

TGGATTGGCGGATCTAGTTTCATCAGCAGCTCGAGGAATAAAAAGGGCCACAGGATT CAAA

ACAGAAGAAACTGAAATCTGCCCTCTCTCATGAGCATCTAAAGATGGTAATTTGTAT CAAAAT

GTCAGCAATTTAGGACTGTATCCACCCTGCAAAGATCAAAAGTATTAGCCTTGTAGC TTAAAT

AAGTTTCAAAAAAAAAA

I ABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

84 TGTCAGTCTCCCTGTCCCCGCCTCTCCGTCTCATCATCCTCCTCCTCGTCCCTCGTCATC GC

TTTCCTCCATCAAATCAGCGTCTCCCTCCCTCCCTCGCTQACTGTGATCCCAGACCA GCGCC

GGCTGCTCCCGGGCTCGAAATCTCCGGCGACGTCGCCCGCCCGCCGACCGACCGACC GA

CCGAGCTCGCCGGAGCCATGGACGCCGGCTACCTGTTCAAGGAGGAGACCTCCCTGT ACA

ACCGCATTGTCCTCGGCAGCCTCCTGCCGGCCTCGGCCTGGGAGCCGATGCCCCGGT TAC

TCCAGACCTGGCTCCGCAACTACATCGGCGGAACCCTAATTTACTTCCTCTCCGGCT TCCTC

TGGTGCTTCTACATTTATTACCTCAAGCGCAATGTTTACGTCCCGAAGGATGAGATT CCTAC

GAGGAAGGCAATGTTGCTGCAAATATATGTTGCAATGAAGGCAATGCCATGGTACTG TGCTC

TTCCAACACTTTCCGAATACATGGTTGAAAATGGATGGACGAAATGCTTTTCAAGAA TAAGC

GATGTTGGTTGGCTTGCTTACCTAGTGTACTTGTCAATATATCTTGTAATGGCGGAG TTTGG

GATATATTGGATGCACAGAGAGCTGCATGACATTAAACCCCTTTACAAGCATCTTCA TGCAA

CACATCACATCTACAATAAGCAGAACACACTTTCTCCTTTTGCCGGCTTGGCGTTTC ATCCTC

TAGACGGGATACTGCAGGCGGTGCCACATGTTATGGCACTATTCCTTGTGCCAACCC ATTTT

ACAACGCACATTGCTCTCCTTTTTCTCGAGGCCATATGGACAGCAAATATCCATGAC TGCAT

CCATGGTAAGCTTTGGCCTGTGATGGGCGCTGGTTATCACACCATCCACCATACCAC CTATC

GCCACAATTATGGTCACTACACCATCTGGATGGACTGGATGTTTGGAACACTCCGAG ACCC

CATAGATGATGGATCCMGAAGGAGATGTAATTTATGAAGGGTTTCGTGCCAATTGTT GTCC

AAATTCTTATTTGACTTGGGTACTTGAATTTTTATTTGCGTTGCTTCTTAATCGTAG TACTTGC

TTGTAAATGTTGGTCCCTATTGAGATTGTTCAGCATCCTGGACTAGCAAAGACTTTT AAAGTA

GAAGAGGAGATTTATACTACAAAAAAAAAA

85 AAAACAATGAAAAACCCACACTCGCTAGCAAGGGAAAGGTAAGTGCTTCACTTTCATGTG CT

TGTTTCGATTCGTACTCAAAACAACAAGCCTAGCGGTTCCACCACCATGGCACACCA GCAAC

TTTGTTCGCAGTCCGCCATAGCAGGTACTGAAGAGCATGAGCGGAAGGAGACTGATG AACT

CATTGCTTCACTTCCCCAAAGGAAAGGCGCGGTTCGTCCTTTCCAGTGCCTTTACCA AAACT

TTTGGAGCCCCATCTTCGTGCTTCCCAACGTGATCACGTTTCAACGGCACTTTGAAG CCAAA

CACAAGGATATTGTTCTGGCCTCTCAGCCCAAATCAGGGACCACCTGGCTAAAGGCC CTAG

TGTTTTCCATCGTTAACCGCTTCCGCTTCGGCATCTCCAACACGCCCTTGCTCACTT CAAAC

CCCCATGAACTCGTTCCATTCTTCGAGTTCCAGCTGTACGGAAGTAAACTGAGGCCC AACCT

TGATGGCCTGGCAGAGCCGAGGCTCTTCGCAACGCACATCCCTTATCCATCCTTGCC GGAG

TGCATCAAGCGGTCTGAATGCCAAATCATTTACATTTGCCGGAACCCGTTGGACACC GTGGT

TTCCTCTTGGCACTTCTTCCTTGAGAAGGCGCGATTAGAAGACCAGCCAGAGTGGTC ATTG

GAAGAGCATTTCGAGACCTATTGCCAAGGGACAATCTCGTTCGGGCCCTTTTGGGAT CACA

TCATGGGGTATTGGAAGATGAGCTTGGAGTGGCCATCCAAGGTGTTGTTCCTCAAGT ATGA

GGACCTGAAGGAGGATACTGTAGTACACCTGAATAGGGTGGCCGAGTTTGTGGGTCT TCCC

TTTACTGAGGAGGAAGAGGAGGCAGGTGTGATTGAAGAGATAGCCAAAATGTGTAGC TTGA

AGACCCTAAAGGACCTAGAGGTCAACAAATCCGGCAAAGTAGCCTTGACGATCGAGT TCGA

GAAGAGAAGCTTTTTTAGGAAAGGGGAGGTGGGTGATTGGGTTAACCATCTCACTCC TTCC

ATGGTGGATCGCCTCAATAGCATCATCCAAGAAAAGATGAGCCCCTTTGGGTTGGAA TTCAA

AACGTGTTGAGCGTTAAATACTTTCACTTTCTCTACTTGTGTCACTAGAAATAAGTG AMTTA

ATAATGGATCTGCAATCTTCCTTATTGATGTAGTATAGAGAACTTAAGAATCCTTGA CTTCTC

TGTCGCAAGAGAAGAAACAAGTATTTGAAGCTGGTCAGGTGTGAλGAAAAAAAAGG AAGCA

TTGGTAGCATCGGTAGACTACATCTATGCTGTAAACTATTCCTATCCTATAATAGTT GCATGT

ATTGTCTACGTGTTCAGTCAATTAGAGATCATGTATTCACAAATTTACTATTAATTC ATCAACT

TTTCAAAAAAAAAA

IABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

86 CTCTCGTACCCCCCACCACCAACCATGCCTGAATCCCGTGAAGACTCTGTCTACCTCGCC A

AGCTCGCTGAGCAGGCTGAGCGTTACGAAGAAATGGTCGAGAACATGAAGCGCGTCG CCT

CGTCCGACCAGGAGCTCACCGTCGAAGAGCGCAATCTCCTTTCCGTCGCATACAAGA ACGT

CATCGGCGCCCGCCGTGCATCGTGGAGAATAGTATCCTCCATCGAGCAGAAGGAGGA GTC

GAAGGGCAATGAGGCCCAGGTCTCCATGATCAAGGGCTACAGGGAGAAGATCGAQCA GGA

GCTTGCGAAAATCTGCGAGGACATCCTCGAGGTGCTCGACAAGCACCTGATCCCCTC TGCG

GCCTCGGGCGAGTCCMGGTCTTCTACCACAAGATGATGGGCGACTACCACCGCTACC TTG

CCGMTTCGCMCCGGCGATMGCGGAAGGACAGCGCTGACAAGTCGCTTGAGGCCTACA

AGGCCGCATCTGACGTCGCCGTCACCGAGCTCCCCCCGACACACCCCATCCGTCTTG GTC

TCGCCCTGMCTTCTCCGTGTTCTACTACGAAATCCTCAACTCGCCCGACCGTGCATG CCAC

CTCGCAMGCAAGCATTCGACGACGCCATCGCCGAGCTCGACACGTTATCAGMGAGAG CT

ACAMGACTCGACCCTGATCATGCMCTGCTCCGGGATMCCTGACGCTCTGGACCTCGG A

CATGCMGACTCTGCTGACMGCCCGCCGACACAMGGAGGAGGCTGGGGATGCACCGGC

AGAGGATTAGATATTGCACGCGCTCGTTTCTTGTTACCCCTCACTTCATGCCATGCT ACATC

CCCCCCTTCCGTACACGTCCTCCMTCCMTGTTATTTCTTATTAGCGCTAAGACCTTA CCTC

TGGATCCCTTCGTTGAAMTMTGMTCCCTTTCTGCTCTATAAAAAAMM

87 AGCGTAGTTCTTTCCCGCAGCTCTCTACTTCGCTCTTCTTCTCMCCCCTGMGCCACCATG

AGTTCCTCCTCCTCCGGCGGCGACGGCGGCGGCGGCCCGAAGCTCCCTCACGACGTC GC

CGTCGACATCCTGMGCGGTTGCCGGCGAGATCCCTCCTCCGATTTAGGTGCGTCTGC CGA

TCGTGGCGTTCCGCCATCGACGACCCTCGTTTCGTGGCCCTCCACTTGAGCCACTCC GCCC

TCCACGCCTCCAGTCGGCATCTCGCGTGTCTAGATTGCGGCGMGACGCCGTCCAGMC C

GGTGCTCTCTGTTCCCCMCGCCCCTCTCGCCCTGCCTCCTCCCCCGTTGCAAATCGA MT

CCCGTTCGTTGCTCCTCCCMCCGTTACGCCCTCGTCGGTTCGTGTMCGGTTTGATCT GC

GTCTCGGAGAGTTCCAGTGACGGCACTGAGCGGGCGCTGTATTTTTGGMTCTATTCA CCA

GGMGCATAAGGCGGTTCGGCTCCCCCGTCCGGAGCGGATGCCACCCCTCTCCGTGGG G

GGCGCTCATGTAGTTCTAGGGTTTTGTTTCGATGCGAAGTCTMTGACTATCGTGTTG TCAG

GATTATCCGATACCTAGGTATTCGCCGTCGACGCTTCCGCAACMGAAGCCTCGAGTC GAG

GTTTATTCGTTCCGTACAGATTCATGGMGACCTTGGAATGTGAGGTTCCTCTTCTCT GTGA

CAGTGCGGTCTTCTTGMTGGGMCCTGCACTGGTATTCTTTCMTGGAGAGGGGGATGG A

TACGGATCCATAGTCTTGTTCMTGTCGCAGATGAGGTGTTTGATGAMTAGCTCTGCC GGA

AGGGATCAGTCCCCATTTTGTGTTGTCCGTGGCGGTATTGMTGACTCGCTGGCTGTG TTCT

TTAGTGATGGGGAGGCTTGTTTCGTTTGGGTTATGAMGACTACGGCGTGCCAGAGTC TTG

GAGTMGCTGTATACTTTCGAGGTTACTGGACCGGTAACAGCATTTGATGGCTTTACA TGGA

ATGGCGAGCTTCTTATGGAMTAMTTGCGMGMCGAGTTTCTTGGMTCCGATCACAGCA

CMCTCTCMTTCTTCCATTATTGGCGAGATACGMTTGCTCCCCGTTGTAGAGAGCCTC GT

TCCACCTTAGATATGACTCGATTGCTGCTATATCGTCAGGTGCMGGTGCTGGAGCTC TTCT

TTATTMCAGGMTTCTGGTGATTGGCMTGCMGTACAGCTGGCTCTMCMAMTGGGGG

AGTGGCAAAGGACAGCAGAMGTGATGTTGMGTTTCTTCGGAATATAGTTTACGTGGA AGG

CMGMACMTCTGCTTCATGGTTMGCTACTTCTCCCTTCGAGCATGTTCTTAGATTGAT CG

ATTTGMGGCTATCTACTTTCAAMGGATACATGTTGTGCTTATGATTATCTATATMTG TMT

GATGGGGATAGTGAAAAGCTAAMTGTGTGAGATTTGCTTAAAAAAAAM

88 MGCAGGCTGCGAGMTTTCGMGTGCTGTCTGCTCACATCTCTCTCTCTCTCTCTCTCTTC

TGCGAGGCAGTGCGATGCCGTCCCGCCGGAGMCGCTCCTCMGGTCATCATCCTCGGG G

ACAGCGGGGTCGGGMGACCTCTTTGATGMCCMTATGTAMTAAAMGTTCAGTMCCAG

TATAMGCMCTATTGGAGCTGATTTCTTGACCAAGGMGTTCAGCTCGACGATAGGCTC TT

CACTTTACAGATTTGGGATACAGCTGGTCMGAGAGATTCCAGAGTCTTGGAGTGGCT TTCT

ATCGGGGTGCTGACTGCTGTGTTCTTGTGTATGATGTTMTGTTATGAAGTCATTTGA CAATC

TTAACAATTGGAGAGAGGAGTTCCTCATCCAGGCMGTCCATCAGATCCGGAGMTTTC CCA

TTTGTGGTCATAGGAMCAAMTCGATGTGGATGGTGGAMCAGCAGAGTGGTATCAGAG A

AAAMGCTCGAGCTTGGTGTGCTTCAMGGGGMTATACCATATTTTGAGACCTCTGCGM G

GMGGTGTCMCGTGGAGGMGCTTTTCAGTGCATAGCTMGMTGCGTTGAAMGTGGTG

MGMGMGAGATATACTTGCCAGACACCATCGACGTTGCAMCAGCAGTCAGCCMGGCC

ATCAGGATGCGAGTGTTMGMCTGCCCGATGCTTCTTCCCMTAMTGMTCCATGMGGA

TTACTCAGATATTAGCAGGTTCTGCTTGTTTTAGATGATGCTGGGTTGTACATTGCT TTTGCC

AGAGAAMTGGTTGCTGACAGATTCTTTTGTCTGGTTCCTTCCATTTATTGCCGMTCA MTG

CATTCTTGAGTGATGTCCTACTTMTTTGTCTTTCATGACGCGGCTTTTCTCATCAGT GTTGA

TTTTTGTTGGTGTAAAAAAAAAAAAAMA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

89 GTGλAGACGAAGGAGGAGAAAAGGTGAGAAGGAGACATAAGGAGAλGAAGAAAAGGTG AA

GGAGGAGGAGAAAAGGTGAAGAAGGAGAAGGAGAAGGAGAAGGAGAAAAGTTGGTCT CGA

GCTGTAAGGGGGTGAGGTTTTTGAATGGATCATCGAGATAGTGGACCTGATTGCTGG TGAA

GTCGCTGCTCCAGTTCAGGTGTGTTTCCAAACAGTGGTGTTGCTCGATAGACAGCCC TTGC

TTCGTGATGGCGCACCTGAATCAGTTCGTCGGGCGGACTGCAAACCTCTGCCTCTGC GTCC

AGCAAAATTCGAGACTACCGTATCTATCTGGGGTACCCAGCGTGGAGGATTTGAAGT ACCG

TCTCATGGGTCCCAGCGATCAGATCCGCGTGCTGGGGTCTTGTGGCCGGCTTTGCAT CATC

GACGTGGCCGACGAGATCAATGTATGGGATCCGTCCACTAGGCAAAGTATGCCATTG CCTC

ACTCAGCTGTCGAGATAAGGCGTCCATCGGCTTTGCCTATTTGCGTTTATGGATTTG GGTGT

GACGTTAGGAATGGTGCTTTCAAGTTGTTGAGGCTGATTCAGCTCGCTACTGGGCAG AGAA

GATCCGAAGTCAGTATCTATAATATGATAGATCAAAACTGGAGGCGGCTCCCGGAGA TCGC

TTACAATCTGGTTTATCCGGACAAAATGGGGGTTTTCGCGTACGGCCGTCTGCATTT AACAG

TGACTCCGGAGCGGTTGGCATGTTCCCCAGCAAAATTGCTGTTGGCTTTTGATTGTC ACACT

GAGGAATTTGAGGAGGTGGAGCTGCCTGATAATATAGATAAAAAGCGTGACATGGTT GTGG

CCGTCCTGGACGGGCGCCTTTGCCTCAGCATTGATAGAATTGACATGTTTGCCGATG TGTG

GATTCTGAGAGTATATGGATCCCMGMTCATGGGCTTGGGTGTTCTCGATACCTAMTA TG

ATGATGATAGGATTCCTCGATTTGTCTGGCCATTGGCTTGCTCCGAGGATCATCATC ACGTT

TTGGTGAGAAAGGACAATAAGGATGTCGTTTGGTATGATTTACATGCTAGGTACATC AATAG

GGTAGATATAAGGGGCATGCCAAGTTCCTTTAAAGATGCATATGTGATGTGATTCAC TTGAT

CGGAGGAATCGTCGAGAAGCAGCAAGAATTGAAAGAGGAAAATAGGGACCACAGGAA AGTA

CTCCGTGAATAGTAGGTTCTTTTCTTTTGGACTGTCTCAGATTCTTCATAGTTAGCT CTTTTCT

TTTGGACTGTCTCAGGTTCTCTTCTGGGAAGTGGTTCTGTAATATATATATTTGAGC AAAGAA

TAGATGAGATGATTGAGAACTAAAAAAAAAA

90 TCAATAGAATCAACAGATATGTAAGCCAGGTTACTTCACTCGTCCAGAATATATAAGAGT GA

GCAAGCTTTCAAGAAACAGAAAGCACATACGATTGAATACACCAATGGGAGCGTGGT TGGG

TTGTATTCTGGGGCTCATCCCACTTCTAGGCTGCTGCTTGTGGTGGTGGAATGAGAT TCGGT

ACGTGTGGCCAGTAAAGCGAAGATGTTCGGGCACCAATGCGAAGTTGCCGCCGGGAC ACA

TGGGATTTCCCTTCTTTGGAGAACTTTTCACCTTCCTCTGGTACTACAAGATTCTCC GCCGC

CCGGACGAGTTCATAAACTCTAAMGAAAGAAGTATGGTGATGGAGTAGGGATGTACA GGA

CTCACCTCTTCGGATCGCCTTCCATCATAGCATGCGTTCCATCAGTGAATAMTTTGT CTTCC

GAGCTGAGGACACATTTATCGCTCMTGGCCGAATGTCGATATTATGGGCACGMTTCT CTA

GGGGCGGTTCACGGAMGGCACATGACAGGCTCAGGAGCTTTGTCTTGMTGCCGTTMC C

GACCTGATGCTCTTCGTCGTATAGCTGCTTTGGTACAGCCGCGTTTGGTTTCTGCCC TCGAG

TTGTGGGCCCAMAAGGCAGMTTGTTGCTTTTCATGAMCTMGMGGTGACCTTTGAGM

CATCGGGAAGCTGTTTGTGAGCTTTGAGCCGGGGCCACMTTGGAAAAGATCGATGGG TTA

TTTCATGACATGCTCAMGGMTGAGAGCTCAGCGGCTCMTTTTCCTGGMCTGCATATC G

CTGCGCTCTGCAGGCCCGGMGMGGTTGAGGCTATATTCAGAGTAGAGCTAGAGGAMG

GMMGCCGMGTGMGMACTGTGACCGATCTTATGGATGAGTTACGACAMTCAAAGATG

AGGAAGGCAGAAAACTATCTGACCMGMGTGCTAGATMCATCGTCAGCTTTGTGTTCG CC

GGTTATGAGTCCACTTCACTTGCATCGATGTGGGCMTTTACTATCTTGCCMGTCTCC CM

TGTTCTMAGAMCTCCGGGMGAGMCACGTCTGTTAGCCAMACAAGMGGGGGAGTTC

ATCACGAGTGMGACATCTCGMCATGAMTATACTAAAAAGGTGGTGGAGGAGACACTM G

MTGGCCMTATTTCACATTTTCTTTTCAGATTAGTCACAMGGACATCGAGTACAMGGT TA

TAGMTACCAMGGGATGGAMGTGATTCTGTGGCTCCGGTACCTCCACACGMCCCGGM

MCTTTGATGACCCAATGTGCTTTMTCCAGAGAGGTGGAACGATTCTGTGAMCCGGAG G

CATACCMGTGTTTGGTGGGGGATCGAGMTCTGTCCAGGAMCATGCTTGCGAGMTTCA

GCTGGCTATTTTACTGCATCACTTATCAGTAGMTACMGTGGGAATTGATCMCTCGGA TG

CAGGCTTTGTCTATCTTCCCCACCCCGCACCAGTTGATGMGTTGAAGTCAGTTTCAG CMG

TTATGAGGAATGATTTGTTGGMTTTTGTTTGTTMAACAMATGAGTGCCTTTTAATTT GTCC

CACATAGMMTGTGGGAGCAGGAGGGTTAGTTTATTMTGTAGGATTTCCCTTTTATAG TTA

AAAGAGTGATTAGGTGGGGTTAGACCTCACCATGCCAAAAAMMAA

IABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

91 ACAACGCTCAAGAAGAAAATTTCGAAACGATCTCTCGCCCTCCGTTCCGCTATAAATAGC AC

CCGAGCACCAATACTCTTTCCATCATCTTCAAAACAACTGTCTCTGTCTCTCTCTCT GTCCCT

CTCTCTCTCTCTCTCTCGATTCTCTCCCTAGTCCATTAGTTCTCGTTGCCGCTTCGT AAACAA

GGAAGCACGGCGCACGGCCGTCCGATGGTTGTCCCGTCCAAACTAGCAATTGAACAG TTCT

CCTACGTTATGAACAGCAACGCATTATCATCCCACCAAATCCCTGTCGTGGACCTCT CGAAG

CCCGACTCCAAGAGCCTCATCATCAAGGCCTGCGAAGAGTGCGGCTTCTTTAAGGTC GTGA

ACCACGGCGTCCCGTTGGATTTTATCTCCAGGCTGGAGGAGGAAGCCGTCAAGTTCT TCTC

TCTGCCTCTCCCCGAGAAGGAGAGGGCAGGCCCTCCTGACCCGTTCGGCTATGGCAA CAA

GATGATTGGCCGGAACGGAGATGTGGGTTGGATCGAATACCTCCTCCTGACGACCGA TCCC

AACTTCAACTACCGCAAGCTCCCATCGGCTTTTAACGAAAACCCAGAAAGATTTCGC TCTGC

TTTGAGTGATTACACATCGGCGGTGAGGTACATGGCGTGTGAGATTCTCGAGTTGAT GGCC

GACGGATTAAGGATTCAACAGAGGAATATATTTAGCAAACTTTTGATGGATGAACAG AGCGA

CTCTGTTTTCAGGCTCAACCACTACCCTCCATGCCCGGAGCTTCAATCCTATGTCGA TAGGA

ACATGATTGGATTCGGTGAACACACTGACCCACAAATCATATCTGTTCTCAGATCGA ACAAC

ACGTCTGGGCTCCAAATATCCATGAAAGATGGGACTTGGGTTTCTGTTCCACCGGAC CAGA

ACTCATTCTTCATCAATGTTGGTGACTCCTTAGAGGTGATGACTAACGGGCGATTCA GAAGC

GTGAGGCACAGAGTCCTGGCGAACACCTCGAAGTCCAGGGTCTCGATGATATACTTC GGAG

GACCACCTTTGAGTGAGAAGATAGCGCCATTGCCGTGCCTCATGAAGGGCAAAGAGA GCCT

GTACAAGGAGTTTACATGGTTCGAATACAAGAAGTCCGCCTACAACACGAGGTTGGC TGATA

ACAGGCTAGAGCATTTTCAGAGAGTAGCCGCTTCTTGATGTCGCTCAGAGCGCCAGA TGTC

AGCAGCAAGAATGGGTTCTTAGGACAGCAACTTTCATCTTCATTTTGTTCCTTCCTT GTCTCT

CTGTATTTTCCATCGGTACTTTCTTGTTCAAACGATGTAAATTACTCTCTTCTTGTC AAATATC

ACAGAGCGTCCATGGTCTGCCACTATCTCTATTTGACAATTTGTAATATGTAATTTT CAATGA

AGTCACAGTCACAAGTCACCTTTCAGACAAAAAAAAAA

92 GACATTTACAGCTCTGAGAAGGAGGGTAGGGAGTGAGTGTGGTGGGCTTTTTTTTAGCTT CT

TGGGAGCAGCAACAATGGCTGTTTACATCTTCTTGGCTCTTGGGGTGGTGTTGGTGC TCTG

TGTATGCACTGCCTTGCTGAGATGGAACGAGGTAAGGTACATGAAGAAAGGTCTGCC TCCG

GGCACAATGGGTTGGCCAGTCTTTGGTGAGACCACCGAGTTCCTCAAGCAAGGCCCT AACT

TCATGAAAAACCAGAGTGCCAGGTATGGGAGCTTCTTCAAGTCCCACATCCTGGGGT GCCC

CACGATAGTGTCCATGGACCCAGAGGTGAACCGGTACATCCTGATGAACGAGGCCAA GGG

GCTCGTCCCGGGTTACCCGCAGTCCATGCTCGATATTCTGGGCAAGCGCAACATAGC GGC

GGTTCACGGCGCGTCCCACAAGCACATGAGGGGTGCTCTGCTCTCCCTGGTCAGCCC CAC

CATGATCAGGGACCAGCTCTTGCCTAAGATCGATCGGTTCATGCGATCCCACCTCGC CCGC

TGGGACGATGGCTCCATTATTGACCTCCAAGACAAGACCAAACAGATGGCACTCCTC TCGT

CGCTGATGCAAATCGGAATCGACTCCAGCTCCATTTCCCAAGAATTCATACCCGAGT TCTTC

AAGTTAGTCCTGGGCACTCTCTCCCTGCCTATAGACCTCCCGGGCACAAACTACCGT CGAG

GTTTCCAGGCTAGGAAAAATATACTAGGCATGTTGAGGAAACTGATAGAAGAGAGGA GGGC

CTCCCAGGAAGCCCACAATGACATGCTTGGTTGCCTCATGAGGAGTGATGATAACAA ATACA

AGTTGAATGATGAAGAGATCATTGACCAGATAATCACCATCATGTATTCCGGGTACG AGACC

GTTTCGACCACGTCCATGATGGCTGTCAAGTATCTCCACGACAACCCGAGCGTTCTT CACG

AATTAAGGAAAGAACACTTGGGGATTAGAGCGAAGAAAAGGCCGGAGGATCCTATCG AGTG

GGACGACCTCAAAGCGATGCGGTTCACTCGTGCGGTCATATTTGAGACCTCCAGATT GGCC

ACAGTTGTCAATGGGGTCTTGAGAAAAACCACTAAAGACATGGAGCTCAACGGGTTC TTAAT

CCCAAAGGGATGGAGGATATACGTTTACACGAGAGAAATAAATTACAATCTGCGATT ATATC

CCGATCCACTAGCTTTCAATCCATGGAGATGGCTGGACAAAAGCGTGGAGTGTCAAA ACTA

CAACCTAATTTTCGGTGGGGGCACAAGGCAATGCCCTGGAAAGGAACTTGGGATTGC CGAA

ATCTCCACATTTCTTCACTACTTTGTGACCAGATACAGATGGGAAGAGATTGGGGGA GACAA

GCTAATGAAATTTCCAAGAGTAGAAGCACCAAATGGGCTGCACATAAGGGTTTCCCC TCAAT

GCTGACTTCACTCCAATATTCTTATGTACAGAAGAAACCAAAAGAGGAAAAAACAAG AAGCA

CGACAAGTACAGATGTATATTAATGATTTTTGATAGATTTAAGTAGGAAAGTGCACC AAAAAA

AAAA

W

IABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

93 GGGACACGATATCCTCCCATTTAGTCAGCATGATGTGTCAAGATTAAAACCCACAGTGAC GG

GGCTCACAAGTATCTTGGCAAATTTGATGGATCCCATTTTTCGTTGGTGCTTCGTGT ATGTTT

TCTTTGTGAGTGGTAGCTGCAGGAGCTGTGAGTTTCGATCTCAGTTCGATTAATTTA GCCAA

AGAAAATGAGTGCCGAGAAAGAGAGGGAGAGCCATGTTTTCATGGCCAAGTTAGCCG AGCA

GGCCGAGCGTTACGATGAGATGGTGCAGTCAATGAAGGATGTTGCCAAATTGGATCT AGAG

CTGTCTGTAGAGGAAAGAAACTTGCTTTCTGTTGGATATAAGAATGTTATTGGTGCC AGGAG

AGCATCATGGCGGATTATGTCCTCCATTGAGCAGAAAGAAGAAGCAAAGGGAAATGA GCAG

AACGCGAAAAGGATCAGGGATTACCGTCAAAAGGTGGAGGATGAACTCTGTAGAATC TGCA

ATGACATTCTGTCAATTATTGATGATCATCTCCTTCCTTCTTCTACCTCAGGAGAGT CCACAG

TCTTTTACTATAAGATGAAAGGCGATTACTACCGATATCTTGCTGAATTTAAATCTG GAAATG

AAAGGAAGGAGATTGCTGATCAATCTTTGAAGGCTTACGAGGCTGCTTCAAATACTG CAGCT

ACAGATCTGCCTCCCACACATCCAATCAGGCTTGGCTTAGCACTAAACTTTTCAGTT TTCTAT

TATGAAATTCAGAACTCTCCTGAAAGAGCATGTCACTTGGCAAAACAAGCATTTGAT GAAGC

CATTGCAGAGCTGGATACTCTCAGTGAAGAATCATACAAGGACAGCACATTAATAAT GCAAT

TGCTGAGAGACAATCTTACATTATGGAGTTCTGATTTGGAAGATCTTGGAGGGGATG ATCAG

CCTAAAGGAGAAGAGGCGAAGGTGGAAGATGGGGAACCCTAATTTTGTTGCAATAGC GTTT

CTTCGGCAGTTGGATTGCTTGGAGGATTTTTGATATTCTTCCTGGCGTACTTCCTCA GTCTTT

TTTGTTTTGAGTGGATGTTTATATCACTTTGATGCAATACAGTTTCACTTGCATTGT GAGTTTT

TTTTTTCTAGATTGACATCCTTCGTTGGTTCTCAAAGTA

94 GAGAGCAGGTTGAGGAGGGCGTAAGTTAAATCAGCCTAGATCTCTTCGACTCCATCTTCA TT

CAACATAAGCTCGAACTCATCATGTCGGCCCGCAGAAGAACTCTTTTAAAGGTTATC ATCCT

TGGCGATAGCGGGGTTGGTAAAACCTCGCTGATGAATCAATATGTAAACAAGAAATT CAGCA

ACCAGTATAAAGCAACCATTGGAGCTGACTTCTTGACTAAAGAAGTTCAGTTCGAGG ATAGA

TTGTTCACGTTACAGGAAAGATTTCAGAGCCTTGGTGTTGCCTTCTACCGTGGTGCC GATTG

CTGCGTTCTTGTTTACGATGTTAATGTGCTAAAATCATTTGATAACCTAAATAATTG GCGCGA

TGAATTTCTAATTCAGGCAAGCCCTTCTGATCCGGAGAATTTTCCATTTGTTGTGCT TGGAAA

TAAAATTGACGTGGATGGTGGGAACAGCAGAGTGGTCTCTGAGAAAAAGGCCAGGGC ATG

GTGTGCTTCTAAAGGCAACATTCCCTACTTTGAAACTTCTGCAAAAGAAGGCTTTAA TGTTGA

AGCAGCTTTCCAATGTATAGCCAAGAATGCATTGAAGAATGAGCCCGAAGAGGAAAT ATATC

TCCCGGACACAATTGATGTCAATGCTGGGAGACCACAAAGAACATCAGGATGTGATT GTTAG

TCACCAGGGGATTGTACAAGACTTTGATGCTACAAATAATAGTTTACTTGCATCGTA AGATAT

CGAACTTGAATCAGGCCATTGGGGTGTTAATCAAACGTTTACTTGTGTAACCAGTGT AGAGA

TAGAATTGTACTCTAGTAATGCTCATTAAAAGTTAGATTGTTGTTTTGCAATTTCGC AAAAAAA

AAA

95 CATTCCCCAATCCCCTTTTTACTTTTTGCGGAACAGGGACCGGGGGCAGCGATCTATTGA CC

AGAGACCAGAGAGCAGGTTGAGGAGGGCGTAAGTTAAATCAGCCTAGATCTCTTCGA CTCC

ATCTTCATTCAACATAAGCTCGAACTCATCATGTCGGCCCGCAGAAGAACTCTTTTA AAGGTT

ATCATCCTTGGCGATAGCGGGGTTGGTAAAACCTCGCTGATGAATCAATATGTAAAC AAGAA

ATTCAGCAACCAGTATAAAGCAACCATTGGAGCTGACTTCTTGACTAAAGAAGTTCA GTTCG

AGGATAGATTGTTCACGTTACAGATATGGGATACCGCTGGCCAGGAAAGATTTCAGA GCCTT

GGTGTTGCCTTCTACCGTGGTGCCGATTGCTGCGTTCTTGTTTACGATGTTAATGTG CTAAA

ATCATTTGATAACCTAAATAATTGGCGCGATGAATTTCTAATTCAGGCAAGCCCTTC TGATCC

GGAGAATTTTCCATTTGTTGTGCTTGGAAATAAAATTGACGTGGATGGTGGGAACAG CAGAG

TGGTCTCTGAGAAAAAGGCCAGGGCATGGTGTGCTTCTAAAGGCAACATTCCCTACT TTGAA

ACTTCTGCAAAAGAAGGCTTTAATGTTGAAGCAGCTTTCCAATGTATAGCCAAGAAT GCATT

GAAGAATGAGCCCGAAGAGGAAATATATCTCCCGGACACAATTGATGTCAATGCTGG GAGA

CCACAAAGAACATCAGGATGTGATTGTTAGTCACCAGGGGATTGTACAAGACTTTGA TGCTA

CAAATAATAGTTTACTTGCATCGTAAGATATCGAACTTGAATCAGGCCATTGGGGTG TTAATC

AAACGTTTACTTGTGTAACCAGTGTAGAGATAGAATTGTACTCTAGTAATGCTCATT AAAAGT

TAGATTGTTGTTTTGCAATTTCGCAAAAAAAAAAAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

96 AAGCGGTGGTATCAGCGCAGAGTACGCGGGGACTCCTTATATTGTCTCTCTGTGTTGAAT G

CTGTGACCATGAAGCGGGCGAGCTATGGATGCATATCGGACGAAGCCCTGGAGTGCG TTAT

GGGCCACCTGGAGGATCCGAGAGACCGTGGCTCGGTCTCTCTGGTCTGCAAGAAATG GTA

CGACGTGGATGCCTTCACGAGGAAGCACGTGACCGTGGCCTTCTGCTACTCAATACA CGCC

AGCGACCTTACCCGCAGGTTCACCAGGCTGGAGTCCCTTACGGTCAAGGGGAAACCC AGA

GCGGCCATGTATAATCTGCTCCCTCACGATTGGGGGGGTTATGCCAAGCCCTGGATA GACC

AGATCTCCTTCACCTGTCTCTGCCTCAAGGCGCTCCATCTGCGCAGAATGATTGTTA CCGAT

GATGATCTCACCACTCTCGTCAGGGGCCGCGGTCACATGTTGCAGGAGCTCAAACTC GAGA

AGTGCTCTGGGTTCTCTACAAGGGGGCTTGAGGAAGTGGCTCACGGTTGCAGGTCTC TTAA

GATCTTAATGCTGGACGAGAGTCAAATTGAAGAGGAAAGCGGGGACTGGCTACATGA GCTT

GCTCTTAACAATTCTTCTTTGGAAGTGTTGGACTTCTACATGACAACATTAGAAATG ATCAAT

ACCAGTGATCTTGAGCTAATAGTAACAAACTGCCCCTCATTAACATCATTAAAGGTT GGAGA

ATGTGATATAGTTGAGATGAGAGGCGTTCTGAGTAAGGCTACTGCATTGGAGGAGTT TGGT

GGTGGGACATTTAACAACAGTGAAGAGCATGCGACGGAGACCAGTATGATTACATTT CCTC

CAAAGTTGACATCATTGCTAGGACTAAACTTCATGATTGAGGCTGAGATGCCTGCTA TATTC

CCAAGAGCTTCGGCCCTTAAGAGATTGGATCTGCAGTACACATTCTTGAGCACAGAA AATCA

CTGTCAGTTGGCAGGGCTCTGTCCTAATCTTGAAATTCTCGAGGTTAGAAATGTTAT CGGAG

ACAAAGGGTTAGAAGTTGTTGCTAATACTTGCAAAAAGCTGAAAAGACTTAGAGTGG AACGA

GGAGCAGACGACCCAACTTTGGAGGACGAACAAGATAAAGAAGAGCACATCGCTGAT TTAC

CGCTGGACAATGGAQTCAGGGCTTTGCTACGTGGATGTCAAAAGTTGAGTAGGTTTG CATTT

TATATCAGGCCTGGAGGGCTGACAGATACAGGTCTTGGTTATATTGGCGAGTACAGC ACTA

ATGTAAGGTGGATGCTTCTGGGTTTTGTTGGTGAAACTGACCAAGGCATTCTCGAGT TTTCC

AAGGGCTGCCCAAAGCTGGAAAGGCTAGAAATTAGAGGTTGTTGTTTTAGTGAATCT GCATT

GGCAGCTGCAGTGCTTCAGCTGAAATCGCTGAAGTACATATGGGTTCAAGGATATAA TGCAA

CTGTTACTGGTGCTAACCTTCTAGCGATGGCTCGACCTTATTGGAACATAGAATTTT CTCCT

GCTTTGCAATCGAGTGATGTGTTTGCTGAAGATATGGCAGAAGAAAAAAAACAGGAT CAGGT

AGCACAACTTTTGGCCTACTATTCTCTTGCTGGAAGGAGGACAGATCACCCAGAGTC CGTAA

TTCCTTTAGCTCCACTTTTCTGGAATTGCCATCAAGTAACTGTCTTCTAATGTGAλ TATCTATA

TAAAATATGAGTCCCAAACTTGCATGGAGGTATATAAATATAGAACATGCAAAGATG CTTCTT

TCTCTCCCGTTTCCTTCAGATTTCTTTTGTGATAGTAGTGTGACTAGCACTTACTAT GCCTAA

CAGTCTGATGGAAGAAAGGTACGTTGAGACTTATCTCTCTTCCTAATTCTCTATGGC AGTGG

ATGTAGTCATTCTACCTCATAACGTGTCTGTTTATTGATGGAAACTTCTTCCCAGTG TGATGA

ACTCTTCTGGAGAGTTCTAGGGGATGTCTTGGTAGGTTCAATGGGATGTCTTCTGAA TATCA

TAATCTTCATATTTCTATCAATGAAGACATTGCTGAAAGAAGTGGTTACCACAAAAA TCCATG

TAAGTACAAGGGGTATTGCACTGACAAAAAAAAGTTCGTCCTTGGAAAACTGAAATG TTTATT

TTTTCTTCTAAGCTGGTTACGGATATTTATGGAGTTGAGATGTACGTAATCGCGAAG GTGTA

CAGTCAAAACGGGTATGTTTCATACTTTGACTTGGTGGGCTACAAGTCAAAACTTAC AGTGG

ACATACCGTGCTTCTTTTCCTAGTATGCTGGTAACATCAGTGCTGAAGTCAACAGGC CTCTG

GTTTTCAACGACATTAAGTTGTGGGTATGCTTAAGGACATCGAAATACCAAGGGCAC TAGAG

TTCAAGTAGACGTTTATAATTTAACCGGCCATTCAACATCCTGAGTTTGTAGCATGA GAAGCC

ACTTGTCTTATTTTCAGTTCTTGGTAGGGAGTTCAGAATTAGGGGGTGATTTGAGAA CATCAT

AAATAATGTCATATTTTATATCCAGAGACTTGAACTATTTGTATGTTGTAATTCATA TTGGTTG

ACATGATTGATATGTACATATGTTACATGGTATTAGCATGAGGATGTTGATGTTTGA CCTTAA

AAAAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

97 GCCGTCGGATCCACTCCCCGGCGGCCACGATCGGTTTGCTTTCCCTTTTGTCGTCTGACA C

CTTTTCCCGACCTACAGGAAGCATAGATTTTTACTGTAAGATGCGATGAGTGAGCAA TGAGC

GATGGGCATGTCGCAAAATTAGAGATAAGATCACCAAGGAACCAACAAAATCAGAGG CCGA

GGACCTCGACCAGGGGCTCTCTGTGTATATAGCTTTGAAGTCCATATGAATATATTC ACTCC

TTATATTGTCTCTCTGTGTTGAATGCTGTGACCATGAAGCGGGCGAGCTATGGATGC ATATC

GGATGGATGCATATCGGACGAAGCCCTGGAGTGCGTTATGGGCCACCTGGAGGATCC GAG

AGACCGTGGCTCGGTCTCTCTGGTCTGCAAGAAATGGTACGACGTGGATGCCTTCAC GAGG

AAGCACGTGACCGTGGCCTTCTGCTACTCAATACACGCCAGCGACCTTACCCGCAGG TTCA

CCAGGCTGGAGTCCCTTACGGTCAAGGGGAAACCCAGAGCGGCCATGTATAATCTGC TCCC

TCACGATTGGGGGGGTTATGCCAAGCCCTGGATAGACCAGATCTCCTTCACCTGTCT CTGC

CTCAAGGCGCTCCATCTGCGCAGAATGATTGTTACCGATGATGATCTCACCACTCTC GTCAG

GGGCCGCGGTCACATGTTGCAGGAGCTCAAACTCGAGAAGTGCTCTGGGTTCTCTAC AAGG

GGGCTTGAGGAAGTGGCTCACGGTTGCAGGTCTCTTAAGATCTTAATGCTGGACGAG AGTC

AAATTGAAGAGGAAAGCGGGGACTGGCTACATGAGCTTGCTCTTAACAATTCTTCTT TGGAA

GTGTTGGACTTCTACATGACAACATTAGAAATGATCAATACCAGTGATCTTGAGCTA ATAGTA

ACAAACTGCCCCTCATTAACATCATTAAAGGTTGGAGAATGTGATATAGTTGAGATG AGAGG

CGTTCTGAGTAAGGCTACTGCATTGGAGGAGTTTGGTGGTGGGACATTTAACAACAG TGAA

GAGCATGCGACGGAGACCAGTATGATTACATTTCCTCCAAAGTTGACATCATTGCTA GGACT

AMCTTCATGATTGAGGCTGAGATGCCTGCTATATTCCCAAGAGCTTCGGCCCTTAAG AGAT

TGGATCTGCAGTACACATTCTTGAGCACAGAAMTCACTGTCAGTTGGCAGGGCTCTG TCCT

MTCTTGAMTTCTCGAGGTTAGAMTGTTATCGGAGACAMGGGTTAGMGTTGTTGCTMT

ACTTGCAAAAAGCTGAAAAGACTTAGAGTGGMCGAGGAGCAGACGACCCMCTTTGGA GG

ACGMCMGGTTGGATTTCCCACAMGGGCTTTCCTTGGTAGCTCMGGCTGCCCCCTTCT T

GAGTACATTGCCGTCTATGTTTCAGATATATGCAACTCAACCTTGGAGACCTTTGGT CMTGT

TGCMMATCTCAAGGATTTCCGGTTGGTCTTGTTAGATAMGMGAGCACATCGCTGATT T

ACCGCTGGACMTGGAGTCAGGGCTTTGCTACGTGGATGTCAAMGTTGAGTAGGTTTG CA

TTTTATATCAGGCCTGGAGGGCTGACAGATACAGGTCTTGGTTATATTGGCGAGTAC AGCAC

TMTGTMGGTGGATGCTTCTGGGTTTTGTTGGTGAMCTGACCMGGCATTCTCGAGTTT T

CCMGGGCTGCCCAMGCTGGMAGGCTAGAMTTAGAGGTTGTTGTTTTAGTGAATCTGC A

TTGGCAGCTGCAGTGCTTCAGCTGAMTCGCTGMGTACATATGGGTTCMGGATATAAT GC

MCTGTTACTGGTGCTMCCTTCTAGCGATGGCTCGACCTTATTGGAACATAGMTTTTC TCC

TGCTTTGCMTCGAGTGATGTGTTTGCTGAAGATATGGCAGMGMAAMAACAGGATCAG G

TAGCACMCTTTTGGCCTACTATTCTCTTGCTGGMGGAGGACAGATCACCCAGAGTCC GTA

ATTCCTTTAGCTCCACTTTTCTGGMTTGCCATCMGTAACTGTCTTCTAATGTGAATA TCTAT

ATAAMTATGAGTCCCAMCTTGCATGGAGGTATATAMTATAGMCATGCAMGATGCTTC T

TTCTCTCCCGTTTCCTTCAGATTTCTTTTGTGATAGTAGTGTGACTAGCACTTACTA TGCCTA

ACAGTCTGATGGMGMAGGTACGTTGAGACTTATCTCTCTTCCTAATTCTCTATGGCA GTG

GATGTAGTCATTCTACCTCATMCGTGTCTGTTTATTGATGGMACTTCTTCCCAGTGT GATG

AACTCTTCTGGAGAGTTCTAGGGGATGTCTTGGTAGGTTCAATGGGATGTCTTCTGA ATATC

ATMTCTTCATATTTCTATCMTGMGACATTGCTGAMGMGTGGTTACCACAAMATCCAT

GTMGTACAAGGGGTATTGCACTGACAAAAMMGTTCGTCCTTGGAAMCTGMATGTTTA

TTTTTTCTTCTMGCTGGTTACGGATATTTATGGAGTTGAGATGTACGTAATCGCGAA GGTGT

ACAGTCAMACGGGTATGTTTCATACTTTGACTTGGTGGGCTACMGTCMMCTTACAGT G

GACATACCGTGCTTCTTTTCCTAGTATGCTGGTMCATCAGTGCTGAAGTCAACAGGC CTCT

GGTTTTCMCGACATTMGTTGTGGGTATGCTTMGGACATTGMATACCMGGGCACTAGA

GTTCMGTAGACGTTTATMTTTMCCGGCCATTCMCATCCTGAGTTTGTAGCATGAGAA G

CCACTTGTCTTATTTTCAGTTCTTGGTAGGGAGTTCAGAATTAGGGGGTGATTTGAG MCAT

CATAMTMTGTCATATTTTATATCCAGAGACTTGMCTATTTGTATGTTGTMTTCATAT TGG

TTGACATGATTGATATGTACATATGTTACATGGTATTAGCATGAGGATGTTGATGTT TGACCT

TATTTAAGTGTTCGTAGGTTGTAATTAAAAAAAAAAAMMMA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

98 ATTATCTCATCACAAAAATCTTTAATTTGCTCTTTGAACCATTCTGCATCATGTTTACAA TAAG

TACCTGTACAACTCACGCACAATCTCTGATATACAGTTTTGTTGCGAGGGGCACCGT GGTGC

TTGCGGAGTACACGGAATTCAAAGGCAATTTTACAGGTATTGCCGCTCAGTGTCTGC AAAAG

CTTCCCGCCAGCAACAACAAGTTCACATACAATTGCGATAATCATACCTTCAACTAC CTTGTT

GAAGATGGCTTCGCATATTGTGTTGTTGCAGATGAATCCGTTGGAAGGCAAGTACCA ATGG

CATTTCTGGAGCGTGTTAAGGAGGATTTTAAGAGGAGATATGGTGGTGGAAGAGCTG ACAC

AGCTGTTGCTAACAGCTTGAACAGAGATTTTGGGTCAAAATTGAAAGAGCACATGCA GTATT

GCATTGACCACCCTGAAGAGATCAGCAAACTTGCAAAAGTCAAGGCCCAGGTTTCTG AAGT

GAAAGGTGTCATGATGGACAACATTGAAAAGGTTCTTGACCGTGGTGAGAAGATTGA ACTTC

TGGTTGATAAAACAGAAAACCTTCGTTTTCAGGCTCAAGACTTCCAAAAGAAGGGAA CCGAG

TTGCGCAGAAAGATGTGGTTTCAGAACATGAAAGTGAAATTGATTGTCCTTGGAATT GTGGT

GGCCTTGATTCTCATAATTGTCCTTTCAGTATGCCATGGATTCAATTGTTCGAAAAA ATGATC

TGGAATAGATAGAGGTCCATTTGAATTGGAACAACTTTTGATTGGCTATGGATGGCA TTCTT

GTTCTCCTTTGTATTTCTCTCTATATTATCAGTTTCGGGTGAGATAGTTCTATGATG TTTGCCA

GAGGGTATTTTGCTTGGACAATCACTGGTTGATAGTACATATTGACTAGTATGACAA CGAAAT

GTTCTGAATATTCAGTGGGGCAGAGACTCTGATTGCGTACAGCAACTTTAGTGTATT ATATC

AAGGTCATGCATTTGTTATAAAAAAAAAA

99 CCCAAATTAAAAGTCGAGCGCTTAATGAAATGATAGTCGTCAGATGACGTCCGAGGGGTT TC

AAATAATTCTTAGCCGTCCATTTCGTAGAACATCGGTACTCCATCAATTTTCCTGCT CATCTT

ACCCTCATTTTGTAATTCTCTTCCTGGCGGAGGGTTTGGAAGCTGGGGAAATCAGGC GAAAT

AAATAGGGAATTGGGACTGTTTGCTGCAAATATCGTTTTTATTCGCCGAAAATCAGC TTTGG

GTCTGTGATTTGGCCTTCTGCGTTCGATTCTGCGCGTTTTCAGCTTCATTTCCAAGG CCTTTT

CGTCAGGTTTGGCTAAAAAATGACCACCGAAAAGGAGAGGGAAAATCATGTATACAT GGCC

AAGCTCGCCGAACAGGCCGAACGATACGACGAAATGGTGGATTCAATGAAGAAAGTG GCCA

AATTAGACGTTGAACTGACAGTCGAAGAAAGAAATCTGCTTTCTGTTGGCTATAAGA ATGTTA

TTGGTGCTAGGAGGGCTTCCTGGCGGATTATGTCGTCCATTGAACAAAAAGAGGAGG GTAA

GGGTAATGACGTGAATGCAAAGCGAATCAAGGATTATCGTCACAAAGTTGAGACAGA GCTG

TCTAGAATCTGTGGAGACATTTTAACCATTATTGATGAACATCTTATTCCATCTTCT AGCTCTG

GAGAGTCTATGGTCTTCTATTACAAGATGAAAGGAGATTACTATCGTTATCTTGCTG AATTTA

AAAGTGGTAGTGATAGGAAAGAAACTGCTGATCAGGCCCTCAAAGCATACCTGGCTG CTTC

AACCACTGCAACAACAGATTTGCCTCCAACTCATCCCATCAGGCTTGGCCTTATTCT GAATTT

CTCAGTGTTCTATTATGAAATTCTTAACTCTCCTGAGAGAGCATGTCACTTGGCCAA ACAAGC

GTTTGATGAAGCAATTGCAGAACTTGATTCTCTTAGTGAAGAGTCGTACAAGGATAG CACAT

TAATAATGCAGCTACTAAGAGACAATCTTACCCTTTGGACTTCAGATTTGCAAGAAG ATGGA

GGAGAAGAGCAGCTCAAAGGTGAAGAGATTAAGCCAGAAGATGGAGAGCATTAACAC TAAA

AGGGGAGCAGAACGAGTTTATGCATGAGAAGCTATGATCCCATGGTTATTAGGGTGT AGGT

CATTATTTAATTGGTAGTTCTTTCACATTTTCTGCTGCTTTGGAGATGTAGATATTA CTTCAGC

CCATTTGGTTATATGGGATTGAATTTTAGCTGATTTGGCATTGGACTTGTTTAGCTA TATAGG

TTCAGATGTATAAAACTTTCTATTCTGGGATCTAGGTTTTTTCGGCTGGAACTCGGG TGTATC

TCTTTGGGGATTAAATCTGCATCCGMGGTGTTGTCCAATTTTAAAACAAAGACCACA TCGTA

TAGTTTATATATTTGMTGTGATTACTGTTGMGCATCAAAAMAMAAAAMMAAAAAAAM AAλAAfiλAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

100 GGGTATATAGAGGAAAAGGCAAGCTTTCTGTTTCAAAGGGAAGATGAGTTCAAGGGAGAG A

AAAGCGAGGGTGGGTTTGAAGCTGCCAATCCCAGCTCGGGAAGACGCATTTGCTAAA CCAA

TGCCATTGCCGCTTCCACTGCCGAAGCCTCCTAACATGAATGGTGCCTGCAAGTTGC CCTG

CGTTCCTCTTGAAGAAGTTACACTGGAAGATCTCCAGAAGATTTCAACTTTGGGGTG TGGGA

GCAGTGGTAAAGTGTACAAGGTTAAGCATGCCAAGACTGGGAAAATTTATGCCCTCA AAATC

ATTCAGGAAAAGCACGAGCTTGCTGTCCGAAAGCAAATAATGAGGGAAATGGAGATT CTCC

GAAGGGCGAATTCTCCACACATCGTGCAGTGTTATGGCATATTCGATCGAGGAGGAG AGAT

CTCGTTTGTGTTGGAGTACATGGACGGTGGAACCCTTGCGCAGGTTCTTCAAGCCCA CAAG

AAAATCCCAGAACACTATTTGGCTGAGGTTGCCAGACAGGTGCTGAAGGGCTTGCAT TACC

TGCACCAGAACAAAATTGTTCACCGTGATATAAAGCCCTCCAATTTGCTGATCAACA AGAGA

AGAGAAGTGAAGATTGCCGATTTCGGTGTCAGCACTGTGTTGGCTCACACTTTGGCC CAGT

GTAATTCCTTCGTGGGTACTTGTGCTTATATGAGTCCTGAAAGGTTCGATCCTGATG GGTAC

GGTGGAAAGTATGATGGATGCTCTGCAGATATATGGAGCTTGGGATTATCTTTGCTG GAATG

TGCGCTTGGAAGGTTCCCTTGTTTGTCTCCGGGGCAGAGGCCTGATTGGCCTACTTT AATG

GTGGCCATCTGTTTGGGCGACCCTCCATCCCCGCCACCTGATGCATCGCCAGAGTTT CAGA

GTTTTATCAGATGTTGCCTTCAAAAGGATGCGTTACTTCGCCATACTGCACATCGGC TGCTT

TCGCATCCTTTTTTGAAGAAGTATGAACAGCAATCTTGTGACCTGGCTCCCCTCCTG CAGTC

TTTACACTTGTAGAATTTTGAATTCCTTTTTGTATTTTGAATATTGTACCTGAGAGC ATTCATT

GACTTGTAATGAATGTACACTCTCTTGGTCTCTGGAACTCTATTTTGTAAATCATTT TGCAAT

GCAACTGCAGTCTTCTTTACAAAAAAAAAA

101 AAAAGGTTTCCATCTAGACCGTCCATACCCTCACAGGGACGACGCACGGGGTGACGTGGA A

CACCTGGTTCGGCTGACACGTGTCAGCMTGTTCATAGCATGACCGGCTACAAAAGGG ACT

CATTGATCTTTCAGAAGAATTGAGCTTTTCTTATTGGGGAGCGAGAGGTGAATTCGT TCACA

AATCATCGTCTGGTCTGCGATTGGACTTTTGCGATCATTAAATTGTCAGCTACGGAT CTTCGT

TCTCACTCCTCTGTTGATCCAAAAGCTGCGGAGCCCGGCAATCTGCAGAAATTTTTT TGAAG

AATTTGAGTTTTTGAGACCGGCTATCTGCAGAGAAAAATTCGAAGAATTTGAGTGCC AGCAT

CGAATCCCCGGACTGAATGGCGACCACTGGCACCAATAACATGCAGGCTAAGCTGGT GCTT

CTTGGTGATATGGGTACTGGAAAATCGAGCCTTGTTTTGCGATTTGTCAAAGGCCAA TTTTT

GGATTATCAGGAGTCGACAATTGGAGCAGCATTTTTCTCACAGACACTAGCAGTGAA TGAGG

TGACTGTAAAATTTGAGATATGGGACACTGCAGGACAGGAAAGATATCATAGCTTGG CGCC

CATGTATTATAGGGGTGCGGCAGCAGCTATAATTGTTTATGACATAACAAATTTGGA TTCTTT

TGTCCGAGCAAAGAATTGGGTGCTGGAGCTTCAAAAACAAGGGAACCCAAATTTGGT TATG

GCCCTTGCTGGAAATAAGGCTGATATGGCAGCAAAGAGGAAGGTCGAACCAGAGGAA GCT

GAAACATATGCAAAGGAMATGGTCTATTTTTCATGGAAACCTCAGCAAAGACGGCGC AGAA

TGTCMTGMCTGTTCTATGAMTTGCGCGMGATTACCTAMGCCCGACCAGTGCAGCAGC

CTGCAGGCATGGTTCTCACAGATAGACCTGCAGAGAGTGCTAAMCTTACTCTTGCTG CTCA

TMGCCCTCGATTTCGTGTCACTGAAAATTTGMGATGCCACCTTCAGCTGTAAGCAGT TATT

CTATGCACATTATTTGCTACGGCTGTGATATCCGGAGGAGATGGTGGGGGGGGGTTC MGC

TTTGTTTAGAACTTGCTTTMGGMTTTTAGCGTTTATGGAGAMTGTAMMTACATATTT TG

GTGCTTAMTTATATCTCTGTAGTGAGTTGCGATGGTCATTGAAAGCCTTCTGATACM CTCT

TTGGTGCCATTTATGATGAGCTTATATTTAMTTGMMGCTGtGCTCTGTTTAAATACT CCG

AGCTCGGAGAGGGTAGATCTCTTTTGATCCTGCMTGACCTCTTGTGTTTGATTGATT GTAC

TAGACTATACTATGGGACGCCTMCCTGTCATTTAAAMTGTGAGACTGTTCGTMCMAG TC

TTGCTATTGCTACCTTGCATTGAMCTAATGTTTTCTTGMGCATGATGAATAMTTGGC TAAT

AGTGTAGTCGTTCTGMGMMMAAMTTCTTCMTGGTAGMTTGGATATTTGTGATCTTT

GMCTTGGMTTGATATGATCAGTCATTGTGTATTATATTTCTTTCTCAGAGGATGATM TCG

GTTGAATTTGAATATAMTCTCTCC

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

102 GAAAGAAGAAGAGTACAACATCACAAAλGGCCAAAGAGCAGGTCGAGGCTGCTCCCACT GA

AATCTTTCGCCATTCGACTGTTAGAAAGCACAACAAAGCAGTCGTCAGCTTTTGAAT ACCAAT

TCCGTGGGCGATCGGAATCCTCCCTGCCCCTGCATCCTTTCGGCAGCTCGCGGAATA ACAA

GCCTCTGCAGGTTTGGGGTTCTTGGATGCAGAATTAGAAGACAGCGCCATGGAAACG GGC

GCTGCGGCAGTAGACGGTCACATACAGGGAATTCTGACCCATGGCGGTCAGTATGTG CAGT

ATAATATATTTGGGAACCTCTTCGAGGTCTTCTCCAAGTACATACCCCCCATACGAC CTATC

GGCCGCGGCGCATATGGCATTGTTTGCTCGGCAGTGAACTCGGAGACAAATGAGGAA GTT

GCAATTAAGAAAATTGGCAATGCTTTTGATAACAGAATTGATGCAAAGAGGACTCTT CGCGA

AATTAAGCTTCTATGCCATATGGAACATGAAAATATCATTGCAATTAAAGACATCAT TCGGCC

ACCTCAGAGAGAAATTTTTAATGATGTTTATATTGTATATGAGCTCATGGATACAGA TCTCTA

CCAGATTATACGCTCCACTCAACCATTAACAGAGGATCACTGTCAGTACTTCCTATA TCAACT

ATTGAGAGGGCTGAAGTACATACACTCAGCAAACATTCTGCATAGAGATTTAAAACC CAGTA

ATTTGCTTCTAAATGCAAACTGTGACCTAAAAATATGTGATTTTGGGCTTGCACGGA CTACTT

CAGAAACGGACTTTATGACAGAGTATGTTGTTACTCGCTGGTATCGTGCACCGGAAC TACTA

TTGAATTGTTCCGAGTATACAGCAGCCATTGATATCTGGTCAGTGGGCTGCATTTTT ATGGA

GATACTAAAGCGGGAGCCCTTGTTTCCTGGTAAAGATTATGTTCAGCAATTAAGGCT CATCA

CTGAGTTAATTGGTTCACCAGATGACTCTGATCTTGGCTTTTTACGGAGTGACAATG CTAGA

AGATACATCAGGCAACTTCCACAGTTTCCTAAGCAACCTTTTTCTCAGAAATTCCCC AACATG

GCTCCAGCAGCTGTAGATTTACTTGAAAAAATGCTTGTATTTGATCCAAGCAAACGC ATTACA

GTTCAAGAGGCCTTGAGTCACCCTTACTTGGCAAGTCTGCATGACATCAATGATGAA CCCAG

CTGCCCCACTCCTTTCAACTTTGATTTTGAGCAGCCCTCATTCACCGAGGAACATAT AAAAG

AGCTCATTTGGAGGGAATCTCTTAACTTCAACCCAGACATGATGCAATAGCTGGAGC AGATG

GGCTTGATATTTATCTTGTAATTCCTCQTTACTGGTTATGTTATTATGCTTCTGCAA GGCAATC

CTTCTCTTGGTTTGTTATTGCCTTCTGAAGGTTTGCAGATCATTGTGCAGGTGTGGA AACTTG

TTTTATTAGAGTTAGGTTTGCTTTTATTCTTTGAAGGTCTGGTAAAAGAAAAGGAAT TGATGG

ATATGCTTACAGATCATTGTGAAAATTGTGTATTCCTAATCTGAGCCAACTATTGGC CTCTAC

TTTATTATCATTGGACATTAAAATGTAACTGGGAAACTTAATAATCTAAAGTAAATG CTGAAG

GAATTTGTTAAAAAAAAAA _ ^ _

103 GGTTTTAAAATCGTGGCATATGCGGGTGACAGAACAACCAGAAGATTACCTCTTCAAAAT TG

TTTTAATAGGCGACTCTGCTGTGGGAAAATCCAATCTACTTGCAAGATATGCCCGGA ACGAG

TTCTATCCCAATTCCAAATCCACGATCGGAGTGGAGTTTCAGACACAGACCATGGAA ATCGA

TGGTAAAGAGATCAAAGCACAGATCTGGGACACGGCCGGCCAGGAGCGCTTCAGGGC CGT

GACCTCGGCATATTACAGAGGAGCCGTGGGAGCTCTTGTCGTGTATGACATCAGTCG GCGC

CAGACATTCGACAATATTTCTCGGTGGCTCGATGAGCTGCACACGCATTCTGATATG AATGT

GGTTACAGTAATAGTTGGCAACAAAACCGACCTAATGGATGCCAGAGAAGTTTCTAC AGAAG

AAGGAGCAGCATTGGCAGAGGCTCAGAACTTATATTTTGTAGAGACCTCAGCACTGG ATTCT

ACAAATGTCCAAGTAGCTTTTCAAACAGTTGTCAAAGAAATTTACAACATTCTGAGT AGGAAA

GTATTGTCATGTCAGGAACAGAAACTTGAATCAAAATTAACTAATGGAAAAACAGTC ATTTTG

CATGAAGCAGAAAGTGAATCTACCACGAAACAAACTGGAAAGTTCTGGTGTTGTTCT GGTTA

GCTTTGTTTATTTCAATACTTTCCAAGGGGTTCGCAAGGTCTTTTGCAATGTCTAGC CAGATT

ATTCCATGTGAAAGAATTCTTAAAAGTGTGATGCGG

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

104 CTGAATGGTGTTTTTCGGATCTTAAACATAAATTCATTATCAACTGCATTTCAAAAGCTC GGT

TTCTTCCGTAGTATTCTTGCCTCCGTCGAGGCCTGMTGGGTCGATTGTGGTTATTGA AGAT

ACATTTTAGGTTTTAAAATGATGTCATATGCGGGTGAAGAACAACCAGAAGATTACC TCTTCA

AAATTGTTTTAATAGGCGACTCTGCTGTGGGAAAATCCAATCTACTTGCAAGATATG CCCGG

AACGAGTTCTATCCCAATTCCAAATCCACGATCGGAGTGGAGTTTCAGACACAGACC ATGGA

AATCGATGGTAAAGAGATCAAAGCACAGATCTGGGACACGGCCGGCCAGGAGCGCTT CAG

GGCCGTGACCTCGGCATATTACAGAGGAGCCGTGGGAGCTCTTGTCGTGTATGACAT CAGT

CGGCGCCAGACATTCGACAATATTTCTCGGTGGCTCGATGAGCTGCACACGCATTCT GATA

TGAATGTGGTTACAGTAATAGTTGGCAACAAAACCGACCTAATGGATGCCAGAGAAG TTTCT

ACAGAAGAAGGAGCAGCATTGGCAGAGGCTCAGAACTTATATTTTGTAGAGACCTCA GCAC

TGGATTCTACAAATGTCCAAGTAGCTTTTCAAACAGTTGTCAAAGAAATTTACAACA TTCTGA

GTAGGAAAGTATTGTCATGTCAGGAACAGAAACTTGAATCAAAATTAACTAATGGAA AAACA

GTCATTTTGCATGAAGCAGAAAGTGAATCTACCACGAAACAAACTGGAAAGTTCTGG TGTTG

TTCTGGTTAGCTTTGTTTATTTCAATACTTTCCAAGGGGTTCGCAAGGTCTTTTGCA ATGTCT

AGCCAGATTATTCCATGTGAAAGAATTCTTAAAAGTGTGATGCGGTAGGAAGTTTTG CTCTA

CTACTGGTTATACAGCAGCTTGAAACAAAACTTGGGAATTCTCATTTTTGGCTGGTT TTGAAG

CAATTTCAGATTGAAGGGAAATGCTGATTCATAGCAAAAAAAAAA

105 ACACGAAAAACCAAAAGGTTGCTCTAACATTGAATGAAAATCCATTGCTCAACTGCTCAT TTA

AATGAGGATGCATCACACTACTGTGCCTGATCTGTATCGGGAACCCATTTGAGTAGA TTTGA

AATATACATAACTAACCCATTTGAGTAGATTTGAAATATACATAACTAGCGACAAGT CAAATC

TCGTTATCTTCTGACCATCTTCTCGATTTCCCTGAAGGAAGCTTGGATTATGGCGAC TCGGA

AACGGACATTGCTGAAGGTCATCATTCTGGGCGATAGCGGGGTGGGGAAAACATCAC TAAT

GAATCAATATGTGAATAAGAAATTCAGCAACCAATACAAGGCAACAATTGGAGCAGA TTTCC

TGACCAAAGAAGTGCAAGTGGAAGACAGACTTGTGACAATGCAGATCTGGGATACAG CTGG

GCAGGAGCGTTTTCAGAGTTTAGGTGTTGCCTTTTATCGGGGTGCAGACTGTTGTGT CCTTG

TCTATGATGTGAATGTTATAAAATCATTTGATAATCTGGACAACTGGCACCAGGAAT TCCTTA

TACAGGCAAATCCTAATGATCCAGATAATTTCCCATTTGTGGTATTGGGAAATAAAA CTGATG

TTGATGGTGGTCATAGCAGAGTAGTGTCTGAGAAGAAGGCAAAGATGTGGTGTGCAG CCAA

AGGAAACATTCCATATTTTGAAACATCAGCTAAAGAGGACATGAATGTGGAGGAAGC TTTTC

AGTGCATTGCTAAGAATGCATTAAAAAATGAGCCAGATGAGGAAATTTATCTGCCAG AGACT

ATAGATGTGGGTCACATCGGTGTACAGAGGCCATCTGCATGCCAGTGTTGAAGATCC ATGA

GTAAATGAGGTAAATATGGACAAGGTGCCAGATAATTTTTACATGTCTAGCTGGTTG GTAAC

AATGGTATTATTCTTGTACCAGAATGTGAAATTTTTGGTAATTCTTGATTCAAGAAT CAGATTG

GAGAAACTTATATATGGTTTGGATTCTGGAATATTCATTATAATGGGACCTATGCAC TAAGAT

TGAATATTCCCCTTCAAGAGAGTTAAGGGATGCCTACAGTAAGTTTCTTGTGGTGAG CTAAA

ACGAAGTTGTAACTGCAGTCTTCAGAAAAGGCTGTATCAATCCGGTCTTAACCAGAC AGCTC

AAAAGTGTCTGAATTAGCTTGTGTTTATTCATGCTCTCTGTATTCGTATTTTCCAAT GCATTAT

ATATGCTCTCTTGTAATAGCTACCCTGCTTTCACTTGGATACTGTTCGCTGTTAATG CTTGAA

ATTTAATATAAATTTCTCACCTCTGTTTGTCCATGACTCCAAAAAAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

106 GGTTGCTCTAACATTGAATGAMATCCATTGCTCAACTGCTCATTTAAATGAGGATGCATC AC

ACTACTGTGCCTGATCTGTATCGGGAACCCATTTGAGTAGATTTGAAATATACATAA CTAGC

GACAAGTCAAATCTCGTTATCTTCTGACCATCTTCTCGATTTCCCTGAAGATACTGG TCTGAA

ATTGAAGGAAGCTTGGGATTATGGCGACTCGGAAACGGACATTGCTGAAGGTCATCA TTCT

GGGCGATAGCGGGGTGGGGAAAACATCACTAATGAATCAATATGTGAATAAGAAATT CAGC

AACCAATACAAGGCAACAATTGGAGCAGATTTCCTGACCAAAGAAGTGCAAGTGGAA GACA

GACTTGTGACAATGCAGATCTGGGATACAGCTGGGCAGGAGCGTTTTCAGAGTTTAG GTGT

TGCCTTTTATCGGGGTGCAGACTGTTGTGTCCTTGTCTATGATGTGAATGTTATAAA ATCATT

TGATAATCTGGACAACTGGCGCCAGGAATTCCTTATACAGGCAAATCCTAATGATCC AGATA

ATTTCCCATTTGTGGTATTGGGAAATAAAACTGATGTTGATGGTGGTCATAGCAGAG TAGTG

TCTGAGAAGAAGGCAAAGATGTGGTGTGCAGCCAAAGGAAACATTCCATATTTTGAA ACATC

AGCTAAAGAGGACATGAATGTGGAGGAAGCTTTTCAGTGCATTGCTAAGAATGCATT AAAAA

ATGAGCCAGATGAGGAAATTTATCTGCCAGAGACTATAGATGTGGGTCACATCGGTG TACA

GAGGCCATCTGCATGCCAGTGTTGAAGATCCATGAGTAAATGAGGTGCCAGATAATT TTTAC

ATGTCTAGCTGGTTGGTAACAATGGTATTATTCTTGTACCAGAATGTGAAATTTTTG GTAATT

CTTGATTCAAGAATCAGATTGGAGAAACTTATATATGGTTTGGATTCGGGAATATTC ATTATA

ATGGGCCCTATGCACTAAGATTGAATATTCCCCTTCAAGAGAGTTAAGGGATGCCTC CAGTA

AGTTTTTTGTGGTGAGCTAAAACGAAGTTGTAACTGCAGTCTTCAGAAAAGGCTGTA TCAAT

CCGGTTTTACCCAGACAGCTCAAAAGTGTCTGAATTAGCTTGTGTTTATTCATGCTC TCGGTA

TTCGTATTTTCCAATGCATAATATATGCTCTCTTGTAATAGCTACCCTGCTTTCACT TGGATAC

TGTTCGCTGTTAATGCTTGAAATTTAATATAAATTTCTCCCCTCTGTTTGTCCAAAA AAAAAA

107 GCAATATTTTAAAAAAGATGAACAGTGAGATAAAATGAATAATTGCTTCTCATGAATCCG AGC

AGCTGMTTGTGCAAGGGACATGTGCTTGCTCAATATAATTTTATTATTGTTCTTCCA TAAAG

GCTCTCACGAGCCAAAAGAAACACGAAAAACCAAAAGGTTGCTCTAACATTGAATGA AAATC

CATTGCTCAACTGCTCATTTAAATGAGGATGCATCACACTACTGTGCCTGATCTGTA TCGGG

AACCCATTTGAGTAGATTTGAAATATACATAACTAACCCATTTGAGTAGATTTGAAA TATACAT

AACTAGCGACAAGTCAAATCTCGTTATCTTCTGACCATCTTCTCGATTTCCCTGAAG GTTCTC

GCATTTTCTTCTTCTCTAGGATCATTTATTAACTCAGTTGTCATCCACATTTGATTG CTGATAC

TGTGCATGGTTCTGAGAATCTCAGAATTGACAATTGGGTATGTATATACTGGTCTGA AATTGA

AGGAAGCTTGGATTATGGCGACTCGGAAACGGACATTGCTGAAGGTCATCATTCTGG GCGA

TAGCGGGGTGGGGAAAACATCACTAATGAATCAATATGTGAATAAGAAATTCAGCAA CCAAT

ACAAGGCAACAATTGGAGCAGATTTCCTGACCAAAGAAGTGCAAGTGGAAGACAGAC TTGT

GACAATGCAGATCTGGGATACAGCTGGGCAGGAGCGTTTTCAGAGTTTAGGTGTTGC CTTT

TATCGGGGTGCAGACTGTTGTGTCCTTGTCTATGATGTGAATGTTATAAAATCATTT GATAAT

CTGGACAACTGGCGCCAGGAATTCCTTATACAGGCAAATCCTAATGATCCAGATAAT TTCCC

ATTTGTGGTATTGGGAAATAAAACTGATGTTGATGGTGGTCATAGCAGAGTAGTGTC TGAGA

AGAAGGCAAAGATGTGGTGTGCAGCCAAAGGAAACATTCCATATTTTGAAACATCAG CTAAA

GAGGACATGAATGTGGAGGAAGCTTTTCAGTGCATTGCTAAGAATGCATTAAAAAAT GAGCC

AGATGAGGAAATTTATCTGCCAGAGACTATAGATGTGGGTCACATCGGTGTACAGAG GCCA

TCTGCATGCCAGTGTTGAAGATCCATGAGTAAATGAGGTAAATATGGACAAGGTGCC AGATA

ATTTTTACATGTCTAGCTGGTTGGTAACAATGGTATTATTCTTGTACCAGAATGTGA AATTTTT

GGTAATTCTTGATTCAAGAATCAGATTGGAGAAACTTATATATGGTTTGGATTCTGG AATATT

CATTATAATGGGACCTATGCACTAAGATTGAATATTCCCCTTCAAGAGAGTTAAGGG ATGCC

TACAGTAAGTTTCTTGTGGTGAGCTAAAACGAAGTTGTAACTGCAGTCTTCAGAAAA GGCTG

TATCAATCCGGTCTTAACCAGACAGCTCAAAAGTGTCTGAATTAGCTTGTGTTTATT CATGCT

CTCTGTATTCGTATTTTCCAATGCATTATATATGCTCTCTTGTAATAGCTACCCTGC TTTCACT

TGGATACTGTTCGCTGTTAATGCTTGAAATTTAATATAAATTTCTCACCTCGGTTTG TCCAAAA

GAAAAAAAAAAAAA

TABLE 2: Cell siαnalinα αenes sequences (continued)

SEQ ID NO Sequence

108 GGCGATACGAGGCAGCCAGCTTTTTACACCTGTTGATTGGAGAGCCCAAACAGAAAATAG C CAAACACCCGATGCATTCGCAGGTCGTGGGGAATTCGTGAGTGGAGGAAATCGATCCACT C TCTATATGTAAATCGCTATCACACACATCGCACTCTGCGAAAAAGGGAGAATTTTTTTCC TTC

AAAACGAGATGAAGATGGGTTAAAACGGTGGTATGTGGGCCGATCTATAGCAGAAAC TCTG

TAAAAACCCTATTGAATTTCAATGGGGCAGGGCGCCTCGTCTTCTTCCGTGGTACAT GCCTT

AAAACGCGAAGAAAACGATGTGAATTTGGGCAGAGATTACAGCCTGAGCCTTCCGGA TGAA

TGCCTGGCCTGCATCTTCTGCACTCTGAGCTCCGGCGACCGACAGCGATGCTCTCTG GTGT

GCAAGAGATGGTTTCTTGTCGAGGGTTCGAGTCGCCAGCGGCTATCCTTGGATGCCC GGTT

GGATATCTCAGCGGCAATCCCAGGCCTCTTCAGCAGGTTCGATCATGTGACCAAGCT CGCT

CTCAGGTGCGATCGCAGAATGGTAAGTATAAAAGACGAGGGCTTGATTAAAATTGGA ATTCA

TTGTAAGAGCCTTAAAAAGTTGAAATTGAAGGCCTGTAGGGAGTTATCTGATGTGGG TATCG

AGGATTTTGCTAAGCTGTGTACTGGTCTGAAAAAATTGTCGTGTGGGTCTTGTACTT TTGGG

GCAAAGGGGATGAATGCTGTTCTTAAGTATTGTGTAGGGTTAGAGGAGTTGTCTGTT AAGCG

GTTGAGGGGTTTAGCTGACGGGAGTGTCGATGTTATCGGCCCCGGGTGTGCGATGTT GAA

GAGTATTTGCCTGAAGGAACTTTTTAACGGGCAGTATTTTGGACCCCTGATTGCTGG ATCGA

AGAACCTGCGTACCCTCAAGCTGTTTCGATGTTCAGGGGATTGGGATAAGCTGCTTG AGGT

GATCACTGATCATGTGAGTGGATTGGTTGAGGTGCATCTCGAGAGGTTGCAGGTAAG CGAT

CGGGGCCTGATGGCCGTTTCGAGGTGCGCAGGATTGGAGGTCTTGCATCTGGTGAAG ACT

CCGGAGTGCACGAACGTCGGGCTTGCGGCGATCGCCAACAACTGCAAAAATCTACGG AAG

TTGCATATAGATGGTTGGAAAACGAATCGTATAGGCGATGAGGGGCTTATTGCCGTG GGGA

AAAAGTGTCAAAATTTGCAGGAGTTGGTGTTGATTGGCTTGAATCTGACTGCAACGA GCTTG

AGTCCTCTGGCTTCCAATTGCCAGGTCTTGGAGAGGTTGGCTCTCTGTGGCAGTGAG ACGA

TCGGGGATACGGAGATCTCTTGTATCGCTGCGAAATGTCTTTCTTTGAAGAAGCTGT GCATC

AAGGGTTGTCCAGTTTCGGATGATGGGATCGAGTCCTTGGTCAGTGGGTGTCCAAAG TTGG

TGAAGGTGAAGGTGAAGAAATGCAGAGGGGTTACTTGGGAGGGCGCGGAACGGTTGA GGG

CGAATAGAGGATCTTTGGCTGTTAACTTGGATACGCCGTTGCCGAATCCAGTTGTTG GTCCA

CCTTCGGGAGCTGGTGCCGCTGAAGCTAGTGCCCCTTCAACCAGCAAATCATCAATA GCCA

AGGCAAAGTTTTCTCTCTTTGCTGGAAGAAACCTTGTGGCCTGTGCTTTTCTGAGAT TGTCA

AATGGATCCGATGGAGATCATAAACGAGTGTCTGCAAATGCATGAGTTGTTTATCCT ATTGG

AAAAACAAGGCCAAGTCATGTTATTAAGCTCTGCTGGAGTTGCTTTACTGCTCATGG ATCTTT

TGGCATAGTGTTTCCTGATGCACGGTGCAGATATATGACTTGGCATCTAGATCAGGT AATAC

TAATAATGGAGCAGGAAAACATTGTTTGCAATGGGCTATTTGCGTTAAGGTTTTCTT GTGTGC

TAAGCAGTTAGTCAATCTGGCTGTTGAACATGTTCTTCCAMGAACATAAACCGCTTG TATGC

GGTGGACATCCGATGTTTGGCTTTGTCTTATTGGATGCGTCGTGGAGTTAGTTCCTT TGTCC

ATTGAACAATCTTCCTTAAGGGACTGAGTTGACTTGTTTGCAATGGAATGTGCACAG CCAGG

CTTTCAGATGAAAGCTCTGTCGGCTGTACAGGTAGGTAGTTTCTGGACAAAGTAGAT CTCTG

GGTTGTCAGCTTGAGATTCTAAGTGCAATGCAAGAGAATCTGTGAAGGGATGGAATT AATTT

GTGCAATGTTGGCAAAATAATCAATATGCATTTGTCATACATAATGTCTAAAAGAGC TCTCGT

TTCTGATAGAAACAGTATATTTGAAATGGGTATGTGTGCAGCGGCCAGCCACACTTT CAGAT

GAATCTTTCTTTGTTATACCAGTAAACAGGTATTAAGTCTAGTGAAAAAGGAGATCA CCAGAT

TTTTGTCAAATGTTTAATTAAGTCGTTTGCTGTAAGTTCTTCAGTAGATCCAATATA ATCTGCA

CAAGGTTGGAATTAAAAAAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

109 GAGTTGTCCCAGTTGGGTACACAGCCλACTCCAGCTAACGCGCAGTCCCTGCTAGGTGC CT

ACCGGATGCTGCTGACTCTGCCGTCAATTTCCCTTTTATTATATACCACTTTATTGC TTCGCA

AGATTCAGCCAAGTGGATCTGGCTACAGATTTTCTCATCTCCAAGGCTGCCAGAACT CAAAT

CTGATCGCACACGACTCTCTCCTTTGGTCATTTTTGGGGCTTTTGGGTGTTTATTGC GGACA

CCCAATGCCCAAAGATCTGGATCCAATACCCATTTCCTAGATCAGCGTAAACAACGC GTCGG

TTTGATATTCAGCGTGTATCCGTCCATTCAACGGGAGATTGGGTTTCTGCGATACAT TCGTT

GTGTATCCATCCAACAGTTATTGGGCGTCTGCAGTAGGTTGATATTCATTATCTATC CCTTGA

ACTAGCTATTGGGTTCCCGCAATAAGCCGATATTCATCGTGTATCCATTGAAAGGCT ATTATT

TTTCTGCAATAGCTTGATATCCATTGTGTATTCATCCAGCCAGATATTGGATGTCTA TATTAG

GCCGATATTCATTATCTACCCATTGAACCGGCTATTGGGTTTCTGCTATAAGGTGAA ATTAAC

TGTGCAGCTATTCATTCAGGTTTTGGATTCTTGAGCACACCCAAGAGTTCGTTTGGT GTTGT

GTGGAGATGGCTTACAAAGTCGATGATGATTATGACTATTTGTTTAAGGTGGTCCTG ATTGG

GGATTCTGGTGTCGGTAAGTCCAATTTGCTCTCCAGATTTACTAGAAATGAATTCAG CCTGG

AGTCCAAATCTACAATTGGTGTGGAGTTTGCAACACGGAGTATTAATGTTGATGGGA AAATG

ATCAAGGCCCAGATATGGGACACTGCTGGTCAGGAAAGGTACAGAGCCATCACAAGT GCAT

ATTATCGCGGTGCTGTTGGTGCGTTGTTGGTTTACGACATCACTCGACATGTCACCT TCGAA

AATGTTGAGAGGTGGCTCAAGGAGCTTCGTGATCATACCGAGCACAACATTGTGGTG ATGC

TTGTTGGTAACAAGTCCGACTTGCGCCATTTGAGGGCTGTTTCCACAGAAGATGCCC AGAC

CTTTGCAGAAAGAGAAGGGCTCTATTTCATAGAGACATCTGCACTAGAGTCCACCAA TGTGG

MAATGCTTTCAAGCAGGTGCTGACTCAAATATACAGGATCGTTAGTAAGAAGGCCCT GGAT

GTTTCGGAAGATAATGCAGCAGCTCCCGCACAAGGTCAAACAATAAACGTGAAAGAT GATGT

CACGGCAACTAAGAAAGTTGGTTGCTGTAGCACATCATAAGCAGCAGGTGAAATCCC TCAG

GATTCGGATTTCAGTTCAGATGCAGGACTATTATGTTCATTGGAAAAACTTTGACCG ATTTCT

GGAATCACTTATAGTTGAATTCGAGCAGGTTCTCATTTGGTATGATTTTAAGAGGCT TCAAAG

TTGGACTCACTTAGTAACTAGTTTTAGACGGAGAGAAGAGTGTTGTAGCCAATGGTG GGTAA

TCTGAATTGTATATCTTATTCTTGCTGTATTCTCTGCAACTTCTAGTGTCCCAGTAC TATCTTT

GTTCTAGTCAGTGGCTTCAGTTTTACATGCCATCATTTGTATCCATTATTTGATTTT ATTCTCA

CAGTGGMCAGATTTTTTTTGATCTTAGTTMTATTAAAAAAAAAAAAAAA

110 ATMTACCCGATGCCMTTGTTTATAGCACAGAGTGCTCTTCTTCCACTGCTCTCTAGCTCT C

GTGGCACACAAGGAGGAGTTTCAGAGAGGCCAGGCCAGTCTGCGGATCTGTGTTCAG ACA

AGATGAGTAGCGACMGGAGAGGGAGMTCATGTTTACATGGCCAMCTCGCTGAGCAGG C

CGAGCGATACGATGAMTGGTTGMGCCATGMGAGGGTCGCGMGCTGGACGTGGAGTT

MCTGTAGMGAMGGAATCTTCTCTCTGTTGGGTACAAAMTGTGATTGGGGCTCGGCGA

GCTTCCTGGAGMTMTGTCCTCTATTGAGCAGMGGAGGACGCGMGGGCMTGATCATA

ACGTGAMCGTATCAMGAGTATAGACAGAMGTTGMGCAGAGCTTTCTMGATTTGCCAT

GATATTATGACCATAATTGATGMCACCTTATTCCTTCCTCCMTATTGGCGAATCTAC TGTTT

TCTACTATAMATGAMGGAGACTACTACCGTTATCTGGCTGMTTCAAMCAGGAMTGAG

AGAAMGMGCCGCTGATCAGTCCTTGAMGCTTACCAGACAGCTTCMGTACTGCAGAGT

CGGATTTAGCGCCMCTCATCCMTCAGACTTGGATTGGCCTTGMCTTTTCTGTTTTCT ATT

ATGAMTMTGMTTCACCTGAMGGGCTTGTCATCTGGCCMGCMGCTTTTGATGMGCT

ATTGCAGMCTTGACACCTTGAGTGMGAGTCATACAMGATAGCACTTTMTCATGCAGC T

CTTGAGGGATMTCTTACTTTGTGGACCTCTGATCTCCAGGAAGATGGAGTTGAGGAT CAGA

CCMGGGGGATGAGCCTGTAGTTGGGATGGATGMGAGCTTTGAGCAGGTACATGTAGA AA

CAMTGMGTTGTTAGATATGGGCTTTTATGTCGGCCTCMTGTACTCTAGAGTACTCCT TTC

TGCTCTGCAGCTGCMTTTACAMTTCGCTCTATTTATCTTGTTATTGACACCTGGTTT TGTTT

ATMGTTTTAGATTGGMCAAAAGACCAGTAGGACATTATGGGGTCTTMCTTGGTGTGT ATA

CCATGGCTATTAMTGCTTCMTATGTMTAGGGGCCCAGCACTGCAGTACTGTGTAGMT T

TAGAGTCTTTCGTTGTGCATTATTATCGTTTTGMGATTMTATAGGCTTTTGATGGAT GMG

TGGCTTTGTTGCCACAMGGAGCTGMTTCTTTGAGCTTTCCTCGTTTTCTTTTTTCAA MTTT

CTGGMGTTATATCGMTCTMCTTMTAAAM

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

111 AGAGTGCTCTTCTTCCACTGCTCTCTAGCTCTCGTGGCACACAAGGAGGAGTTTCAGAGA G

GCCAGGCCAGTCTGCGGATCTGTGTTCAGACAAGATGAGTAGCGACAAGGAGAGGGA GAA

TCATGTTTACATGGCCAAACTCGCTGAGCAGGCCGAGCGATACGATGAAATGGTTGA AGCC

ATGAAGAGGGTCGCGAAGCTGGACGTGGAGTTAACTGTAGAAGAAAGGAATCTTCTC TCTG

TTGGGTACAAAAATGTGATTGGGGCTCGGCGAGCTTCCTGGAGAATAATGTCCTCTA TTGAG

CAGAAGGAGGACGCGAAGGGCAATGATCATAACGTGAAACGTATCAAAGAGTATAGA CAGA

AAGTTGAAGCAGAGCTTTCTAAGATTTGCCATGATATTATGACCATAATTGATGAAC ACCTTA

TTCCTTCCTCCMTATTGGCGAATCTACTGTTTTCTACTATAAMTGAAAGGAGACTAC TACC

GTTATCTGGCTGMTTCAMACAGGMATGAGAGAAMGMGCCGCTGATCAGTCCTTGAM

GCTTACCAGACAGCTTCAAGTACTGCAGAGTCGGATTTAGCGCCMCTCATCCMTCAG ACT

TGGATTGGCCTTGMCTTTTCTGTTTTCTATTATGAMTMTGMTTCACCTGAAAGGGCT TG

TCATCTGGCCMGCMGCTTTTGATGMGCTATTGCAGMCTTGACACCTTGAGTGMGAGT

CATACAMGATAGCACTTTMTCATGCAGCTCTTGAGGGATMTCTTACTTTGTGGACCT CTG

ATCTCCAGGMGATGGAGTTGAGGATCAGACCAAGGGGGATGAGCCTGTAGTTGGGAT GG

ATGMGAGCTTTGAGCAGGTACATGTAGAMCMATGMGTTGTTAGATATGGGCTTTTAT G

TCGGCCTCMTGTACTCTAGAGTACTCCTTTCTGCTCTGCAGCTGCAATTTACAAATT CGCTC

TATTTATCTTGTTATTGACACCTGGTTTTGTTTATAAGTTTTAGATTGGMCAAMGAC CAGTA

GGACATTATGGGGTCTTMCTTGGTGTGTATACCATGGCTATTAMTGCTTCMTATGTM TA

GGGGCCCAGCACTGCAGTACTGTGTAGAATTTAGAGTCTTTCGTTGTGCATTATTAT CGTTT

TGAAGATTMTATAGGCTTTTGATGGATGMGTGGCTTTGTTGCCACAMMMAM

112 CAGAGCTCCTATMCCCCCAATTGTGTCTCCATTTTTGCGTGCGMCCATGGCTCAAGCTCC

CAAAMTCTGTGTATCATTCTGTTCTTCATCACMGTTCCTTGTACTGCCCTTCATTGT CTTG

CGCTGCTGCTTTCACAGAAMTCCATTMCAGTTCTTGGTTCTGCCAGTTTAGTGTGTT TGTG

CATTGCAGCGGCCGTTTCTTTGMGATCCAGAGGTGAAGTTGGGTTTTTATTATTTGT GTAC

AMTGGCGGCAGCGGCGATGGTGGAGTCATCGCGGGAGGAGMTGTCTACATGGCGMGC

TGGCCGAGCAGGCGGAGCGCTACGAAGAGATGGTGGAGTTCATGGAGMAGTGACAAA AG

GCGTGGAGGTGGAGGAGCTCACAGTGGAGGAGCGGMCCTGCTATCTGTAGCCTACAA M

ACGTGATCGGTGCCCGCAGGGCCTCCTGGAGGATTATCTCCTCCATCGAGCAGAAGG AGG

AGAGCAGGGGCAATGATGAGCACGTGGTCACCATCAGGGAGTACAGAGCCAAGGTGG MG

CAGAGCTTTCCMGATCTGTGAGGGCATTCTCCGCCTCCTCGACTCCCACCTCATCCC TTCT

TCCACCGCTGCGGAGTCCMGGTTTTCTATCTCAAGATGMGGGCGATTACCATCGATA CCT

TGCCGAGTTTMGACAGGCGCCGAGAGGMGGAGGCCGCTGAGMCACTCTGCTTGCTTA

CMGTCTGCGCAGGATATTGCTGCGGCAGAGCTGGCTCCMCGCATCCTATTAGGCTAG GG

CTGGCTCTTMCTTCTCTGTATTTTACTATGAGATTTTGMTTCGCCAGACAGAGCCTG TMT

CTCGCAAMCAGGCATTTGATGAGGCMTTGCGGAGTTAGATACCTTAGGTGMGATTCT TA

CMGGACAGCACTCTCATCATGCAGCTCCTTCGTGACAATTTGACATTGTGGACCTCA GACA

TGCAGGAGGATGCTGGGGAAGAGATCAMGAGACTTCTMGCGTGAGGACGGGGAGGAG C

MTAGTGAMTGTGATMTCTTATAGTGTATTAGGATTAGGATTAGATTACCAGGCTTTC CTG

CATTGTTTGGTAMGGAGGCCTATGTGCACGATTGTGTTTATTAGATCTCATGCTCTG CAGC

ATTTAGTTGCTGTGGGTAGCATATTCTTAGTCATATTTTGTTGGCTGCGTTTATGTT GGCATT

TTATATCATCTATTTGCGMTGGTTGGAGACAGTGGCTTGGTACTGTMTATCAGATTG GTG

GAGTCTATCMCMATCTGTAGGCCCATTCTGCTTTTGTGTTCMTMTATTTTTTATTGT CTT

GATTTAAAAAAAAAAMAMMAMMA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

113 GAGAACTAAAACCAATAAAACTTGAAGCTTTAAAAGGGAACAGGTCGAGGACGAλGCCG AG

TCTTGTCCGTGAACAATGAATAAGAAACCAGATGCTTGTAGGTTATACGCCAGTCCT TAGAA

TTATTATCCCTACGATCGTGGGAAAGCTTTTCGTTCTAGCCTGGAGGAGGAGAAGTC AAGTT

ATCGTTGCTATGTCCCACGAGATTGAACACATCGCCTTGTCGCTAGAGATTTTGGCG GTGTA

GAGCCCTTTTTCCAGTCCACTCTGGTCTTATCAATTTCCATTTCTCTCTTTATCGAT ATTAAAC

GGAAGGCCACGGTATCCTCTCTTATTGAATTTCTCCGAAAATCCGGATAAGCAAAAT CCGGA

TAAAGAGCGATTCAATCATCATCCAATTGCGGCTGATAACCCAGCAGGACTAGGCTG GATTC

AAACCTCAACAGAACCAGACTCTAAAACCTGGAGGCGAACTCCACTTTGAAACAGAG TTTGA

ACCCATGGAGCGCTAGTGGACTGTTTATCTATATGTAAATGTAATTATCAGGATTGG AACCT

CAGTTGGACCAGAATCTGAAACCTTGTGATGAACTTTGCCTCGAAACAGTCGATTTG AATCC

GTTGATCTAACCTTAATAGGCTATTTGTCTATATACAATTATCAGAAGTCCTGATTA AAGAGA

AATGGATGGAATGTCTACTCGAGGTGGCAGCAATTTTGATATGTATTTGCCTAATTA TAAGCT

CGGAAAGACGCTAGGGATTGGCTCGTTTGGCAAAGTGAAGATTGCAGAACATGCATT AACA

GGACACAAAGTGGCAATAAAGATACTTAATCGCAGGAAGATTAGAAACATGGATATG GAGGA

AAAAGTGAGGCGGGAAATCAAAATATTAAGATTATTTATGCACCCTCATATCATACG TCTCTA

TGAGGTTATAGAAACTCCATCAGATATATATGTTGTGATGGAATATGTAAAGTCTGG GGACC

TCTTTGATTATATTGTTGAGAAAGGTCGATTGCAAGAGGACGAGGCCCGATGCTTTT TCCAG

CAGATTATATCAGGCGTGGAGTATTGCCACAGAAATATGATTGTTCATCGTGATCTT AAGCC

CGAAAACTTATTGCTAGATTCCAMTGCAATGTTAAGATTGCAGACTTTGGGCTTAGT AATGT

TATGCGCGATGGACATTTTCTTAAAACAAGCTGCGGCAGTCCAAATTATGCTGCCCC CGAG

GTAATATCAGGTAAATTATATGCAGGGCCAGAGGTAGATGTTTGGAGTTGCGGAGTT ATATT

ATATGCACTTCTTTGTGGAAGTTTGCCATTTGATGATGAAAACATTCCAAATCTCTT CAAGAA

AATAAAGGGTGGAATATACACACTTCCGAGTCATTTGTCATCTGGAGCAAGGGATTT GATCC

CAAGGATGCTTGTTGTCGATCCCATGAAAAGGATGACCATTCCAGAGATTCGTCAGC ATCCC

TGGTTTCTAGAGAAACTTCCACGCTATTTGGCAGTTCCCCCACCTGATACAATTCAA CAAGC

AAAAAAGATTGATGAAGAAATTCTTCAGGAGGTGATTAAAAGGAATTTTGACAGGAA CCAGT

TGGTAGAATCCCTTCGAAGCAGAATACAGAATGAGGCTACAGTTGCATATTATTTGA TGCTG

GATAATCGGAGCCGTATCTCCAATGGTTATCTTGGCTCTGAGTTTCAAGAAGCAAAG GATTG

CATACATCACTTTGTACCAACTGATCGTGCAACACCAACTGGTGATCACAGATTAAC TGGTTT

TATTAATCAGGGAAATGCCTCAAGATCCCAATTTCCTATTGAGAGGAAATGGGCTCT AGGAC

TTCAGTCTCAGGCTCATCCTCGTGAGATTATGTCAGAGGTTCTAAAGGCACTTCAAG AGCTG

GATGTCGCATGGAAAAAGATAGGACACTACAATATGAAATGTAGATGGTTTCCTGCT GTATT

AAGGAAAGTTGATTCTTCAATGAATAAATCTTTGCATGGAAACCATATTATTCAAGA CGACTC

TACAGCTGGCATCAACTGTAGATCTCCGCCAAATGTGGTCAAGTTCGAAGTGCAGCT TTACA

AAGCCAGAGAGGAGAAATATCTTCTTGATCTTCAAAGGGTACAAGGGCCACATTTCC TCTTT

CTTGACCTCTGTGCAGATTTTCTTGCACAACTTAGAGTTCTATGACATGAAAGACTT TTAGGA

ATATTTAAGGCTCAAGAGATTCTAAGGAATATAATGGTAGTTTACCAGATTATATGG TTACTA

TCAACTGTTCGATTGTTCTAGTGTGCAGTAATGAAATATTTTGTATAGTAGTATGCT CATCATA

TTCTGTTCTGAGGAGCTGAAAATGAGAGAAGATAAATGAATCACCAGTAATCCCCTT CTTGC

TGTTGTTGCAACAAGGTTTGGATTTTCATTATCCCCCAGACAGCTAAAAGTTATTTT TTTCTTC

GCAATTTATGCGATTTAAAGAAAGCTTTGTTTTTTACTCCAAAAAAAAAAAAAAAAA AAAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

114 GGTTGACMGTCGGTGCACCTTACCCTTMCGTGCTTTGCCGMTACCATCGTAGTAGTAGA

ACTAGCCGGAGGAAGGGTCGGAAACTTATGGAAGTTTAAGTTGTATTTAGAGAAAAT TTGGC

AAGGATTTTTGGATTTATMTGGTTAAATTTTAAACTTTTTAATTTTTGATGATGTTG AATCCAT

TTTCCACATGATACAAAMCTTTCTCTACCAAMTTTTGGMCTTTTACCGGATTCCCGC CAC

TTTTGACGGTCTAGGCAATTCGTCTGCCTTGTTAAACGACTTATTTACCATCTCCCA GGACG

AGTGAGAAGGTTGTATATCTCCCATGAGAAGAAGGTTGTTGGAGTTCCAGTGCATGC ACCTA

ACGTTAACCTGCGATTCCCTATTGTTTCCTATTTCCCAGGAGGAGTCAGAAGGTTGT ATATCT

CCCAGAACTTAGAAGGAGAAGGTTGTTCGAGCTCCAGTGCAACAACGATGACAATAG CCAG

GAGATGTTCTTCACTTATAGTGCGAGGAGTGCGGTCTGCTGGTTCCCGTTCATCTGC TGTTG

GATCGCCAGCTCTATCAAAACAAGCATCAACAAAGAATTCCAGAATTCAAAGATTTG GAACA

GCTGCMGTGCTTTAGA ' GGMCCTATAGCACCACCTGTCCAAGTGAAGTACACGCATCTTCT

TATTGATGGACMTTCGTTMTGCAGCTTCTGGGAAMCATTTCCMCCTTTGATCCCAGA AC

AGGGGATTTGATTGCTGATGTGGCTGMGGCGATGCAGMGATGTGGACAGAGCTGTAM G

GCTGCACGAAMGCCTTTGATGMGGCCCATGGCCAAAMTGACTGCTTATGAMGATCGT

GTATTATGTACCGGTTTGCTGACTTGCTTGAMAGCATMTGATGAGATTGCAGCTCTG GM

ACATGGGACMTGGGMGCCTTATGAGCMTCATCCTTGGTCGMGTGCCMTGGCMTAC

GGGTATTTCGTTACTATGCAGGTTGGGCAGATAAAATACATGGCCTTACMTTCCAGC TGAT

GGACCTTATCATGTTCAAACTTTACATGMCCTATTGGAGTTGCAGGTCAMTCATTCC TTGG

MTTTTCCATTGCTTTTGTTTTCTTGGAMGTGGCTCCAGCACTAGCTTGTGGGMCACT ATT

GTATTAMGAGTGCTGAGCAGACATCATTAACAGCTATTTATGCAGCAMGCTTTTCCA TGA

GGCTGGACTGCCTTCAGGAGTCCTGMTATCATTCCAGGATATGGTCGMCTGCAGGAG TT

GCMTTGCMMCACATGGATATTGATMGCTTGCCTTCACAGGATCAACTGAMCTGGTM

AGCAGTACTAGAGTTAGCTTCTMGAGCMCCTTMGCGAGTGACATTGGMCTTGGAGGG

MGTCTCCATTTATCGTATGTGMGATGCTGATGTTGACCAGGCTGTTGAGCTTGCACA CTC

TGCTCTATTTTTCMCCAGGGTCMTGCTGCTGTGCTGCATCACGMCCTATGTACATGA GA

GCATCTATGATGMTTTGTAGAAMGACAAMGCACGGTGTTTMGTCGTGTTGTTGGTGA T

CCCTTTAMAMGGCGTTGAACMGGTCCTCAGATTGACCAGATGCAGTTTAACAAMTTA T

GAGTTATATTMGGCTGGGAMGAGAGTGGTGCAAMCTTGTMCAGGGGGAGAGCAMTT

GGTACCMGGGCTTCTACATTATGCCCACAGTTTTCTCAGAAGTTCAGGATGACATGC CCAT

TGCCACTGATGAMTATTTGGCCCTATACAATCAATTTTGAMTTCMAGATATAMCGMG T

MTMAGCGGGCTMTGGTACTGATTATGGCTTGGCAGCGGGAGTCTTTACAMGAGTATG

GATACCGCAMCACTCTCACTCGTGCGTTACGTGCAGGATCMTCTGGATTMTTGCTTT CA

CATTTTTGATGCCGGTGTACCTTTTGGTGGCTATAAMTGAGTGGCACCGGMGACMMG G

GMTATATGGTCTCCAMGTTACTTACAGGTTAMGCCGTTGTGACTCCTTTGMQMTCCA

GCATGGTTGTAGGCTGTTACGTTCCTTCTMTATATTTGATGMTGCAGMCATATTTMT CC

CTTGTGCTATTGTCMGTCAGTCTACTTTGAMTAMCTCTCTATTACTAGAAATGTGTT ACCT

TCAGAGGGGTGGGATGGTTCGTTTAGCTGGGCATCCTATAGTMCGTCTCTGTAAMCT GT GTAGATTCAGACGTTAGMCTCTGGTTAGCTGTGCATCCTATAGTMCGTCTCTGTAATACG GTGTAGATTCAGACGTTGGAMTCMTTAT

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

115 GTTGGAGTTGCACACAAGGTTGGAGGAAGAAAGTTGTTGGAGCTCTCAGGTTGAACGAAA A

TGGCAGCAATGCGAGCAGGCAGGGGATTTTCTTCACTTCTAACTCGAGCAGTCCGGT CGGC

TGGTACACGGTCACCCGCCGTTGGATTGGCAGCTTTATCACAAGAAGCATCCATAAA GAATA

CTGGGATTCGAAGTTTAGGAACAGCGGCAAGTGCTTTGGAAGAACCTATAGCACCAC CTGT

CCAAGTACAGTATACACAGCTTCTTATCGATGGACAATTTGTTAATGCGGCTTCTGG AAGAA

CATTTCCAACATTGGATCCCAGAACAGGGGATTTGATTGTCGATGTGGCTGAAGGTG ATGCA

GAAGACGTGGACAGGGCTGTAAAGGCTGCACGAAAAGCCTTTGACGAGGGCCCATGG CCG

AAAATGACTGCTTATGAGAGATCATGTATTATGCTCCGGTTCGCTGACTTGCTTGAA AAGCA

TAATGACGAGATTGCAGCCTTGGAAACATGGGACAATGGGAAGCCCTATGAGCAAGC AGCC

TTGGTTGAAGTGCCAATGGTAGTGCGGCTATTTCGTTACTATGCAGGGTGGGCAGAT AAAAT

ACATGGCCTTACAGTTCCAGCTGATGGACCTTATCATTGTCAAACATTACATGAGCC TATTG

GAGTTGCAGGTCAAATCATCCCTTGGAATTTTCCACTACTTATGTTTGCTTGGAAAG TTGGTC

CTGCACTAGCTTGTGGGAACAGTATTGTATTAAAGAGTGCTGAGCAGACACCATTAA CAGCT

CTTTATGCAGCAAAACTTTTCCATGAGGCTGGACTGCCTCCAGGAGTTCTGAATGTC ATTTC

AGGATATGGTCCAACTGCGGGAGCTGCAATTGCAAGACACATGGATATTGATAAGGT TGCTT

TTACAGGTTCAACTTCTACTGGTCAAGCAGTGCTAGAGTTAGCTTCCAAGAGCAACC TTAAG

CCAGTGACATTGGAACTTGGAGGAAAGTCCCCTTTTATTGTATGCAAAGATGCTGAT GTCGA

TCAAGCCGTGGAACTCGCTCACTTTGCATTATTTTTCAATCAGGGTCAATGCTGCTG TGCTG

GATCACGAACCTTTGTACATGAGAGTATCCATGATGAGTTTGTAGAAAAAGCAAAAG CGCGG

TGTTTAAGTCGGGTTGTCGGTGATCCTTTTAGAAAAGGTGTTGAGCAGGGTCCTCAG ATTGA

TCGGGAACAGTTTAACAAGGTTATGGGTTATATCAAGTCTGGGAGGGAGAGTGGTGC AAAA

CTTGTAACAGGGGGAGACCAAATTGGTACCAAGGGCTTCTATATTATGCCTACCATC TTCTC

AGAAGTTAAGGATGACATGGGCATAGCTACTGACGAAATATTTGGTCCAGTACAGTC AATTA

TAAAATTCAAAACTTTAGACGAAGTAATAAAGCGGGCGAATGCTACTCGTTATGGCT TGGCA

GCAGGAGTGTTTACAAAGAATATAGAGACCGCGAACTCTCTTACTCGGGCATTACGT GTCG

GAACAGTTTGGGTTAATTGCTTTGACATTTTTGATGCTGGTATACCTTTTGGTGGCT ATAAAA

TGAGTGGCACTGGAAGAGAGAAGGGTATCTACAGTCTCAATAACTACTTACAGGTTA AAGCT

GTTGTCTCTCCTTTGAAGAATCCAGCCTGGTTGTAGGCTGTTAGTTCCTACAAATGG TTCTAT

TGTGTGGGGGAACATATTCAGTTCCTGATGGTCTTGTCAAGTCAGTCTAATTTGAAT TTAGCT

TTCTCTGTCAATAATTAATGTATATGACCTTCAGAGAGGTGTGATGCTCTTGTTTTC CTGTGA

ACCTTCACAGTTGTGTCTCTGTAAGATTCTGTGGTTTCAGAATTTGGAACTCAATTA TCATGG

CCATATCAAATGCGAAATGAAGGGTGTCATTGTTTCTGCCAAAAAAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

116 GCTCTTTTTAGAGCCTTGGGCAGCTTTTGGGGTGTTTTTTTTTTTCTGTGAGTGGAATTG AAG

TAGAAGTTGAAGCTGAAGCTCCCCTGGATGCTCCAGAGGCTTCACAAATATCTCAGT TTCTG

AGGCTTCACAAATATCTCAGTTTCTGGAATAGGTGGAAGAGATTGAGGTTGGTTGTT TGTAT

GTATGTACAGTAGGCTTTTGGGTTTTTTTTTGGGTTTCTGGAGTGGCTATATGGATC ATGAAG

GCAGGGGAGGAAGTGGTTTATTGGCATGTTTTGGGATCAGCCGCCATGAAGCTGGAG TGCA

TTAATGGCGGACTCGACAAATTACTGCACCTTGGGATGGAGAAAAAGGGATTTGGGA TATTT

TGGACATAAGGGATTTTTTCAATAGAAATCCCGTGAAATCCCTTGAAATCCCTTAAA ACTCCT

TGCTGATTATTTTTAGCAAATTCTCCGAGATCTCGGATCTCGACTTTACAATTATGA AGCGAC

AACACTTTCAATTGCAGCAGCAGCAGCAGCCGCAGCCGAACGGTCATGGCCGCTGCT GCA

GCACTGTTCCGGTCCATCCCAACCCGGTGTCCATGCCAGGGTCCGGGCCACCACCAC AAG

CACCAAGAACAACAGCAACAGCGCCTGCAGCGGGAGCGGCAGCAGCAGGGGGAGGTG GA

AGTTCAGGGTCTTGCAAGGGCAAGGAAGTGGTATTGAAGGATACTTGTAAGCAGGGT GTAG

GTGTGGATATGGAACTGGCTTCCATGGGTTACAGTGTGAAATCCTCTGAACTGGAAC AAGT

GGCACACAGGCTTGAGCAGCTGGAGATGATGATGTGCAACGGGCAAGAGGATGGCAT CAT

TTCCCACTTGTCGTCAGAGGCTGTGCACTATAATCCCTCGGACCTCGGTGGATGGAT TGAA

AGTATGCTCAGCGAGCTTCATGTCCCTATTCTTCCTCCAACAGATCAGCCGTTTCAG TTCCC

TCAGGCAGCAGCGGATCAATCCTCTACGGTTCGGGAAGCGAGCAATTCGGTGCCGGA ATC

ATCCACTTCGACTTCGAAGGGCACCAGATCTGTGCAGAATGTTGAACAGGACCAACA GTAC

AGATTAAATGGGTCCGGGGCCGGGTTGTTTGAGCCGCCTGAGGTCCTGGATCGATCA GAAT

TCCAGCTTCATGGCTATCCGGGCCAAGGGGGAGTACGAGATAATGGGATTGATCGCA TGTT

CGGTAACTATGGCGGCCTTTTTTCTCAAGTATTAGACGTCTCGGACCTGCTAGTCGA TGACC

CTGATGTTCTACAGGAACCACCACCACAGGAGGCTTCGCCCTCAACTCTGCTGCTGC AGAG

CTCCAGCAACTCTTCGCTTGAAGTCCAATCCGGGCAAGACCGTCTGGAAGAGGATGT TACG

GGAAGAGAGCAAAAGCGTTACCGTGTCTGCGACCCGGAGCTTTCGGAGCGAACCGTG GTA

GTAATGGGGGCAGACCCGCACGAATCCGGAGTCCGTCTCGTGCACACGCTGATGGCC TGC

GCAGAAGCGGTGCAGCGCGGTAATTTGGCCATCGCGCGGGAAATGGTGAAAGAAGTG AGA

ATTCTGGCTTCAGCACAGGGCGGGGCAATGAGCAAGGTCGCCACATATTTTGCCGAG GCTC

TTGCCCGGCGAATCTATGGGTTTCTCCCTCAGGACACCTTGCGGTTCAACCAGAACG ACCC

CTTGTCCGATTTTCTGCAATTTCATTTCTACCAAACCTGCCCCTATCTCAAATTCGC GCACTT

CATAGCCAACCAGGCCATTCTGGATGCCTTCTCCGGGCACCAACAGGTTCATGTCAT AGATT

TCAATCTGAAACAGGGGATCCAGTGGCCGGCCTTGATACAGGCACTGGCTCTTCGCC CCG

GCGGGCCACCGGCTTTCAGGCTAACCGGAATCGGCCCACCCCAACCCGACGGAACCG ATG

CATTGCAGGAGGTCGGCACGAGGCTCCACCAATTTGCAGAGTCCGTCAATGTAAAAT TCTC

CTTCCGTGGCTATGTTGCCACAAGCCTCGCCGACATCAAGCCATGGATGCTCGACGC CCGG

CCCGAGCTCGAGGCTGTTGCAGTGAATTCTATCCTTGAGCTCCATCGTCTCCTGGAG GACC

CCATCCCCGGACGACCCAGTGCCATCGATCGAGTACTCGCTTCCATCTGGAGCCTGA AGCC

CAAGATCTTGACAGTGGTTGAACAGGAGGCCGACCACAACCGCCCTGTTTTCTTGGA TCGA

TTCACAGAGGCACTGCATTATTATTCCACAGTTTTTGATTCCCTGGAGGCGCGCGGG TTGCA

GGCCCAGAGCGAAGAGCAGGTGATGTCGGAAGTCTATCTGGGTCGAGAAATTTGCAA CATT

GTAGCCTGTGAGCGATCGGAACGGGTGGAAAGGCACGAACCTCTCTTGAATTGGAGC GTTC

GCTTGAGAAACGCTGGCTTCTGGCCTATTCCTTTGGGATCCAATGCTTTCAAGCAGG CCAG

CATGTTGCTCAGTCTCTTCTCAGGTGGAGAAGGATATAGGGTTGAGGAGAATAATGG GTGT

CTAACACTTGGTTGGCACAGTAGACCTCTAATTGCTGCTTCTGCCTGGCAACGCTGT TAATC

ATCTATCTCACACCATCAAGAAGGTGATAGGTGGATCAAATACCCAGCAATTATTAT TGCAG

CAGCATCATCGTTTCAGGGAACCCACAACAGCCCAATTCAATTCCGGATCAGGTCAG CTAAA

GCAAAATTAACGAGTCCGTAGATTACCTACCAGCGCCGAGAATCTATTCATGTGTAT CATAC

TGAAGTTCTTGAGTTATTATAAGCAAAATTAGATTACACTTATTATTAGCTCGACTC AGTGCC

CTGTACGACTTCATAAATCACTGAGCGATATAATTTGTAATCTCTCAAACACTTTGA ACTTCA

AATGTCAGAAGCATTGAATCTCACACGGCCTATATCATAAGTAAGTTATTATTGCTC ACAGAG

ATCTCTGCCAATGTTGCATCGTCCTGATGTAATCAAGAGAATTGAATGCCAAGCAAC TTCCC

ATCATCAATTCTTTTAATTCTCAGTGATTCAGTGCATGATATTAGATTTTTCATTTA CTTCTCTT

GAATATGAAATTCCTAATTAATGTGGGAATTACCTTCACCGATTTTGCTGAAAAAAA AAAAAA

AA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

117 CCCACCTCGTACACACATAAAAATAAAGGGCAGTGAGTTGAACCTGCCACAGCGTATAAG C

AATAGCACTGAAAATGAATAAAAATTAAGGCACAGCCTTCTGTTAGCGCCCTACCCA AGTGA

CCATCCTTGCCCGAGTCTAGCCGCGTGGAAATTTTTTTGAAGCCTCTATCCACCAAT TTGTG

CACCCTGTTACAACTCGCCAGTATAGGTCTAAATCTGCATTTACACAACCCACTGGG CTTCT

TGCATCAATTCAGACAGGTTTTTGGGTGGCAAAATATTGGGAAATGGCTTATTCAGG CAGGG

CTCGGCGTCCCATCTCCTTCCTTCTGAAGCAGTTGAAGACATCCCACTCATATTCTT CGTGG

ACTCGCTGTAATGGATTTAATGGGCAGTCCATGTTTCAGTCAAATGCCATCAGCAGG TGCAA

GGCACCATCATTCAGGCCTACTGCTGAGTTGGGATGGGTTTTGGGTTTTAGCCATTC GTGC

AGAGGGTACAGCGCTGAAGTGGGTTCCACAGAGCAAGTGGGTCTAATTAAACAACTG AGAG

AAAGGACAAGTGCACCTATGAAGGATGTCAAAGCTGCTCTTGTCGATTGCAACTGGG ATCTC

GAGGCTGCATATACAGAATTGAGGAAGAAGGGTATTGCAGGTGCATCAAAAAAAGGG GCCC

GTATTGCTGCTGAAGGGATACTGGCATTGGCTCAAGATGAGAAAGTGGCTGCTGTTA TTGAA

CTAAACTGCGAGACAGATTTTGTCGCCAGGAATGAAATATTCCAATATCTGGCACAT TCTGT

GGCAAAGTCAGCATTGACCATGGAGGCCTTACCTGAACTTCTATCAGAATCTGCGAC ATTAG

ATCTAAAGCTCCTAGGGGAAATGAACATTATCTTAGATCATCCTAAACTAACTAGGG AGATAA

CTGTTCAAGATGCAATTATGGAAGTGGCTGCTATCATGGGAGAGAATGTGAAGCTTC GAAGA

GGTTTTGCTTTGTCCTCTGCAMTGGCGTTGTTTCCTCGTATCTTCATACTTCTCCGC AACCA

GGGCTTGGTCGCATAGCTGGCCTGTTGACATTAGAATCTGAAAATGGGGGTGCACCA ACAG

AAGTGCTTCAAAGGGTGGGCTCAAATCTTGCAATGCATGTTGTTGCAGCTAGGCCTT TGTTT

CTCTCAAAGGATCATGTTGCAACTAAAACATTAGAGGCTGAGCGTGATATCCTCAAA ACTCA

GGCTGCTGCGTCTGGAAAACCTCAAGCTGCTATAGAGAAAATGGTAGAAGGACAGTT AAGG

AAGTTTGTGGAGGAAATTGCACTTTTGGAACAGAAGTTTGTTATGAACGATAAAGTA AATGTC

AAGTCTGTACTTGAGGACCTATCAAAGGAGGTTGGACAACAGATCAGGGTGGGAAGT TTCC

TTCGAGTGGAGGTTGGTGAAGGCATCCACAGGCAAGAAACTTCCTTTGCTAGTGAGG TAGC

AGCTCAAGTCGGATAACTGATTACCTTTCAGATATATAATATAGTCTGACATCAATG GTAAAA

CTGAAACCTTCAAGAGTTCAGGAATGCCAATTGGCATTTGCTTATTGATGCTCGCCA GTGGC

ATTTCATAGTCCATTTACAATGAAAATGGCCGATTTTTGGACTTTAGATCTTAGTGG TTGTTC

AGTGACTTTGAAAGAGTGATAGCATTTACATTGTTTTGAATGTAGTAGTATATACTA TATTCAA

ATTGTTTCTCATGGAGCACAGAAGAGTAGATTGCCTCAGGTTAAGTTAAGACATGAA CCTTT

CGAGTAAATAAACCAAGCAGAGAAGCTGGCTGCAGAATGTAAGAATAAAATATATTG CTTTT

GTTCAAGTTTTGTTCCGATGCTTTATGCTGATATTGCTCAGATTTGTATGGTGGAAG TGAGC

GCTTCATTTTGGGCGGTTTTAGTCAAAACTTTATTCTACATTAAGTAGATTCAAGAC TAAGAA

TAAGAACTAGGCGAGCGCCATACCTTGCTGTGAAGGATAATATGTTATATAAGGGAG AGTCT

AA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

118 GGGAAGATCTACCCCACCTGGGATGMGGCGCCGAACCTTTCAAGGCCACCAAGGACATTC

GTCGAAGCCATTCAAATTCCCTTTTGCGATCAGAACTGTGCTGGATTCCTCCCCGTT CCTGC

TGGGTGCTGCGAAGTAGCAGAAGAAGAAGCAGCTTCTGGAGGAAAGAGAAGCAGAGG GTT

TGCGGTTTGTGGATGCAGAAGAAGAAGGCACCGCCATGGAAGCGAGCGCTGCGGCAG CTG

ATGGTCACATACAGGGAATTCTGACTCATGGTGGTCGGTATGTACAGTATAATATCT TCGGG

AACCTCTTCGAGGTTTCCTCCAAGTACGTTCCTCCGATACGACTTATCGGCCAAGGC GCATA

TGGCATTGTTTGTGCAGCAGTGAACTCAGAGACAAATGAGCAAGTTGCTATCAAGAA AATTG

GCAATTCTTTTGCGAATAGGATTGATGCAAAGAGGACTCTTCGAGAGATTAAGCTTC TATGC

CACATGGACCATGAAAATATCATTGCAATTAAAGATGTCATTCGTCCTCCTCAGAGA GAGAA

TTTTAAAGATGTTTATATTGTATATGAGCTCATGGATACGGATCTCTGCCAGATAAT ACACTC

CAAGCAACCATTATCTGTGGATCATTGTCAGTATTTTATATATCAATTATTGAGAGG GCTCAA

GTATATACACTCTGCAAATATTCTGCATAGAGATCTGAAGCCCGGTAATTTGTTTCT AAACGA

GGATTGTGACCTAAAAATAGGTGATTTTGGGCTTGCACGGACTACTTCAGACACAGA CTCTA

TGACAGAGTATGTTGTCACTCGCTGGTATCGAGCACCAGAACTACTATTGAATTGTT CAGAG

TACACAGCAGCCATTGATATCTGGTCGGTGGGTTGCATTTTCATGGAGATACTAAAG CGGGA

GCCCTTGTTTCCTGGTAGTAATTATGTCGAGCAATTAAAGCTCATCACTGAGTTTAT TGGTTC

ACCAGATGATTCTGATCTTGGCTTTTTGCGGAGTGATAATACTAGAAGATACATCAG GCAAC

TCCCACAGGTCCCTAAGCAACCTTTTGCTCAGAAATTTCCTAACATGGACGAAGATG CCCTA

GATTTACTTGAAAAAATGCTTGTATTTGATCCAAGCAAGCGTATCACAGTTGAAGAG GCTTTG

AGTCACCGTTACTTAGCAAGTCTGCATGGCATCAATGAAGAACCCAGATGCCCTGCC CCATT

CAATTTTGATTTTGAACAGGGCACGTTCACCGAGGAACACATAAAAGAGCTGATTTG GAGGG

AATCTCTTAACTTCAACCCAGACATGATGGAATAGCTGGAGTAGATGGGCTTGGTAT TTATC

TATTTGTAATCCTTCTTTGGTGGTTATGTTACTATGCTTATACTGTGCAATCCATCT GTTGGTT

TATTATCGGCCTTATGAAAGTTCGCAGATCATAGTGCAGACATGGGTGGGCTTGTTT TATTC

TTATTCTTGTTTTGCTCTTATTCTCTGAAGGTTTGGTAAAGGTAAATAATCGGATGG ATATGT

GTACTTTGCATATCCAGACAGAGATTGGAGTTGTGTATTCTAAATCGAGGCCAGCTA TTGGG

CCTTATGCGATTATTATTATTAAACATTAAAATGTAATAAGTAAATTTAATAATCTA AAGTACAT

GTCGAGGGAATTTGTAAAAAAAAAA

119 CTACAACGAAAACTCCTATATATATAGGGTGCCTCGGTCTTCGACTCCTCATCGAGTCCG CT

GTCTGTTGGAAGTATACACAGCTTGCCAGTACGCTGTTTTTCTGCTTTTCTGTTTGT GATTTA

TCAAAGATGGCAGTCCCCGTGATTGACATGAAGAAGATGTTGAATGGAGAAGAGAGG GAAG

TGACGATGGCCAAGATACAAAATGCCTGCCAAGAATGGGGCTTCTTTCAGCTTCTGA ACCAC

GGAATACCTCACGCTCTTCTCGACCGAGTGAAGGAGCTGTTCAAGGAACATTACAAA AATTC

CATGGACGCAGAATTTCAGAAGTCTGAGATTGTAGGGATGCTTGAAAGTGCTGTCTC CCAA

GGCAAGAATTTCGGTACTACGAAGATAGATGACGACTGGGAAACGGGCTTCTTCCTC CAGG

ATGAAACTTATGACACAGTGTCACCTCCTTTGCCTACCAATCTCAAAGAGACGATGA AAGAA

TTTAGTGAGGAAGTAAAGATACTCGCGGAAAGGATATTAGATATAATCTGCGAAAAT CTGGG

ACTGGAGAAAGGGTATCTGAAAGAAGCCATAGCAGGGGGCAATGGCGACGGCAAAGC CCC

TTTCTTTGGCATAAAAATGGCTCACTACCCGCCATGCCCAAGGCCAGAACTCGTCGA TGGC

CTGCGCCCCCACTTGGACGCTGGCGGAGTCATTCTGCTACTGCAAGATGATGAAGTG GGTG

GCCTTCAAGTTCTGAAGGACGGCACTTGGTTCGACGTCGAACCCATTCGACACGCAA TCGT

TATCGACATTGGCGATCAGCTGGAGGTGATGACCAATGGGAAATGCAAGAGCATGTG GCAT

CGCGTGCTTTCTAAAAAGGACGCGAATCGAATGTCGGTCGCAGCGTTTTATAACCCA TCGA

CCAATGCGGAGGTGTTTCCAGCTCCACAGCTGATCATGAAGGCGACAGAGCAGAATG GCAA

TGAAAATGACAATAATAATATGAATGCCCAAAGTGGCTATAGTTATCCGAAGTTCGT CTCAAA

AGATTATATGAAAGTCTATGGTGAGCAGAAGTTTCTCGAGAGAGAGCCGCGATTCGA GGCT

ATGAGAGCACTCTGTTCCCTGAAGTAATCTTCTTGAGGAGATACTAGCTCCCAGCAA TGCTT

CACTTTCAACTGGTTCTGGTTATAAACTTAAAGAATTAGAATTAGATTAATCTATAT AGGAAAT

AGAGCTCTTCCCTGTGTATTTTCTTATCGAGTTCCATCGCAATATTTAGGATCTTTG TATGGA

ATAGAATTAGAATAGGATACAGCAGGTTGGATATTATCCAAGTGGTTATTACTCTTT TGTAAT

CTCCACTCCCAGTAAGCGCGTTAAACTTTATTCGTACAGACTATATTCATATCGGAG GACTTT

GATGACATATCCTCTTTTAAATTGTGTAAACAGTTATGCAGACTTAATTTGAATACT TTATTGA

GATGCAACTGTGCATCCATTTCTAAGCATTAAAAAAAAAAAAAAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

120 CTCGTGCCGTGACGATGGCCAAGATACAAAATGCCTGCCλAGAATGGGGCTTCCCTCTC TT

CTCCATTCAACATCTTCTTCATGTCAATCACGGGGACTGCCATGAAGAAGATGTTGA ATGGA

GAAGAGAGGGAAGTGACGATGGCCAAGATACAAAATGCCTGCCAAGAATGGGGCTTC TTTC

AGCTTCTGAACCACGGCATACCTCACGCTCTTCTCGACCGAGTGAAGGAGCTGTTCA AGGA

ACATTACAAAAATTCCATGGACGCAGAATTTCAGAAGTCTGAGATTGTAGGGATGCT TGAAA

GTGCTACGAAAATAGATGACGACTGGGAAACGGGCTTCTTCCTCCAGGATGAAACTT ATGA

CACAGTGTCACCTCCTTTGCCTACCAATCTCAAAGAGACGATGAAAGAATTTAGTGA GGAAG

TAAAGATACTCGCGGAAAGAATATTAGATATAATCTGCGAAAATCTGGGACTGGAGA AAGGG

TATCTGAAAGAAGCCATAGCAGGGGGCAATGGCGACGGCAAAGCCCCTTTCTTTGGC ATAA

AAATGGCTCACTACCCGCCATGCCCAAGGCCAGAACTCGTCGATGGGCTGCGCCCCC ACTT

GGACGCTGGCGGAGTCATTCTGCTACTGCAAGATGATGAAGTGGGTGGCCTTCAAGT TCTC

AAGGACGGCACTTGGTTCGACGTCGAACCCATTCGACACGCAATCGTTATCGACATT GGCG

ATCAGCTGGAGGTGATGACCAATGGGAAATGCAAGAGCATGTGGCATCGCGTGCTTT CTAA

AACGGACGCGAATCGAATGTCGGTCGCAGCGTTTTATAACCCGTCGACCAATGCGGA GGTG

TTTCCAGCTCCACAGCTGATCCTGAAGGCGACAGAGCAGAATGGCAATGGAAATGAC AATA

ATAACATGAATGCTCAAAGTGGCTATAGTTATCCGAAGTTCGTCTCAAAAGATTATA TGAAAG

TCTATGGTGAGCAGAAGTTTCTCGAGAGAGAGCCGCGATTCGAGGCTATGAGAGCAC TCTG

TTCCCTGAAGTAATCTTCTCGAGGACATACTAGCTCCCAGCAATGCTTCACTTTCAA CTGGTT

CTGGTTATAAACTTATGTTCAATAAAGAATTAGAATTAGATTAATCTATATAGGAAA TAGAGCT

CTTCCCTGTGTATTTTCTTACCGAGTTCCATCGCAATATTTAGGATCTTTGTATGGA ATAGAA

TTAGAATAGGATACAGCCCGTTGGATATTATCCAAGTGGTTATTACTCTTTTGTAAT CTCCAC

TTCCCAGTAAGCGCGTTAAACTTTATTCGTACAGACTATATTCATATCGGAGGACTT TGATGA

CATATCCTCTTTTAAATTGTGTAAACAGTTATGCAGACTTAATTTGAATACTTTATT GAGATGC

AACTGTGCATCCATTTTTAAGCATTAAAAAAAAAA

121 GTAATTCTCTTTCGTTTTTCCCGTGACATACGGCAGGATTTACTCTGATTTTTCACAGGA ATT

CCCAATCTCGCGGAATTTTATTAAGCAGCCGCAGATGGTTTCTGTCGCTGTACCGTC ATGGC

CATTTCAGAGTAGCACCGACTGTTCAGCTATCGACAAGTACACGCTAAGCTCCCCAG CATAA

TTTGGAGGATTTTGTGAAGAAAAGGCGAAGATTTGGCGGAAATCACTCCAAATCTGG CCGG

ACTGAGTTCACAACGTGGAGTTGCGGGCCATTGTCAGAATGATCGGGTTTATATTTG CAGAA

CTGTTCTTACTTGGCAATTTCGGAGGTCGTCTGCTTATTTCCGTCAGAGATATAGAG AGTTTT

GACGAGACTTGGCATTCGGTTGTCGATTTCAGAGGTTTTGATTTGCTTCTTGGTTAG AGGTT

TTGATATTTGAGCTGAGTTGGGTTTTTGAGAGTAGGATGGCGAGTCCGTACGGAGAT TACGA

TCAGAGAATTGATTACATGTTTAAGGTGGTAGTGATAGGAGACTCCGCGGTTGGAAA ATCAC

AAATACTGTCTCGGTTTGCAAAGAATGAGTTCAGCTTGGACTCGAAATCAACCATTG GAGTC

GAATTCCAGACGAGGACAGTCGCTATTGATAACAAGACTATCAAGACACAAATATGG GACAC

GGCTGGTCAAGAGAGATACAGGGCAGTTACAAGTGCTTACTACAGGGGTGCTCTTGG GGCA

ATGTTGGTGTACGACATAACCAAGCGCCAAAGCTTCGACCATGTGGCCAGGTGGCTT GAGG

AGTTGAGAGGCCATGCCGACAACAATATTGTTATCATGCTGATTGGCAACAAATGTG ACCTT

CGTGATATGCGTGCTGTGCCTGAAGAAGATGCAAAAGAATTTGCACAGAGGGAAGGT CTTT

ACTTCTTTGAAACATCGGCGCTGGAGGCAATTAATGTGGAGATGGCCTTCATAACAG CTCTG

ACTGAAATTTACCGGATAGTAAGCAGAAAGGCCCTCACAGCAAATGAGGATGAAAGG AATG

GGAATGCGGCTGCATTAACTGGCACTAAAATCTCTCTATCAAGCCCAGAGCAGTCTG TGATG

GCTGTGAAGAAAAAGAGCTGTTGTTGATCATCTTTATTGTTTATCGTTTCACTCTGT TTGGCA

ATGACATGATCCCTTTTGTAAAATCGATTTGCATTTTTCAGTCATCCTAAACTGCAG GTCTAC

TTCCGAGAGTTGTTGAAACCCGTTTAGATTCTAAAATTTCGTTGCCGAAGCACATCT TTGCAT

CCATGTATTTACAGTATAAGAGATTTTCTCTGCATTCTGATTTGATATCTTGAATAT TTTACAG

CGTTTCACTGGTATCAAAATGGAAGCCCATATCTGTAATTAGTTTAGCATTTTCTCA GTCGCT

GGCTGAAGGGGTCACATACATTGCTCATTTCCACTGGCTACCAATGGAATTGCAAGA TTTCC

CCTTGAACAAAATGTCACACGTTCTCCGTTGTGAGATCCATGTGAGGAAGTTTTGCC ATCAC

AAATATTTTTATATGTATTTCATTATTTTGTTATTAAAAAAAAAAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

122 TCCAGCTTCAGTTTGGGAGTACTACCAGGGATTCACAGGCGAGCAAAATGGATCGACTGA T

CAGCGGCCAAACCACGTGCAATTCAGTCGAGAAGCAGAGCAATGGAGATTCGAACCT CGAC

TATTCAGTTTCCGATGCGGTCAGAGACAAGCTGCGGCTTATGAGAGACAGAATTGAG AAGG

AAGATCCCGCCTCCAAGGTTACAGATGATGGTACTCTTCTACGTTTCTTGTATGCTC GGGAA

TCAAATGTGGAAAAGGCTTGTGAGATGTTTGCAAAGTATAGAAAATGGAGACAGACT TATGT

ACCCCTTGGATACATCCCAGAAACAATGGTCGGCAATGAGCTCAAGCACAAATTTGT CTACA

TGCAAGGATATG ' ACAAAGTGGGAAGGCCGATAATGGTTCTTCGTCTGGCAAGGCACATTGC

TTCCCAGTCGAATATGGAGGATTTTAAACGTTTTGTTGTCTATGCCTTTGATAAAAT GTCTGC

TAGTGCTACAAAAGGACAGACAAAGTTTTCCATTATAGCAGATTTTGCTGATTGGGC ATACAA

GAATGTGAACCTTCGTGGCACTATTGCAGCTGTTCAAACCTTGCAGGACTTCTATCC AGAGC

GCTTAGGGAAGGTGTACCTTATTAATCGACCATACATATTTTGGGCAGCATGGAAGA TAGTT

TCTCCTTTTATTGACAAAGTAACAAGGCAAAAGATTGTTTTCACCGACGATAAATAT GTCAAA

GAAACATTACTGAAGGATATTGATGAAAATCAACTACCTGAAATCTATGGAGGGAAA TTACCT

TTAGTTGCAATTGATGATTGTGTTGTACCAAATTGGCCCCCAATAACCTCATTTTAG GAATCT

AGAAGAACTTTAATAGCGATGATCATATTGAAGTATATTAGTTGTTCTTTAATAGCG ATGAGC

ATATTGAGGTATATTGGTTGTTCTTTAGTGTTTATACCGAAATCATAAATTGTTCCT CAAATTT

ATTTCAACTTCTTACAAGAACAAAATTTTTAAAACAATTAAATTGTTCAATGTTAAC TATTTAGA

ATAACTTTTTAAAAAATGTTCAATGTTAACATTTTAGAATAAAAAAAAAA

123 CGCCTCGGAGGGTTTCTTTGCGCGAAGATCACAGGTCAGAATAGCCATTTGGTGAAGGGA A

TCTGTGGTTTCTTATTTCAGAGCACTGGTATCAGTGTTAGTCGTTCGGTTCACGTCA TTTTGA

GCCCAAATTTGAGGTCTTTCTGTGCGGATTCGGTAAAAAATGACGGAGAAGGAGAGA GAAA

ATCATGTTTACATGGCCAAGCTTGCCGAGCAAGCCGAGCGATACGATGAGATGGTGG ATTC

AATGAAGAAAGTTGCTAAGTTGGATGTGGAGCTTACTGTGGAAGAGAGAAACTTGCT CTCAG

TTGGCTACAAGAATGTCATTGGTGCAAGAAGAGCTTCATGGCGGATAATGTCTTCCA TTGAG

CAGAAAGAAGAGGCAAAGGGTAACGAGCTCAATGTCAAACGGATCAAGGAGTACCGT CACA

AAGTTGAAGATGAACTCAGTAGGATTTGCAACGACATTCTTACAATAATTGATGAAC ATCTCA

TTCCCTCTTCTAGCACTGGCGAGTCTACAGTTTTCTACTACAAGATGAAGGGGGATT ATTAT

CGGTATCTTGCAGMTTTAAGACAGGAAATGAAAGGAAAGAAGCTGCAGACCAATCTC TCAA

AGCTTATCAGGCTGCTTCMACACAGCGACTACAGATTTGGCACCTACCCACCCAATC AGG

CTTGGGCTGGCATTGAACTTCTCAGTTTTCTACTATGAAATTTTGMCTCGCCTGAGA GGGC

CTGCCACTTGGCCAAACMGCTTTTGATGMGCAATTGCGGAGCTTGACACTCTCAGTG AAG

AGTCATACMGGACAGCACATTMTCATGCMCTACTGAGAGACAATCTTACTCTCTGGA CT

TCAGATTTACAAGAAGAAGGAGGGGMGATCMCCCAAAGGTGMGAGGATAAGATAGAA G

AMTTGAGCACTAGTTTCAGAAGGGCAGTGTMTGACTACTTTCAGCATMCAACTGCCA TG

GCAGTTGTATGCTGGMGGTAGTTTATATTTGCTATGTTTCTTCATTCCTCCGTGCTG GTCGA

GGCGCTCTGCATAGACTAMTTGTATTCATGATTCCTGTTGCCAGTTTTTATTTTTTA TTTTGG

TGMGTGGGTTTMGTTAGGTTGGMCTTTGMGTACATTAGTGTTCTGCACTTTATATCC TA

AGTTGGAGGTCTTTTGAATTTTTAGTTCCACATGCATGGAATGTTGATGCACGATTT TCTGTT

TCGTCACTATTMGTTGATAGGMGTTTTAATTTGTMGCCATGAGTTGGCTGATTGGGC TCA

MTTTTGGACTTGCCTGCTTTATTTGAGCAGAAGTTGTGGACGTGTCTCTAMTGTMGA GG

TGMTGTATTTGACACTGGACCGTGTGGATGATGCAGATTACTAMMCCTTGCGTTATG M

AGATGCTACCTATAMATGTGGTTTGGCTGTTGGTTTTAAAAAAAAM

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

124 CAAGCGAATTTTTTGTTTATTTTAAGTGAAGTCAGATAGTGGTTTGAGCTTCGGTGCGGG ATA

CACAGATCCACGTCTGCATTGAATGCAAACAAAAATCAAGGGTGGTAACCTCGTGTG ATCCG

CGGGGAGAACCGTCAAACCACCCTCCCAAATTTTGGTCCCAGTTGTCGCTTTGATTT GATTC

GATCCAGCCGTTTTCGCTCTTCAATTCAACCTTCTTCGCGGTCGGAAAGGTTCAATT TGGAG

CAACATCGGACCAAATTGAGAAGCGTTCCAAGTTCCAGTATAAATGCGCAAGGGGAC AGCC

AACTGAATTCAAGCTCACGAGACCGTGTAGATTTGCCCTGTTGAAGTCTTGGGGGTT CTTTT

ACAAGCTTCTTCAGCAAAAATTATAATTGACTGCAGAGATGGTCAAACTGACGATGA TTGCT

CGTGTTACTGATGGTCTTCCTTTAGCGGAAGGCTTGGATGATGGGCGGGAACAAAGA GACC

TGGAATTTTATAAACAGCAGGCCAAGGCATTGTTCAAAAAATTGTCACACGGTCAAC ATGAA

CCTTCAAGGATGTCCATTGAAACTGGCCCATTTATATTTCACTATATCATTGAAGCT CGTGTT

TGTTACTTAACTATGTGTGATCGCTCTTATCCAAAGAAGCTTGCATTTCAGTACCTT GAGGAG

CTAAAAAATGAGTTTGAAAAGTTGTATCAGTCTCAAGTAGAAACTGTTGCAAGACCA TATGCT

TTTATTAAATTTGATACATTTATTCAGAAGACAAGGAAACTGTACTTGGACACACGA ACACAG

CGGAACCTTGCTAAACTAAATGATGATCTATATGAAGTTCAGCAGATAATGACACGC AATGTT

CAAGAAGTGTTGGGAGTTGGGGAGAAGCTTGATCAAGTCAGTCAGATGTCTAGTCGT CTGT

CATCAGAATCTCGGAAATATGCTGATAAAGCAAAAGATTTAAGCAGACAGGCATTTA TCAAG

AAGTGGGCACCTGTGGCCATTGTTCTGGGAGTTGTTTTTGTGCTCCTGTGGATGCGA TGGT

ATATTTGGCAGTGATTTTCTTTCAGTCATTATTACATTACCTGGGTAAGAGTGGAGT TTAGCT

GCTCAGAGGCAGATAGTAACAAGCAGGTAATATTTTTGAGGGAGGGCATTTGGGGTA GCAT

TTTGTTTTGGCTTGGTTGCTTTTTATTGAATGCAAATTCGAAATGAGGAAAGAGAGA TCTTAC

TGAGGGCAGTGACCAGTTGTATGCCGAGCTTGATTGGTACAGGTGAACGTGAAACAA GTTT

CACTATTTGATGGATGAGATGAGTAAGATTTTATTTTAGTTGTTAGAATTACAATCT TAGAGG

AAGATAATAATATTGTTCTGGTCAGATAGCTTATTCATCAGGGAGATGAAATTTTAA ATATTTA

CCTTAGGGTTTCTCTGTGATCAGTTGTCATTGGGGCCATTTTTTCTTTTTACAGTTA TTGTAAT

TATTTGTTGGTACTTGTCTAGTTATAAAACCAGTATTTGAATATTTCA

125 AAGAATTCGGCACGGCTTTTTCAAAGGGTACTACTCATTTACCCCTTCAAAATTGGCAGT TG

CAATGAACGGAGGAGTTCAGATCTCTTCATAGAAGACGCCGCAGCAGCAACCAGCAC GCAA

ACACTCCATTTAGACACCAACACTCCTTTCATTTGCCCCACGAACGAGAGTCTGTGT GCTCT

GTGGTCGAGAGAGAAGTTTTATTATTAAATGGCGAGGAGAACGGACGATGAGTATGA TTATC

TATTCAAGGTGGTCCTGATTGGAGATTCAGGAGTAGGGAAGTCCAATCTGCTCTCCA GATTC

ACGCGCAATGAATTCFGCCTCGAGTCCAAATCTACAATAGGCGTGGAGTTCGCAACT CGCA

CAGTGCAGGTTGAAGGGAAGACAATAAAAGCACAAATCTGGGATACTGCTGGCCAGG AGCG

ATACAGAGCAATTACAAGTGCCTATTACCGTGGTGCTGTTGGGGCTTTGCTCGTTTA TGATA

TTACTAAGCCTACAACTTTTGAGAATGTTGGAAGATGGTTGAAGGAGCTTAGAGACC ATGCA

GACTCCAACATAGTGATTATGCTAGTAGGTAACAAATCTGATCTAAAGCATCTACGA GGCGT

ATCAACAGAAGACGCTCAGAGTTTTGCTGAGAAAGAGGGTCTGTCATTTTTAGAGAC ATCAG

CGCTTGAAGCTACTAATGTTGAGAGGGCTTTTCAAACAATTCTGGCAGAGATACACA GGATA

ATCAGCAAGAAGGCCCTTGCCTCAGAGGAGGCTGCAGGAGCTGGCATCAGAGAAGGG AAA

ACTATTCTTGTCTCAGAGCCTGATTCTAATACAAAGAAGGCTTGTTGCTCATAGCAA GATTAT

ATAATGCCTGAAAATATGATATTAGAGCCCAATCTCATTTTTGGTGAGTTTTGGTTA GGTTTT

GTCGAATGATTACTTATAACGATATTTTGCTCATTCTTGATGGTAACTTACAGTTGC CTCTTTT

GTTTAGTATTTTGTTGCTGCAAGCTATTATTTGTTTGAGGAGCAATGGACATGACAC CTACAT

ATTTATTTAAGGTAGGGAATATTTTCAGAAGAAAAAAAAAAAAAAAAAAAAAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

126 GTTGTTTGTTGTTTGATTCTTCTGAGAGTAGGCCCTGCGTGTTCTGAGACTTTTTTGTCG TTT

TAATTTCTATTGAACTTGGCTCGTCATTTGTTCATTTTCAAGTATTGATTTGATGTA TAGGAGG

TGACAACTTCTGTAAGTTTTTAGATGGATCAGGACCAATCCATCTGCAGATTTGCAG CTCAG

AAGGGAAAAGGAGAGATTCAGTCTTCTTCATTCCCAGACGAAGTTTTGGAACATGTT TTGGT

TTTCCTGTCCTCCCAGAAGGACAGAAATTCTGTTTCCTTGGTATGCAAGGCCTGGCA CAGG

GTTGAGGCGTGGACGCGCCAGCAGGTGTTCATTGGCAACTGTTATGCTGTCTCCCCA CAGA

TTATGATAAAAAGGTTTCCCAAGATCAAGTCTGTCTCACTCAAGGGGAAGCCCAGAT TTGCA

GATTTTAATTTGGTGCCACCAAATTGGGGGGCCCATCTCACTCCATGGGTGTCGGCC ATGG

CAACTGCTTATCCATTACTTGAGAGGCTGTACTTGAAGAGGATGACTATCACAGATT ATGAT

CTCACATTGCTTGCAAATTCCTTCCTATATTTCAAGGAGCTTGTTATGGTTTGTTGT GATGGA

TTCAGCACAGGTGGCCTCGCTTCGATCGCAAGCAAATGCAGGCAATTGACCACACTT GATTT

GAATGAGGACGAGATACATGATAATGGAGAAGATTGGCTGGCTTGCTTTCCTGAGAC TTTGA

CGTCTCTAAGATCTCTTTGTTTTGATTGTTTGGAGGGCCCAGTAAATTTTGATGCAC TAGAAA

GATTAGTTGCAAGATGCCCCTCTCTGAAGAAGCTCAGGCTAAATAGAAATGTTTCTA TAGTG

CAATTACAAAGGTTGATAATAAAAGCACCACAGCTTACTCATCTAGGAACAGGCTCA TTTTTC

TATGAGTTCCAACTGGAGCAAGTAGCAGATCTTCTCGCAGCCTTCAGCAATTGTAAA CAACT

TCAATGTTTGTCAGGATTTCGTGAAGTTGTGCCAGAGTATCTACCTGCGGTATATCC AGTTT

GCTCTAATTTAACATCTCTAAACTTCAGCTATGCTGTTATTGGCAGCAGAGAGTTGG AAGGA

ATAGTCTGTCACTGTCGTAAATTGCAGCTACTCTGGGTTTTGGATTCGGTAGGAGAC AAAGG

TTTGGAGGCAGCAGCTACAACGTGCAAGGATCTGAGGGATCTCCGTGTATTTCCTGT GGAT

GCACGTGAAGACGGTGAAGGTTGTGTATCTGAACGGGGCCTTGTTGCAATCTCCGAG GGGT

GTCCAAATCTTGAGTCCATTCTATACTTTTGTCAGCGTATGACCAATAAAGCAGTTG TGACCA

TGTCGCATAACTGTTCCAAACTTGCCAGCTTTCGTCTCTGTATCATGGGTCGACACC AACCT

GATCATTTAACTGGTGAACCTATGGATGAGGGATTTGGGGCAATCGTAAGAAACTGC AAAAG

CCTAACAAGGTTGGCAGTATCCGGTCTACTCACTGACAAAGCATTTCAGTATTTTGG AGCCT

ATGGTGAAAGATTAGAGACCTTATCAGTAGCATTTGCCGGGGAAAGTGACCTCAGCA TGAA

GTATGTGCTCGATGGATGCAAGAACCTTCGGAAGCTGGAGATTAGAGACAGTCCATT TGGA

GATGTTGCCCTCTTGTCTGGTTTACATCACTATGAAAATATGCGGTTTTTGTGGATG TCTGAT

TGCAGACTCACTCTACAGGGATGCACAGAGCTGGCCAAGAAGATGCCTGGACTTAAT GTTG

AAATAATCAGAGAAAATGAATGCAATGATTCTCTTGTTGAGAAACTTTATGCTTATC GCACTG

TAGCAGGTCCACGGAAAGACATGCCGTCATTTGTAACCATCTTATAGCCACTTCACA TGAAT

TTCGTGGTTATGGCTCTGCTACATATGGGCAACCTGTTAGGGCTATCCTACTAAATT AATCAT

GCATCAATGTTACTGATGAAAAAGCCCATGTCCATAATGCCTTTACTTCACCAAAGG AGGAG

CAATAGAGCAGGCCAGGTTATTGCCATTTTACTTTGGAAACTTTCTTCAGGTTGTAG CTGCC

ACCTGAAGGGTTGGAAGAATGTACGATTCACTGATGCAGACTGCTAATTCTTGTTGC TCCCT

AAAGTTGAATCTAGTTAAATGCCAAACAATAAACTGGTGATAGAAATGCTGAAGGTG ATGAA

AGGTGGAGAATTACAGATGAATCCCTTCTGCGTGCATTGGATAGTGTTTTAAGGGAC TGAAT

GCCTCAATTGGTCTGTTTGTTTTAATTTCAAACAATTGACCTGTCTTTGATGCAATC TGTGCTT

TGACTTGAATTCAATCTGTGATTTGACTTGAATTTTATTTGCTATATGACTGATCCG GAGCTT

GTTGAGGAGGTTTGGAATTGTTCCGAGGGAAAATTTCTGAGTTTATCATGTTATACT GATTAA

TTGCTTGAATTATCAAAAAAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

127 GGAAAGAGCCCACCTGGGGCTGGCTATTTCATTCATTTTGACGTCAATTGCCGCATTACA AC

GGCAGCCGAGCAGAACGGAACGAAATCGGCAATGCAGATATCTAGCGAGCGCAGTCG ATG

GCCTGCTGCTTCCCTCCATTAGCCGGTAGACGACGACAAACCATTTCCCCTCCAAGG AATT

CCCGTCAAGAAGAAGGGCAATATTGCCGTCAAGAAGACGAGCAATTTCCCCTTCAAG GAAT

TTCCATCAGAATTCAGCCCTGGGGGACAATTGGAGGCTCAGGACGGACAGCGGTTTC GTAA

TCCGCAGCAGAGGTAGATGGGGTAAATGCGGTTAACCGGATTCCGGTGGCCTCAGCT CAA

CTCATGAAAAATTTCAGTCGGATCTGATCTTTCTTTTTTTCTTTTTTCTCCCTAGAT TTTTGTCA

CTCGAGGCCGATTCAAAGGGCGTCGTAGCTTTGGAGATCTCGAGCGTTCGAGATATC GAAC

CCGAGCGGCAGCGATGCAGCAGGACCAGAGGCGAAAGAACTCTTCTGAGATAGAATT TTTC

ACAGAGTATGGAGGGGCTAGTCGCTACAAGATTCAGGAGGTGATTGGCAAAGGAAGC TATG

GTGTTGTATGCTCAGCAATTGATACACATACAGGGGAGAAAGTTGCAATTAAGAAGA TAACC

AATATTTTTGAGCATTTGTCTGATGCAACCCGGATTCTACGGGAAATCAAACTTCTC AGGTTG

CTGCGCCATCCTGACATTGTAGAAATCAAGCATATCATGCTACCTCCCTCACAGAGA GAATT

CAAAGACATTTATGTGGTATTTGAACTTATGGAGTCTGACCTACACCAGGTTATAAA GGCTAA

TGATGACTTGACACCAGAACATTATCAGTTCTTCCTGTACCAACTTCTTCGAGCATT AAAATA

CATACACACAGCAAATGTGTTTCATCGGGATCTCAAGCCAAAGAATGTCCTTGCCAA TGCGG

ACTGCAAGCTCAAAATTTGTGACTTTGGCTTAGCAAGAGTTGCCTTCAATGACACTC CTACA

GCAATCTTCTGGACTGATTATGTTGCTACACGATGGTATCGGGCTCCTGAGTTATGT GGTTC

ATTTTTCTCAAAGTATACTCCTGCCATTGATATTTGGAGTATTGGTTGCATATTTGC TGAAGT

CTTGACTGGAAAGCCGCTTTTCCCAGGCAAAAATGTTGTTCATCAGCTAGATTTGAT GACGG

ATCTTCTTGGCACTCCTTCCCCAGAAACAATTGCAAGGGTTCGTAATGAAAAAGCTA GAAGA

TACTTGAATAGCATGCGCAAGAAACAACCTGTACCTTTTACACAAAAATTTGTGGGT GCAGA

TCATTTAGCACTTAAACTTTTGGAAAGATTGCTTGCGTTTGATCCGAAGGATCGTCC TACTGC

AGAAGAGGCTTTGGCCGATCCTTATTTTAGGGGGTTAGCAAAAGTAGCCCGAGAGCC TGTA

GCTCAGCCAATAACTAAAATGGAGTTCGAGTTTGAGAGACGGAGGGTTACAAAAGAT GATGT

GAGAGAACTTATTTATCGTGAAATACTTGAATATCATCCGCAGATAATGAAAGAATA CCTGAA

TGGAACAGATCGCACAAACTTTATGTATCCTAGTGCTGTTGATCAATTTAAGAGACA GTTTGC

TCACCTGGAGGAGCACTATGGGAAAGGTGGATCAGTTCCTCCATTAGAAAGGCAGCA TGCA

TCTTTGCCAAGACCCTGTGTTGTCTATTCAAACTCTGGTGGGCCCTCATCAGAGCAG GCATC

TTCAGGTCCTTCCAGGGATCGTGCTTTAGAAGTTCGTGAAGAAGCTCCAAGGTATAG TAGAG

AAGGAGAGAAGCAGCACCAAGACAGGAGCTCCGGAAATGTGAAAGTGCCCTTGCATG CAA

GTCATAAAGTTTTGCAλGGAAGTACTGCAAAACCGGGAAAAGTAATTGGTCCTGTA TTACCC

TGTGAAAATGGAAGCATTAAAGAAGCATATAATCCAAGAAGGTTGATCAGAAATGCT GGTGT

TGCACCATCTCAGTGTCCTGCTCCAATTTATTCCTATCCAAGACGAAATTCCACAGC GAAAA

CTGAGGTTGATGATAAGAGGGAAGATGGAATTAATCAGTTTAATGTATCACAACATA AGACT

CAGTATGTTGGAATTGGTGCAGCAAGGAAAGTGGCTGCTCTTGAAAGCAGGTCATCT CATTT

GTATTAAATAAGGTGGATTATTAAATCGCGTATTTTTAACTTATCTAATATCTATTT ACTGACT

CGATTCTTTAAAAAAAAAA

IABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

128 CTTTCTTCGACATCTCCGCTCTTTAGTTAATGGGTCTCTCATTTCCTGAACGTCTAGGCA GG

CCTATCCAGAATAAACTAGAGCGGAATATCATCTTTTGCTTTGCTGGACCGGGATGT AGAAC

TCCTGAACGGTAGCCCTCGCTGCGAATTTGATGTGCTAGGATTCCTTTATTAGTTGT TGTTA

CTTAGTGCTTGAAAGTGGCTTTCCTAGGAGTATTTTCTTGTTCCAACAATCCCAGTT AGAAGG

ATCATTCTACAATGAAAATTTCATCTCAGCGATATGAGAGATTGTGAAGGTATTTAA AAAACC

TCGGAGCAGCGAGACCAATCCCTCGCAAAATCCCGACCAGCAATCGAATTACGGCAA TGGC

AGACGATTTGGGAGAGTTTTACGTTAGGTACTACGTGGGTCACAAGGGCAAATTCGG CCAC

GAGTTTCTCGAGTTCGAATTCCGTCCCGACGGCAAGCTCCGCTATGCAAACAATTCG AACTA

CAAGAACGACACCATGATTCGCAAAGAGGTGTTCCTTACACAGGCTGTTCTCAGGGA ATGC

CGACGAATCATTGCCGAAAGCGAGATAATGAAGGAAGACGATAACAACTGGCCTGAG CCTG

ATAGGGTTGGACGTCAGGAGCTGGAAATAGTTATGGGGAACGAGCATATTTCCTTTA CTACT

TCCAAAATAGGATCTCTTGTTGATGTCCAAAGTAGCAAGGATCCCGAAGGCCTTCGG ATTTT

CTATTATCTTGTTCAGGACCTCAAGTGCTTTGTGTTCTCTCTCATTGGTCTTCACTT CAAAATT

AAGCCTATCTAGCCATAAATGGTGGTTGCATATACGTGCAAATGCATATTATATGAT TGAAGA

TTTACATTAAAGAGCACAATGGATCTTTTTGTACGCTAGTAGCTCCGGAAGGATTGA TTAACA

TGGATGCGAAGTTTTTTTTTTTTTTTTCCAAATATTTATTAATACTAAAGAGCATAA CATACCTT

TCTAACCGAGGAGATCCCGATGGACTGATCACGATGTGTATGTGAAGCGTGTTTTAA AACAT

TAGATTTATCGTAGTCCAGTCATTTCTATAATTTCGAGTTTTAGCTCGTCGGTTGAT TCGTTT

GTGTTCACGTGAATTTTGTGTGGCTTCTTAACTGTTGTAATTATCCGGCATTCCAAG TTGCAT

TTTTTGGTGGCGCGTTATGCTCTTGGGTCATAACACGTGGGTGA

129 CCTTGGTGTTGGGAGCACTGTCCACGGTAATCAAAATTTCATCTCAGCGATATGAGATTG TA

AAGATATTTCAAAACCCTTGGAGCAGCGATACCAATCCCTCGCAAAATAGCTGAAAT TGGTA

TTTACAAACCCTTGGAGCAGCGATACCAATCCCTCGCAAAATAGCTGAGATTGGTAT TTACA

AACCCTTGGAGCAGCGATACCAATCCCTCGCAAAATGCCCCCGACCAGCGATCGAAT TCCG

GCAATGGCAGATGATCTGGGAGAGTTTTACGTTAGGTACTACGTGGGTCACAAGGGC AAAT

TCGGCCACGAGTTTCTCGAGTTTGAATTTCGTCCCGACGGCAAGCTCCGCTATGCAA ACAAT

TCGAACTACAAGAACGACACCATGATCCGCAAAGAGGTTTTCCTTACTCAGGCTGTT CTCAG

GGAATGCCGACGGATAATTGCCGAAAGCGAGATAATGAAGGAGGACGATAACAACTG GCCT

GAGCCGGATAGGGTTGGGCGTCAGGAGCTGGAAATAGTTATGGGGAACGAGCATATT TCCT

TTACTACTTCCAAAATAGGATCTCTTGTCGATGTGCAAAGTAGCAAGGATCCCGAAG GCCTT

CGGATTTTCTATTATCTTGTTCAGGACCTCAAGTGTTTTGTGTTCTCTCTCATTGGT CTGCAC

TTCAAAATTAAGCCAATCTAGACATAAATGGTTGCATATACGTGCAGATGCATATTA TATGAT

TTGAAGATTTATATTAAAGAGCACAATGGATCTTTTTGTACGCTAGTATCTCCGGAA GGACTG

ATTAACATGGATGTGAAGTCTTTTTTCCAAATATCTATTTTGTACTAAAGAGCATAA CATGCCT

TTCTAATCGAGCAGATATTGATGGACTGAACACGATGTGTATATGGAGCGTGCTTTA AAACA

TTAGATTTATTTTACTCCAGTCATTTCTATATTTTTGAGTTTTAGCTCGTCGGTTGA TTCGTTT

GTGTTCACATGATTCTTTTGTCGCTTCTTAACTGTTGTAATTATCTGGCATTTCAAG TTACATT

TTTTGGTGGGGCGTTATGCTCGTGGGTGGATGTATACTGGTTTTTAACCTTTCTCTA AAAAAA

AAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

130 GCGCCAGTCCGGGCACGAACGACAAGAGGACCATCACCGTTTCCGTTCCGGACACGGCGG

GAGCTCCCTCTCTCCTTCCTCCATTTAAAGGGCTGAAGAGAAGTCGATCGGTGTACG TTGTT

GTCGTCAGGTTGCAGGTTCGAACCCCATACCCGCTAGCCATTGCCAGATTGCACGGC CCAC

CTGTTCGACGTGCGTGACAGTCTTCAAGTCAGGTGGCTGGTAGATTCACGATTTTCA TTTTA

AGTGCGGTGAACAGGTAAAAACGCAAAAACGCATCGCAATCATAATTCCATCGTGTT GGCAA

CCCAGCTCTCGCCGACCAGTGGGAATGACCGAAAGACTGAAGGTCTAGTTTTTGGGG TTTT

GGATAAATTTTTGCGTTTAACAGGGCGGCATTTGATTTTTCTGCTTTAAAACGGACA TTATAG

ATTGGTTCGGTTCAGTTTTCTGGATCTCCGTGCTTCGGCCCGCAGAGATCCATGATT AGAAA

TTCCGTCTCCTATATCTCCTGCTTGACGGAAACACTGGAAGTGTGAATTGACGGGAA TAAAC

GAGTCTCTAGAGTCTGCTGGTTCATGATGGGGCACAACACTTCTGAAGCCATCAAAC AGAT

GACCGCTTTCATCGATGGAGTCGACGAGCCATTGAAGAAGTCTTTCCAGACTATGCA TCGA

GGATATGCACAGCAAACTCTAGAGAGGTTTCTAAAGGCACGGGAAGGGAATGTTCAG AAAG

CAMCAAAATGTTGCTAGATTGCTTAAGTTGGAGAGTTCAAAATCACATTGATAACAT CTTAG

CGAAACCTATAGAACCAAGAGAAGTTTATAATGCTGTTCGGGAATCACAGCTCATGG GGATG

ACAGGGTACTGCAAAMGGGACGTCCTGTTTTTGCTATTGGAGTGGGGCTTAGTGGAT ATG

ACAAAGCATCTGCTGACAAATATGTGCAGTCACATATACAGATAAATGAGTACCGAG ACCAA

GTTCTCATTGCCAAATGCATCAAAGAAATATGGGAGCTACATTGGACCATGCTTGAA AATCTT

GGACATGACGGGGCTGAAACTTTCTGCTTTAAACCGCATTAAGATATTGACTACGAT AGCTA

CAGTTGATGCACCTTAATTATCCAGCAGAAGACGGAGCACATATTATATTGTTAATG CTCCAT

ATGTTTTTTCTGCCTGTTGGAAGGTTGTGAAACCCTTGTTGCAAGAAAGGACTAGAC GAAAA

GCTACAGGTGTTGCAAGGTTGTGGTAGGGAAGAGTTACTGAAGGTAATGGACTATGA TGTT

CTTCCTCATTTCAGCAGGCAGGAGGGCTCAGGGTCATCCAAACATCATAATGGCAAG ACGA

TAGATTGCTTTTCTCCAGATCATCCATTTCATGTAGAACTTTATAATTATATTAAAC AGCAAGC

AGCGATTATAAAGCCTGTTGCCCCGGAAAAAATGCGATCTTTTCATGTGGATGTTCC AGAGC

AGGATGATGAAGGAACCATTATTGTACAGACACTCAGAATCTGCATTACATAATTTA GGTGAT

GAAGAGGCAGTTGAGAATGGTGTTGCTAATTTGAATGTCAATGGGGATCAATCTCTG AGACA

CCGAAAAGCAGCTAGAAATGAGGTTCAAGGTTGAGTATGCTGAAAGTCGATTGGATA TTTAA

ATAACTGGCCCACATATCTGGAAATCTGAGTTGACAATGTGTGACATTGTGTTGTTA TCCTTC

AGTATCAGGGTTAATATTGTATACAATTCTCCAGTTTGACAATCTGATCTCAAACTG GTGTTT

TGCCTCATAATGTAATTGCATTAGATTATCTTATTTTGTGGGAGCGGTTGCCACTCC CATATT

CTGCAAAATGTCAAAAATGAAATCCTTATTTTAAAAAAAAAA

IABLE 2: Cell signaling genes sequences (continued)

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

133 CTTTGCTTTGACGGGMGACAGGTATGTTTTCTGCAAGACCCGATTTGCTTTTATGAGGGC T

TTTTTAGGCGTAATCGCTTTGTTTGGATCGCACTGGACTATAATTGTTCGGTCCTTT TCCATT

TTTTTGGCTGTTTAAGAACCCTGTTGTTCATAATATTTGTTTTCTCTTTGCCTCAAA CCCTTTC

AGCGCTTGTTTGTTTATTGGTATCAGACCTTTTTCGTGTTTGGTTTTCTAAATTAAC GTATAAA

TTCATATCGGATTGCCTCTTTTTAAATCTAATTATTGGTTTCCAATTTCTGGATTTA TAATCTTG

TTTTGGGCTGCTTTTTTATTCTGGTGGCTTGGCCTTTTCAGCATCTCTGGAGAGAAA ATGTTA

TTGGTATCTTCAGTAACCCCCATGGTAGCAAAGTCTTCCGTCTTTGCTATCTGTTCG TCATCT

GAATTCAGGGAACATCTCCTTTCTTCTATCTTCATTTAACCCTACAAGGGTTTCTGT TAATGC

AATTCAAACAAACTGTTTGAATTCCGGGGCTGGGGTTTGTTTCTTTTCCCTGTCCTT TATAGG

AAGAAAAGGAAAAATGACTGGTGTAGAATATGACGCCAGTGATAAGGACAGGGAACC CTTT

GTGGAAGTGGATCCCACTGGCAGGTATGGTCGCTATGAAGATGTGTTGGGTCGTGGT GCCA

TGAAGACGGTATACAGAGCTTTTGACCAGGAAGATGGTATTGAGGTTGCTTGGAACA AGGT

GTCTCTGCAAAATCTTGATGATGTTTCCCTTGAGAGGATCTATTCAGAAGTCCGTCT GTTGAA

GTCTCTCAGGAATGGAAACATCATTATGTTCTACAATGCCTGGTTGGATAGAAAAAC AGGGC

ATGTGAATTTCATTACCGAAGTTTGCACCTCGGGTACCCTGAGGCAGTACCGTCAGA AGCA

CCGCCATGTCTCCATGAAGGCCGTGAAGAACTGGGCACGCCAGATACTGGATGGATT GCAT

TATCTGCATAGTCATATCCCTTGCATAATTCACAGAGATTTGAATTGCAGCAACATT TTCGTG

AATGGAAATACTGGCATTCTTAAGATTGGGGATCTGGGTCTTGCTGCTGCCCTGGAA AATGA

TCATGCTGCACACACTATTATTGGTACACCAGAATTCATGGCCCCGGAATTATATGA AGAGG

ATTACAATGAGCTTGTCGATGTTTATTCCTTTGGCATGTGCTTGCTGGAGATGGTTA CTCTG

GAGATTCCTTACAGTGAGTGCCGTAGCGTTGCTCAAATTTATAAGAAGGTGAGTTCT GGTAT

AAGGCCCGCAGCACTGGAAAAAGTTACCAATCAAGAAGTGAGGCAATTTATTGAAAA ATGTC

TGGCAGTTACATCGGCAAGGCCTTCTGCTGCCGAACTTCTGAAGGACCCATTCCTCA GCGA

AGTACAATCGAGTAGCTAGTACATATGCATGTTTGAGTGCTCAATTATTTTAAGATT GAGTTG

GGGGTTTCTGCCAGCGTCTGTAGGAACTGTTGGTGGAAATATGTGATGCCAAATGCT AGGA

AAAATTATTTAGATATTATTGCATGTATCTGTGGGATTTTGATTATTTAAAATTAAG CAATTATC

GGGATTAAAAAAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

134 GACAACTTCTGCAACTCATACATTAGGAATACCGTCTTAGCAACAGCATCGGCTACCATC AT

GCCGTATTACGTGCTTCAACGAGAGGTTGAATCAGAATTTCTGGAGGTTGATCCCAC TGGTC

GCTATGGCCGGTACAATGATGTGCTTGGCAAGGGAGCATCGAAGACTGTATACAGAG CCTT

TGATGAAATAGAGGGGATTGAAGTGGCGTGGAACCAAGTGAAAGTGAATGATATTCT GCAG

TCACCTGAGGATCTGGAGAGACTTTATTCAGAGGTCCATCTTCTGAAGACTCTGAAG CACAA

GAATATCATCAAATTCTTTTCATCATGGATCGATACCACGACAAGGAACATCAACTT TATTAC

AGAGATGTTCACATCTGGTACTCTTAGGCAATATAGACAAAAACACAAACGTGTAGA CTTAA

GAGCTGTGAAGAATTGGGCTCGTCAGATCTTGAGAGGGCTTCTATACCTGCACAGCC ATGA

TCCTCCCATAATACACAGAGATTTGAAGTGTGACAACATATTTGTCAATGGGAATCA GGGGG

AAGTTAAGATTGGAGACCTTGGGCTTGCTGCAATTCTGCGTAAATCTCATTCAGCTC ACACC

GTTATCGGAACCCCGGAATTCATGGCCCCTGAGCTGTACGACGAGGAATATAATGAA TTAGT

TGACATCTATGCATTTGGGATGTGCCTATTGGAAATGCTCACCTTTGAGTATCCTTA CAGCG

AATGCTCCAACCCAGCTCAGATCTACAAGAAAGTAACATCTGGGAAAAAACCAGCAG CTCTG

TACAAACTGAAGGATCCTGAAGTGAGACAGTTTGTTGAGAAATGCTTGGTCACTGTT TCCAG

AAGGCTTCCTGCAAGAGAGCTCTTAATGGACCCATTTCTTCAGACTGATGAGCACGG CTTAG

AATATTCCTTTTCCAGATTAGATTTCTGCAAAGATGATGTGGGGGAACTTGGCCCGT TATTAA

GAGAACCTAACATTGAAGCTTTTCAAAATGGTGCTCATAAATTACTCCAAAGCATTC ATCTTG

TGCATCCTTGTAGCAAGAATGAGATTTCTGTCCACCATGAGAACAAAAAACAACAAA AGGTT

GTACCTTTGCCCTCATACATTAGAGAGGACAGTATGTCTCACAACATGGATTTCACT GTCAA

AGGCAAGAAGAGGGAGGATGACACAATATTTTTAAGACTTCGAATTGCAGACACTGA AGGG

CGCATTCGTAATATCTATTTCCCATTTGATGTGGAAGAAGATACAGCCATGAGTGTG GCCAG

TGAAATGGTTGCGGAGCTTGACCTTGCTGATCAGGATGTTACAAAGATTGCAGAAAT GATTG

ATGAAGAAATAATGGCATTGGTACCTGATTGGAAGGCAGGGGTAGCAATAGATGATC ACCAT

TCCTTCTATGACCATTACCATTCCTCCAACAAAACAAGTGAAACTTGCTGGTGGAAT CATAAC

GATCATGCCTCCAGTATCTCTTCTCAGAGTTCCCTGTTGGAATACCTGAGGTCTCAT TACCA

CGTTGACAACAAATCAGAAATAGTGCCTTGTACTCAAGTTGAATGTGCAGCCATGCA TGGCC

GGTTTGAAGAAGTCACATTCCAGTTTAATGCAACAGATTTTTATTCATATGTAGAAG AGGAGG

CTCCTACAATTTCAAGCGGATCATCAGATGTTCTTCATCACGATTGGGTGAATGGAG AGGAT

CCAGTTTCACCTATATCTTTAATATCACATGGTTCAGGGATTAGCAATTTTGAAGAT CCCCAA

ACTTGTCTAATATCCTCAGGTACTGGTAACAAAGAGGATGTAGTTCCAAGCAAACCT GCAAA

ACCTCCAGAAACTACAGGATATGTTGGTAACTTTGAAGAAAGTTGGAGCAATGGATT GTCTG

AAGGGTTCAGTCCTGTCACTGACTCTAATTGTCTTAGCTCAGTCCCCAAACCTATGT TCCAT

CCTCAATCACCATCATCAGTCAATATTTTATCTGATGAAGATGAAGATTCCACCAGC AGAGA

GTTGCGACTTTTAGCAGTCAAACATCAGAAGGAATTAATGGAACTTCAAAGAAAACA TGAGC

ATTCCCTCTTAGGAATTGAAAATGAATTGAAAAACAGAACACCTTTGGGAACATCTT TAGATA

TGAAAAATTCCAGTCCTGGAATAAATTTTCAGGATCAGAAATTGAACGTGAATGGGC AGCGA

GAGCAGCGGGAAGATGACTCGGTTAGACATGGTACAACTGGTAGGGATAAGGAGTTT GTAG

CCATGAAACAACTTGGATCCGATGCTCGGGGAACAAGGCTTTCCAGCAGTCCCAGTC ATAG

ATTATCACCGATGGAACCAGCAGTCAGTTCTGATCTTCCAGGTCCAAGTAAACTTGC AATGC

ATTCTTCTACTCTCCCTTCTGTTAGGCCAATTAATAGAAATATAGCACCAAATCAAA GGCTAA

TGAAAATGCATTCTTTTAGTGGTGTTGACAGTCAGCGTTCTATTAATTCTCTGGCCA AAGAAG

TTAGTAGGCAGAAAAATTACCAGACAATTGGAGCATTTCGAACAGGAAATGTCGATG AAAAG

AAACATAGTCTTGAGGGGATGAGACGATTTCCATCTATATCTCAGAAATCTTCTTCA AGGAAC

TGCAAGGAAGGTAAAACTAAAATAGTCTGAGAGAACTGAAGCACACTTGTAACATAA ATTTAT

TGCCCTTAGTTTAGAATATAGATTGGATACTGCACTGAAAATTTATCAATTGTATAT ATGAGCT

TTACCTTCTGGAAGAGGTAATGGTTGGTGGTAATGCTATGCAAGGTTCTTCGGAAAT TATTC

CTTCGCCTTGGCACCTTTATGGTCTCCCAAGAATTTTGGTAGTAAGGGCAGCATTTT GAAAT

TATACAGAAACAAAGGAAAAATGTATGCATCGTCTTTCATTAGGAGAGGCTGCAACT GCCAC

GGGCTACTACATTGTTGACATGTACTATGGATTCACCAGTTCAGCTGATGGTACAAT TCAGA

TGAATTTGTGGGTTATAATCCAAATAAGTGCTTCTTGGCTGGATAGAACCCAATTCC TCACCA

GCTTTTCCAGTTAACAGAGAATTCATGTTTTTATGGCCTTTTAATTTTATGTCAAGC TTCTGGG

AAAATTTGTATCTTTGTAGTATTCAAGATTTTACGGAGAGCATAAGCTATAAAAGCA AATCGG

TCTGCAGTGTATTATCGACATCCCATTGTTTTCAGAAATCGATCAATAAGATAAGGC GGATG

CAGACTAGAAGACATGCAAGTATTGCATGTCTAAATGGCTTGATTTTCTCATCAAAA AAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

135 ATGGGATCGGGCATCATGACGGAGACTCTTACAGATTCATGGCTAGTGGGCTTGCTCTGT T

TAGTGCTGGGCTTCTTACTGCTTCAGCTCTACAAATTAGTGTGGGGGGCGAGCAGTC GAGC

CTATAAGTTGCCGCCGGGTTCTACAGGGTGGCCACTGATTGGAGAAACCATCGGCTT CTTT

CGAGGTATTAATTCCACTGCTCAACCACGCCAGTTCATCCAAGAGCGAGAGCGAAGG TATG

GGGAGATATTCAGATCAAATTTGTTTGGAAGATCTCGAATTGTTGTGTCCGTGGATC CAGAA

TTCAACAAACATGTCCTGCAACACGAAGGCAGGCAATTTCAGGCCAACTATCCCAAA CCTCT

TCGAAATCTCATTGGCAAATATGGGTTGCTTTCGGTACACGGAGATCTCCAGAGGAA GTTAC

ATGGGGCGGCTGTAAATTTGCTGAGGTTCGAGAGGTTGAGCGTGGACTTCATGGAGG ACAT

ACAGAACCTTCTGCACATCACCTTGGCCAAATGGGAAGCCAAGAGGGATATACATCT TCAAG

AAGAGTGCCATCAGCTTGTTCTGAATTTGATGGCCAAACAATTGCTGGACTTATCGC CATCC

AAGGACACTGAAGAGATTTGTGAAGCGTTTGGCCATTTCTCTGAAGCTCTCCTCGCT GTTCC

CATCAAAATCCCGGGTACCAAGTATGCAAGAGGATTTAAGGCGAGGGAATTTTTGAT AAAAA

AGATTTACGAGAGTATAGAGGATAGAAGGCAGCATCCAGAAGCTGTACATAATGATT TGTTA

ACAAAACTCTTGAAAGAAGACACGTTTTCAGAAGAAATTATAGCAGATTTTATACTG TTCCTG

CTCTTTGCTGGTCACGAGACATCGTCCAGATCCATGTCATTCGCTATCAAATTTCTC ACAGA

CTGTCCCCGAGCACTCGAGGAACTTAAGGCTGAGCACGACGCTCTGTTAATGAGGAA GGG

GAATCTAAAAAATCAAAAGCTCAATTGGGATGATTACCAGTCGTTGAAATTCACCCA ATGTGT

CATACATGAAACACTTCGTGTGGGCAACTTTGGTCCAGGAGTTTTCAGAGAAACAAA AGAGG

ACATTAAAACCAAAGGAGGCTTTGTCATTCCAAGAGGATGGACAGTGTATGTGTTTC TGACA

GGCACCCATCTGGACGAGAAGTACCATTCTTCTGCACTCAAGTTTGACCCATGGCGC TGGC

AACCGCATCTGCAAGATCAAGAGCTCTTAAAGAACCCCTCGTTTATGCCTTTTGGAG GAGGT

GCCAGGCTCTGTCCAGGAATGCATCTGGCAAAGATGGAGCTGGCCCTCTTTCTTCAT AACTT

CGTCACCAAATTCAGATGGGAGGCACTGCAGGATGATAAGATCTCCTACTTTCCTTT TCCTC

GCTTGATCAAGGGCCTCCCAATCCGACTACGTCTTCGAGAGTGACTAGACGATTAAT GTAG

GATTTAATTCATGCAGGCTGGAGTTAAAAGAAAACTATATAGAATAAAATAATTGCC ATGATG

TGGACGCTAGTTCCGATCTAAATAGCCTGGGTTTGTGTGAGTAGATTTCAGAGATAT TTATAT

TAGCTTTCCTTGTGTATCAAATCGTCGAGATTATCTTCCTCTTTGACTTTTATCGAG GAAGAC

AAATCTATTATTTTATTATTA ' ATAATTTTGAGGTTTATCAAAAAAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

136 GGGGAATGATCGTTACGGCCAACATAAAGGAGGGAGTGGCATTAGCATTCAAACGGGTAG C

AGTTGTTCTGTGAAGAAAAACATTGCAATGGCAATAATGGGGGAAACCCTTCATTCG TTGCT

AGTGGGCCTGGTCTGTTTTGCGCTGGGGATGTTACTGCTTGAGCTCTACAAATTAGT GTGG

AGGGTGGACAGTCGCAGCTATAAGTTGCCGCCCGGTTCTACAGGGTTGCCATTGATT GGAG

AAACCATCAGTTTCTTCCGAGGCATTAATTCCACTGATCAACCACGACGGTACATTC AAGAA

CGAGAGAAAAGGTATGGGGAAATATTCAGATCAAATTTGTTTGGAAGATCTCGGATT GTTGT

GTCCGTGAATCCAGAGTTCAACAAACATGTCCTGCAGCACGAAGGCAGGCAGTTTCA AGCC

AACTATCCCAAACCTCTTCGAAATCTTATCGGCAAATTTGGTTTACTTGCGGTGCAC GGAGA

TCTCCAGAAGAAGCTCCACGGGACGGCTGTAAATTTGCTGAGGTTCGAGAGGCTGAG TGTG

GATTTCATGACGGACATACAGAACCTTCTGCACACAACCTTGCCCAAATGGCAAGCA AAGAG

GGATATCCATCTTCAAGAGGAGTGCCATCAGCTTGTTCTGAATTTGATGGCAAAACA ATTGA

TGGACTTATCGCCTTCCAAGGAGACCGAGGAGATTTGTGAGGCGTTTGGCCATTTCT CCGA

AGCTCTCCTCGCCATTCCCCTCAGAATCCCGGGAACCGCGTATGCCAGAGGATTTAA GGCC

AGGGAATTTCTGATAAAAAGGATTTATGAGGGTATAGAAGACAGAAGGAAGCATCCA CAAGT

TGTCCGTAATGACTTGTTAACAAAACTTTTGAAAGAAGACTCGTTTTCAGAAGAACT TATAGC

AGATTTTATACTATTCCTGCTCTTTGCTGGTCACGAGACCTCGTCCAGATCCATGTC ATTCGC

TATCAAATTTCTCACAGATTGTCCCAAAGCATATCAGGAATTGAAGGCTGAGCACGA CGCTC

TGTTACAGAGAAAAGGGAATCGAAGAAACGGAAATCTCACTTGGGATGACTACCAGT CGAT

GAAATTCACCCAATGTATCATAAATGAAACACTTCGTCTCGGCAACTTTGCTCCAGG GGCTT

TCAGAGAAGCGAAAGAAGACGTTAAAACCAAAGGAGGCTTTGTGATTCCAAAAGGAT GGAC

GGTGTATGTGTTTCTGACGGGAACCCATCTTGACGAGAAGTACCATTCTTCTGCTCT CACGT

TTAACCCATGGCGTTGGCAGCAACTTCTTCAAGATCAAGAGCTCTCAAAGAACCCCT CGTTT

ATGCCTTTTGGGGGAGGTGCCAGGCTCTGTCCCGGAATGCATCTGGCAAAGCTTGAG CTG

GCTCTCTTCCTTCATAACTTCGTCACCAAATTCAGGTGGGAGGCACTGCAGGATGAA AAGAT

CTCCTACTTTCCTTTTCCTCGCTTGATTAAAGGCCTTCCAATCCGTCTACATCCTCA AGAGCG

ACTCGGCGATTAATCTCATTGAGATAGGATTTAATTCATGCAGCATAGATAGGATTT AATTCA

TGCAGCATGGAGTGTTAAAAAGACTAGATTTACTTGAAGGATAGAGCACTTGGCACC CTGCG

GACACAAGTCCTAGGTTTAATCGCATATGTTGGCGTGACTAGATTTGAACGCTATTA ATATG

GCTTTTCTTCTGTCTGGATGTGTAGGGATTAGTCTTCACTTCCCCTCTGATTTTCAT GGAGGA

AAACTACTGAAAGTGCTCAGTGACATTAATTACTTGTTTTTAATTTTTTTAAAGTTT TGTTTGG

TTTTGTGATCTAATAAGTTATTAAGATTACTTTTAAAATTTTGTATGGTTTTTAAGA GCTACAAT

GTTA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

137 GCTACTTCCGAGGACGCGGACGAGGAGAAAGAAAAGAGTTTGGAGGTCCCGGGATTAATT T

CTCTCCGCGCATCGAAAACGAATTTCGCCTGCTTCTGCACAGATCCAGGTTCGAATC CTCG

GGGCTTCAAAGAGGATTCGGACGGACTGAAATGCGAGCAGGAGAACAGGAGCATCAT CAC

ACATATGGGAGGGACGGTAGTAGATAGCGTCCGTAGGTGGTATCAGCGTCGCTGGAG TCAT

TCTTCAAGCGCTCACGAATCAGGAAAAGAGAAACAAACAGTTGATTCCCTCTCTTCT TCTTC

GGTCTCTCCATTACCTGTGGAAACCAAGGCGGTGGAGGGCCGTGGCTTGAAGCCTGT GCG

CGTGCAGTTGAGAAGCAAAATGACCGGGCCCGATCGCTCCAGGAAAAGCTCGCTGGA GAC

GGAGTTCTTCACCGAATATGGTGAAGCAAACCGATACCAGATACAGGAGGTTGTTGG CAAG

GGAAGCTATGGTGTAGTAAGTTCTGCGATTGATACTCATACTGACATTGTTGAGATT AAGCA

CATTATGCTTCCTCCATCTCGACGGGAATTCAAAGATATATATGTTGTATTTGAGTT GATGGA

GTCTGATCTTCACCAAGTTATTAAAGCAAATGACGATCTCACACCTGAACACTATCA GTTCTT

TCTGTATCAGCTTCTTAGAGCTCTAAAGTACATTCATACAGCAAATGTATTTCATCG TGACTT

GAAGCCAAAAAACATTTTGGCAAATGCTGACTGCAAATTGAAAATATGTGACTTTGG GCTTG

CTCGTGTCTCCTTCAATGATGCTCCATCTGCCATTTTCTGGACGGATTATGTGGCAA CCAGG

TGGTATCGAGCCCCTGAGCTTTGCGGTTCTTTCTTTACTAAGTACACTCCTGCCATT GATATC

TGGAGCATAGGATGCATATTTGCTGAAATGCTTACAGGAAAGGCATTGTTTCCTGGG AAGAA

TGTTGTACATCAACTGGATATCATGACTGATTTGCTTGGCACTCCGTCAACAGAAAC ACTTTC

TAGGATCCGCAATGAGAAGGCCAGAAGATACTTAAGTAACATGCGGAAAAAACAGCC AACA

CCCTTCTCACAGAAGTTCCCAAATGTAGATCCACTTGCTCTTCGTCTGCTTGAGCGT ATGCT

TGCATTTGATCCAAAAGACCGACCTACAGCAGAGGAAGCATTAGCTGATCCATATTT CAATG

GTTTGGCAAAAGTTGAGCGTGAACCTTCAACGCAGCCTATTTCAAAGCTGGAGTTTG AGTTT

GAAAGGAGAAGATTAACAAAGGATGATGTGAGAGAGCTTATATATCGAGAGATTTTA GAGTA

TCATCCTCAAATGCTACAGGAGTATCTATGTGGTGGCAACAATGCCACCTTTATGTA TCCAA

GTGCTGTAGATATGTTCAAGAGACAATTTGCTCATCTAGAGGAACACTATAGTAAAG GTGAA

AACAGCACACCCCTTGGGAGGCAGCATGCCTCTTTACCAAGAGAGCGTGTCATTGAA TTCA

GAGAGAATCCTACAAAGCACAGCAAGGATTCTGAAAAACAACAAGAAAGAATCACTG CGTCT

GTAACTAAGGCTACCCTTCAAAGTCCACCAAGAAATCAGGGAATTGTGATTGATTCT GCAGT

TTCACTATCTAATGGTCCAAGTAGAGCAGTTCCAGATCCACGAAACCTAGTGAAGAG TGCTA

GCATCAATGCTTCCAAGTGCACAGTTGTTGTCAATTCCTGTCAAAGAAGAAACTCCA CAATG

AAACCTGGGGATGAGAAAAAGGAGGACTTGAGCAGTGAATCGAGTGCTGTCACATAC AATA

CAGATTCAATGGTTGCTGGTTTGACAAGTAAGATTGCTGCAATGTCCAGTGGAGTGG CACAT

TCATGAATACTTCATTGTGTTCAAATCATTCAGGGCAGTGGTTACTAACCTCTAACT GATTTG

GTTACAACATATTCTGAAGTGTCCTAAGCCAAGCATAGACTGAATGGCTGCTGGCCT GGTAA

AGAAGGTTACAGCGATACCTAGTGGTTTGCCTTATTTTCATGAATATGTTAATGGTC ATCTAA

TTTTTATATTGTATCGATTGTGACCTGTTTAAAAAATATATTTTACTTTAACTGGCT TCTTTTGT

GTAATCAATAATTAATCTGTCTCAGTCAAAAAAAAAA

138 GTGGCCTGCCTTCCCAAATTGTACAATCATTTTAAACCCAACATCCTACAAATAGGATCA TTT

GGAGCGTCATTTCACTCGGTTTTTCTCTTTCAGTTTGAAGCGGTGGAGAAATGGTCT GTAGG

CAAACTAACCATTTCTGAAGAGCAGGCCTTAGAATTGTAGGGTAATTTGCAGTGGAC AAGAT

GGCTTACAGAGCAGATGATGACTATGATTATCTCTTCAAGGTGGTACTGATTGGGGA CTCTG

GTGTGGGCAAGTCCAATCTGCTGTCGAGATTTACTAGGAATGAGTTCAGTTTGGAGT CCAAA

TCCACCATCGGAGTGGAGTTCGCGACTCGGAGTATAACAGTCGATGATAAGGTCATA AAAG

CTCAGATTTGGGACACAGCTGGTCAAGAAAGATACCGGGCCATAACAAGTGCATATT ATCGA

GGAGCAGTTGGTGCACTGTTAGTTTATGATGTAACTAGACATGTAACCTTTGAGAAC GTGGA

GAGATGGCTTAAGGAGCTTAGAGACCACACTGATGCCAATATTGTCATAATGCTTGT TGGTA

ACAAGGCTGATTTGCGCCATCTTAGAGCTGTTTCTATAGAGGATGGAAAAGCATTTG CAGAA

CGAGAAAATACATATTTTATGGAAACATCAGCTTTGGAATCAACAAATGTTGAGAAT GCATTC

ACAGAAGTACTTAGCCAGATTTACCGGATTGTGAGTAAGAAAGCTCTTGATGTTGGG GAAGA

CCCAGCAGCGGTGCCCAGTAAAGGGCAGACGATACATGTTGGCAATAAGGATGATGT GACA

GCAATGAAGAAAGTTGGGTGTTGTTCTTTATAAGCCCAAAGTGCAGTGCTCTAAAGT GTTGT

CGTCTGAAGCTTTTGCTTCTAAAGCGATTCTTTTTGAGGAATTGATTTAAATGTCAA AAGAAG

GATTGATGGTTGCATGTCAGTTTTAAGAGACAAGCACCCTGCTATTGCTCTGTATGA TTTATT

AGTGAACCTTTGCTGCTCTTGGATGCCTCCAAAGCGCATTGTTGTCATATAGCTTTT GTTGCT

ACTATACGTTTTAGCAAATATTTCAATGATTTGTATTGTGGTTATTTTGGACAGATC ATGTCAA

AAAAAAAAAAAAAAAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

139 AAGTCTTAGTTGACTCCACCCACCCCTGGGCCAGCTTCGAATCTTTCATATGTGATAAAT CA

GGCGAGACTTACCATAAGTAAGCCTAAACGCATTTATATCAAAGTTTCACCTGAGAG TTCCC

CAGTGGACACTTACTCAAAATATGAGTTTATCAAAGTTCTACCTGTGGATTCTCCAA TTCACC

CTTAATCAACCCATCCCAAAATAATTGGGAGTTTCTGAGTATCTAGGGTGAGTGGGT GACTC

CATTCATCTCTCTGACAGATGACAGATGAGGTTAAGATGCTGTTGTTGGTGCTGCCG CTGCC

ATTAGCATTGGGTTTCGTTGTGCTAGGCTGGAATCTGGATGTGGCCTTATTTTAATG AAGCC

CCCGTATCCCGATGGTCTTCACTCTCTCGGCCCCGCTGGGCATCCTTCATAAATATC TATGT

TCGCTGTAACAAATTGCTCAGGCCTGTGACCAAGGGGAAATGGAGCCCACGCCCAGC GCT

CGTAATTAGCTCGAACTAAGAACCAAAGTGTGGACCATCTGACCATCCATCCATTCA TTGCC

TCTCCGGCTCTGGAAGTTTGAGGGGGGCGAGATTTGTCCACTAGACCAACGTGGATT CGGG

ATAGGCTGTTGTTTTCGAGAGATCTGAAACAGCGGGGGCTGCAGGAATGGAACTGGA GACC

TCCTACTGAAGGCCAACAGTGCGAAGGGGTTCGGAATGATGAAGAAGAGAGGGGATT CTTC

GTCTTCATTCCCAGACGAGGTGCTGGAGCACGTGTTGTTGTTCGTGGTTTCGATCAA GGAC

AGGAGCGCGGTTTCGCTGGTATGCAAGGCCTGGTACAGAGCCGAGGCCTGGAGCCGC CG

GAAGGTCTTCATTGGAAACTGTTATTCCGTCTCGCCGGAGATCTTGGTGAGGCGCTT CCCA

AAGATAACAGGCATAACTCTCAAAGGAAAGCCGCGCTTCTCAGATTTCAACCTCGTT CCTCC

CCACTGGGGGGCGGATATTCACCCCTGGCTCCTGGTCATACGCGGGGCCTATCCATG GCT

CCGGGAGCTGAGGCTTAAGCGCATGATCGTCACGGATGAAAGCCTTGAGCTCATAGC GCG

TTCCTTCTCCGATTTCCGCGCTCTCTCGCTCACCACTTGCGAAGGTTTCAGCACCGA CGGC

CTCGCAGTCATCGCAACTCATTGCAGGAACCTGCAAGAGTTGGACCTGCAGGAGAGT GAGG

TAGATGATCGAGGCGGTTACTGGCTGAGCTGTTTTCCAGAGAGCTGTGTTTCACTAG TGTCA

CTGAATTTTGCTTGCTTGCAAAGTGAAGTGAATTTTGATGCCCTTCAGAGGCTTGTG GCTAG

ATGTATTTCTTTGAGGAGTTTGAAACTAAATAAAACTCTTTCTTTAGAACAATTGAA GCGGCTT

CTTGTAATAGCTCCTCAGCTGATGGAGCTGGGTACAGGTTCATTTTTTCAAGAGCTC AGTGG

TCCGCAATTTACTACAGATCTGGAAAATGCTTTTAAGAACTGTAACAAACTTAGAAC TTTGTC

AGGGATGTGGGAAGTAGCACCTCTGTATCTTCCTGCCTTGTATTCTGTGTGCTCAAA CTTGA

CATTTTTGAATTTAAGCTATGCGGCCAATATCCGAAGTATGGAGCTGGGCCGTCTTG TTTCT

CATTGTCCTCAACTCCGGCGGCTTTGGGTTCTTGATACTGTTGGAGACAAGGGTCTG GAAA

CCGTATCATCAAACTGTAAGAACTTGAGAGAATTGCGGGTTTTTCCATTGGATCCAT TTGGC

CAGGATCGAGTTGGTGTCACAGAAAAAGGCATCCTTAAAATATCTCAAGGATGCCCT AATCT

TAGTTATGTTTTGTATTTCTGTAGGCAAATGACAAATGCAGCAATTATTGAAGTGGC TCAAAA

TTGCCCCAGGTTAACACATTTTCGCCTTTGTATAATGAATCCCTGCCAGCCAGATCA TTTGAC

AGATGAACCTATGGACGAGGCTTTTGGAGCAATTGTAAAGATATGTAAGGGATTACA ACGAT

TGGCAATATCAGGTTTGCTTACTGATAAGGCTTTTGAGTACATTGGTCTTTATGCAA AGAATC

TAGAAACCTTGTCTGTGGCCTTTGCTGGAAGTAGTGATTTGGGCATGGAATGTGTAT TGCGG

GGATGTCCAAAGCTTCGGAAGCTTGAGATAAGGGATAGTCCATTTGGCAATGCTGCC CTCC

TATCAGGTCTTGAACAATATGAATCCATGCGTTCATTATGGATGTCTTCTTGCAAGG TTACGA

TGAGTGGTTGTAGATACCTTGCTCAGAACAAGCCCAGGCTTAATGTGGAAATAATAA AGGAA

AACGATGAAGATGACAATGATGCAGACAAATTATATGTCTATCGGACAATTGCTGGG CCAAG

AAGGGATGCTCCAAATTTTGTGCTCACCTTATGATCAGATTCTTCTTTTCATCGTTA TGGACA

GTCTGGTTAGCTGCCTGGATTATCATGAAATGATTACAGGGAAGAATCATCTTGTAT ATATCT

GTGACTTGCTCAACATGTAGGATGGGATACCTGCTGAATTGAGACACACCATTGTAA GGCAA

GGCATCTGTCATTAGATGTGGATGACTGTTGGTTTTTTCTCATTGGTGTGTACTATC CATTAA

AGGTGGCACCACCAATTCGTCAGATTTGAGTCCTTCGTTTATCGGACTCACAAGTTT CATTT

CATAATAGGTCTAATCTTGGTTAACTTGTGAGTCCCTCGTGCCGAATTCGGCACGAG GACG

GACTGTGCTGCTGGAAAAACTCGTGTTTTCGTAAATGGTAGGGAGCTCCATCAAAAA GACTT

GGATTTGCTTGCTGGCAGAGGTCTACCAACCACAAAAGACAAGTATTACCACGTTGA GATCA

GCGGAAGAGTTGTGGATAAGGATACTAATAAAGAGCTGAAGAGTCTTGGCAAGCTTG CACC

AACGTAGGTCACCAGTTAATATGCATTCTTCTTTCAGAAATTCAAGGAAGTAGAGCA AATTTT

ATTTTCCAGTATGTCAAATTTGGCTTTGGGCTACCAGGTTTTTGTAATTGATGTTTG AAAAGT

TATACATGTTTTTCAATGCATTTCCGGGCAATAACACTTCTCGTGCCGAATCGGCA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

140 CATAACTACAAACCGTAACGCATGCCTGGAGCAGTGTCCATAACGTCAGTACGGTCGTGA G

CAGCAGGAAACTTTTTCCGTGCTCCTTCTCACATCTTCTTGTTTGCTTCGGGATTCG ATATCC

TGACCACTTTACTCATCAGCCCGCTGAATTCTTCTCTAGACTTGCTCTTTTCCTGTC ATTGAG

GGCCAACACAGCCAACGGCTTCGTTCAAAATCGGGCCACAAGAATGGTCGATCACTC GCTC

ATTTACAGTTTTGTTTCGAGAGGGACGGTCATATTGGCCGAGTACACGGAATTTACT GGGAA

TTTTCCCACCATAGCTTTCCAGTGCCTCCAGAAGCTCCCGGCCACCAGCAATAAGTT CACAT

TTGACTGTCAACACCACACCTTTAATTATCTCGTTGAAGATGGATTTACATATTGTG TCGTGG

CAGATGAATCAGCTGGAAGACAAGTACCGATGGCCTTCCTGGAGCGCATTAAAGATG AGTT

TAAGAAGACGTATAGTGATGGAAGAGCTGAAGTAGCTATTGCCAACGGTCTTCACCA GGAAT

TTGGGCCAAAATTGAAAGAACACATGGACTATTGTGCACAGCATCCAGAACAGATCA ATAAG

TTAGCCAAAACCAAGGCTCAGGTTGCAGAGGTCAAAGGCGTTATGATGGACAATATT GAAAA

GATCCTTGATCGTGGTGAGAAGATAGAACTGATGGTTGATAAAACAGAGCAACTTCA ATTCC

AGGCTCAGGATTTTCAGAATCAGGGTGCTAAGATACGCAGGAAAATGTGGTTCCGGA ATAC

AAAAGTCAAGCTAATTTGTCTTAGTTTCTTGCTTTTTGTAGTTCTCATGATATGGAT CTCTCTA

TGCCGTGGATTCAAATGCCATGTCTGAACTAATAAGTTTGTAGCTATCAACATGACT AAGCTT

TAGTGAAGGGCTATACAATGCATCTTTATTCTTCTATTGTTGTTCTCTCTACATGTA AATGGT

GTTTGCTGGAAAGGTAATTCTTTTTCCTGTTTCTTCAGAGTAAAAAAAAAA

141 CTGCAATGTCCGGTCTCATCCTTTTTCAATCAATTCCATTGCCATTTCCCTCCCAAACCC AAA

GCATAGGGTTTCCTTCATCTCGGCGGATCTCGAGTTCAATCCCTTCTGCCCATGAAT TTTTG

CCTTTTTCGATCCCATAGTTGAAGCTCGACGCAGGACGAACAGATCGGGGCAATTAA CATAC

TTATTCATTCGGACTTTCATTCGCTTCAAACATCGGTGGTTCGAACGCCGGGGCGTCTGG AT '

ATAGCAGCAAAAAGATTACGCAAAGGCAGCGGCTCTCATGGCGATACTGTATGCCCT GGTA

GCCCGTGGTTCCACAGTTTTAGCGGAATTTGACGCGGCTCACGGCAATGCGAAAACC ATAG

CGCGTCAAATTCTGGAGAAAATTCCAGGTACCGGGGACAGCCACGTCTCTTATTCGC AGGA

TCGCTATATTTTTCATGTCAAGAGGACTGATGGATTGACAGTTCTATGTATGGCTGA CGATAC

AGCCGGAAGGAGGATTCCTTTTGCATTTCTAGAGGATATTCATGGAAAATTTGTGAA GACTT

ATGGTCGAGCTGTTCATACGGCACTTGCTTTTACTATGAATGATGAATTCTCAAGAG TCCTG

AGTCAGCAGATGGAATATTATTCAAGTGATCCAAATGCAGACAAGATTAATCGTATA CGAGG

AGAAATGAGCCAGGTTCGCAATGTAATGGTGGAGAATATTGACAAAGTACTCGAGAG AGGT

GACAGATTAGAGTTGCTGGTAGATAAGACTGAAACGATACAAGGGAATACTTTCAAA TTTAA

GAAGCAAGCTCGTCGTTTCAAAAATACAATGTGGTGGAGAAACATCAAACTCACGGT CGCA

GTGATAGTCGTGCTTTTGATCGTCATCTATGTCATCCTCGCTATAGTTTGCAAAGGT GTTACA

CTACCGTCCTGCAGAAAGTGAATCGAACCGTTTGAATTTGTGGTCAGTGTCGTGTGT ATTTT

TAGAAGGCACAAAGGTTTTTATTTTGGGAGGCTATTGGTTAATACATATAAAGGGTG GTAAA

GCGCTGTTCATATTTTTCCTAGAAGTATTGGTCATTTTCTGTGTAAATTAGATTCAT TGCCGT

CAAAGAAATGAAGATTATTTGGAACATGAGGAAACATATTTTTTTCCAGGCTTTGAG CACAAG

CATTACTCTTATGGTAATGACATGGCATGGAAGATTAACAAACATGATTTTTATTAT CTATATT

TATTCTGTTATCAGTTCAAGCACTCGGAATATTTGTTCATGAGCCTTTTTCATTTAG TTTGGAA

GTGATCATTTGTAACAGTTTTTTGACACTTTTGAATTGTTTTGTAAGATGTGCCCAT CTACTTT

ATCGGAAGAAGGGAGACACTCTTACTCATCTTTGGATATTTTCAGTAATTTTTAATA ATAGAT

CAGAGAGTTCAAGATGGATTAAAAAAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

142 GGAAGAACTTTGCGTTTCCCTGCATTTCTACTTGTACCCTTATTCATTCATTCAAGAAAA GAA

AAGGGCAATGGCTGTAGTTGCTTCCAATTCTCTACAACTGCAGCGTGAAGAGGAGGC AGAG

ACGATGATATCAGATCAACAGCAAGAAGCTGGGGCGGAGATAATGGCATCAGAAGAA GAGT

CGATTATGGAACCAGAAAACCCGTCATTGTCTCATCCCAATATTGTGTCCAGCTGCG GGATG

AGGTTCCAAAAGTACCAGAGTGTTTGGATTGACGCCAACTTAGTCCCCGCAGTGAAT TTCAT

CCAAAACGAATTTCAACCACGCCCCGACGACATTTTTTTCGCTTCCCTTCCAAAGAC TGGAA

CCACATGGGGTAAGGCGTTGCTGTATACCATCTTGGAATTTACTTCCACAGGCAATA ACCCT

CCAGCAAGCCCGAATGGTAATTCTGCTGCGGATGAGAAAAGATTTGGTGTGGATGAG AAAA

ATCCGCATGCTTTGGTCCCAACCATGGAAACTTATCTCTTCAATTCAAGTGACAGCG AACAG

TATGATATTTCCTGCTTCTCTGATTTTCCGTCTCCGCGTGTGCTCCACACACATTTG CCAATC

CATACGCTGCCTCTTCTTGTGAGATCTTCTCCGACTTGCAAGATAGTTTACATTGCC CGCAA

CCCCAGAGATTCCTTCGTTTCCCTTTGGCAATTCTACGCCAGACTTCGCGGAGCGGG GTCT

CATTATTTGGACGGAGATCTCGGCAAGGAAACGGTGTTTGATGCATTTTGCTCTGGC TTCTA

CTATGGCGGCCCCTTTGCCGAGAACGTTCTGAGTTACTGGCATGAAAGCAGGCGCAA TCCG

AATCAGGTGATGTTTGTGACGTACGAGGACCTGCAGGCCGATTGCGTGGGATGGGTT AAAA

GAATGGCTCTTTTCTTGGGTTGCTCTTCTCCTCTTCTGGAAGACAACGCCCAGATAA TTGCA

GAAAAGTGCAGTTTCGATACCCTCTGCAATCTGCAGGTGAACAGAAAAGGAAAAGTG GGGA

CGCTTAAATACGGAATGAAAAACGCCTTCTTCTTCCGCGAGGGCAAAGTGGGCGAGT GGAA

GAAGCATTTTACGCCACAGATGGAGGAGCGTATTTATTTAGAGATCGAGCAGAAATT GAGCG

ATCAAGGCCTTCGTTTCACTAATAGCTTGTAGAAAGCCATTTCGTTTGTGTTGAATT TATATTA

GCTAGATAGCTATCAGGTCCTCGGATTCTGAAATCTTCCTGAACTCTACAGTTAAGA TAAAG

AAGTCACATCCATTTCCATCTACTTATTACTTTTATTGACCATCAGTTGCAGTGAAG TTCCTTA

GTGCAATAAAAAAAAAA

143 TTGGGTTCGGGGTCCTGTCCTGGACTGGGAATTTTTGTTTCACTCGTTCTGCCCCGTCTG GA

TTGGGCTGCACTGAAATACATTGAACATTGGAGTTGTCGAGCGCGAGATATGGGTCA GCAG

TCCCTCATTTACAGCTTTGTTGCAAGGGGCACGGTGGTCTTGGCCGAGTACACCCAA TTCA

CGGGCAATTTCACAACAATTGCCAATCAATGCCTTCAGAAGATTCCTGCCAGCAATA ATAAG

TTCACCTACAATTGCGATCGTCACACATTCAATTATCTCGTCGAAGATGGTTACACA TACTGT

GTTGTTGCAGATGAATCAGTTGGAAGACAACTACCAATTGCCTTTCTGGAGCGCATT AAGGA

TGACTTCAAGAAACGATATGGTGGTGGAAAAGCTGACACAGCTGTTGCTCACAGCCT CAAC

AAAGACTTTGGACCAAAATTGAAAGATCATATGCAGTATTGTGTTGATCACCCAGAA GAGATT

AACAAACTTGCAAAAGTGAAGGCTCAGGTTTCTGAAGTTAAAGGCGTAATGATGGAG AATAT

TGAGAAGGTCCTTGATCGGGGTGAAAAGATAGAACTTTTGGTTGACAAAACAGAGAA CCTTC

GATTTCAGGCTCAAGACTTCCAGAAGCAGGGAACACAACTTCGCCGAAAAATGTGGT TTCA

GAACATGAAAGTCAAACTGGTTGTTCTTGGAATTGTCTTTGTGTTGATTCTTATAAT CTGGCT

CTCAATTTGCCATGGATTTAAGTGCCATTAATCTTGATTACTTGGCAGTCCTTTCTA GATACA

ATCCTTTCGAGGCATTTATATTCATTTTTTGGCAGCTTGGCTTATAATAGATGCAGG CTCTCT

TTGAAAAGAGTATCTTTTGTGTTGTGTCTGAGTAATGTATTTCATTCACTTGGATAC TCTCATC

ATTAGATACTGATTATCTATGTTTTTCTCTGACGAGGGACAATGCCTCGACTCTTCA TAGTTT

AGGTTATTGGCACTACCCATCAGCTGTGATGTCAATCTCTTTTATAAATATGAATCC CTGCTT

TTGGTTTTCAAAAAAAAAAAAAAAAAAAAAAAAAAAAA

W 2

IABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

144 GCATATGCGAATAGCACATCAAATCGGGTTGCGACTGCCTGCCACGTTCGATATCTCAGG C

TCTTCGATGAAGCTGAGTGCCAGAATCAAATTTAATAATCAATGAATAATAACAAGG GAAATT

ACTGTAGATTGCGAGAQGTTACAGTTTACTTAGGATGACCCCAATGATTTCTCATCT TTGCTT

CAATTCAGTGTCGCAGAGGGTGCTCTTCCATGTCTGAAGAAAAATGTGAATGATGCT CTGCA

ATACAAAATTTTCTCGCATTGTGGACGCGTGGTAAGTGCAAGAAACGAGTGAAGGGG AGAA

GGGGGGGTTTTGCCTGTAAGAAAGGATCAGAGAGAGCAAGCATCCAGTAGCCATGGA AAAC

ATGAGGAAGAAGTTGGGGCCACTGTTCAACTCCGGGCAGAGTTTCCGTCCTGACATC TCTG

TTGATTCCTGTACTTCATATAAGGTAACAGCGGGTGGAACTTTACACTTGCTGAGTA ATTCGT

GTGGAGAATATAATATTAATGAACTTGGCTTACAAAAGCGCACTTCAGCAGGTATTG ATGAAT

ATGATACGAATGAGAAAACATATCAGTGTGCTTCGCATGAGATGTGCATATTTGGTG TCATT

GGACGTGGTGCAAGCAGTGTTGTCCAAAAGGCTATTCATATACCAACTCATCGGATT TTAGC

ACTGAAGAAAATAAATACTTTTGAGAAGGAAAAACGGCACCAGCTATTAAATGAGAT TCGAA

CACTATGTGAGGCACCACATGTGAAAGGCTTAGTGGAGTTTCATGGGGCTTTTTACA CTCCT

GCATCTGGACAAATCAGCATTGCTTTAGAATACATGGATGGAGGCTCACTTAGAGAT CTTGT

GCAGTCAAAGAAGCGTATTCCTGAGCCAATTCTTTCTGTTATTACACATGAAATTTT ACATGG

ATTAATTTTTTTACATCACGTGAGGCATCTGGTGCATAGGGACATAAAACCTGCTAA TCTGCT

TATAAACCTTAATGGAGAGCCAAAAATTACAGATTTTGGCATTAGTGTTGGTTTGGA GAACAC

CGTTGCAATGTGTGGCACATTTGTTGGGACCGTCACATACATGTCACCAGAGAGAAT TGGTA

ATGAATATTATTCATTCCCAGCAGATATCTGGAGCCTAGGACTTTCCATTTTTGAAT GTGGTA

CAGGAGAGTTCCCATACAATGCAAGCAAGGGCCCTGTGAATCTCATGCTACAGGTCA TAGA

TGATCCATCTCCCTCACCTTCACGAGATTGCTTTTCAGAGGAGTTTTGCTCATTTGT TGATGT

CTGTCTACAGAAGGATCCAACTGCAAGGCCTACAGCAGAACAGCTCTTATCACATCC CTTTA

TTAAAAAATATGAAAATGCAGGAGTTGATCTGTCAGCATATGTACAAAGTATTTTTG ATCCTA

TAGACCGTCTAAAGGATTTAGCTGATATGCTTACTGTACATTATTACATGCTTTTTG ATGGCA

CCGATGATCAGTGGCATCACATGAAAACTATGTACCGTGAGAATTCTGCTTTCAGCT ATGCA

AACCAGGTTGCAGCTGGAGCAAATGATATCTTTAATACTCTATCACGAATACATAGC ATGTTG

GTTGGTGATAGCCCTGATGAAAGGCTTGTTCATGTAGTTGAAAATCTTCAATGCTGT GTATAT

GGGCAACATGGTGTTGTGATCCGTGTATCTGGATCATTTGTTCTTGGAGGCCAGTTT ATACC

AACTGGGGGTGGGGTGCAAGTTGAGGGGGTTTCACAAGGACCTTTGTTGGACATAGC ATCA

CAAAGAATGGGGACCTTTAATGAGCAATTCATCATGGAACCAGGAGAGCAGATTGGA TGTTA

TTATATATATAAGCAGGAGCTGTGCATCCAACAGTGAAAAAAATGCATACAACCAAA TTGTCT

TTTTGCTTCCGTACAGTCTATATTCTCTGGTACAGGAGTGCTGTAAAAAAGCAGCCC AAGAA

CAGGAAGCTTGTGAAGGGAGTTTCCATCATAGCAGTTGTAGCAGGGGTTGGAAGATT CCTT

GATGTTATAACTTGTATGCACCATGTATCACCATCAAAGAAAACCCACATCTGCCTT CAGATT

GATTGACTGGGAAGTAAAACAGGCATGGGAGACAACTTACTGGAAGCAGATGAACAG CTAA

TATTTCAGTGAAGATTTGCTCAAGAGATTATTAGAGACTGATGAACTAATAACTCTA AACAGA

TCAATACATCACTGAAGTTTGTGTTGCAACCCTCATGAAGATGGAGAATAGCCTATG CATATT

TTGATGCATCTATAGTTTACTAAATTTGGAATCTGTAGCTGTTGTGATGGTGTTCTG ATTAGA

GTAGCTTTATGCAGCCTTGAGATAATTTTAAATGGCTGAGAGTTTTGTTGATAAAGA GGAAGA

GTAATACTGTTGCCTCAATGACTGAATAAGGTAAAGAATTGTGATAGTTGGACAAAA AGGTTT

GGTAGTTTAAAGGCAAACACTTGCAGTTGTCATGGTATGGGCCTTCTTAAAAAGGTT GTTAT

CATGTCAGATGCCATTACTCGATGCTTTCTAATGTTTGGTTAGTATAAAGATCTAAA AAAAAA

A

IABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

145 AAACGCGGCCGATTTTACCGGACGGGCGAMTCACCATGATCGATAGACACAGTTCGAGGT

GAATGGAAGCTTCGCCGTTGATCCAAGCCACCTCCGTGGAGTGACGTGTATTGTCTT GACT

TATAGCTGTACAAAAGAAAGAAGTATCGAGGAAAATCCGATAAATATAAAATTCAGG TTCAAA

TTCTCAGGAAATAGCTTAAATTTCGCTTTCGATCGCTATCAGAGCCTTGAAAGTTCA GAAAAG

ATTGAAAACGCGGTCTTTTGGCAAATTGAAGAAACGGAAATACTTCGGAAGGATTCG GTAAT

CCCGCACGTTTGACATTCTTAGGTCAAGGCTTAAAGTTTTGTGGCTATGCATGGGGA TAACT

TGCTTTCAGGTGATTGAAAATTGAAAATTTACTAAACTTTGATGGCTTTGTTTTGAG GCTCGG

CGAATTGATCTTTACGGTGCTTTATGTGAGAAATTCTGTGGAAAAATCTGGTCTTCA GAGATC

TTTAATGGTTTTTCCTGAAGAAATGATCATGCTCCAAAAGGATTCCACAGTTCTGCA TTTCTT

AGCTGAAGCCTAACAGCTTTCCGGGTATGCATCGGAAATATCTTGGTTTCATTTGCT GAAAA

TTTTCAAAATTTACTGAAATTCGAAGGATTTGTTTTGAGGCTCAGTGAGTTGATCTT AACGGT

GTTCTTTGTGAGAAATTCTGTGGGACAAATTGGACTCGAGAGACATTTAATGGTTTT TGCTAC

AGAATTGTGGAATTATCTCGTGTGACCTTAAAGGCTCTTGCGGTCTTCGTTCTTGCA CGAAT

TTTGGCTAAAACTGCTGAAAGAAGTCCAGTTTCAACGCATTTAAGAAAACTACTCAA ACATCG

GTGAATTCAGTGGAGTCTTCCAATCGAGGAGGCTGCAACAAGAAATTGTTCCTGCTG GGAC

TATTTATATCGGCAAATTAACCGAAGTTGTGAGGATATGGAATTGGTTCGGAAATAG TTCATT

AGCGGGACAATTTGACAGGAATCATCAAGCTAAGCTTTTGCTTGGAACGCTTATAAA ATTTTC

TGTTAAAGATCGGTCAATTTTGAACTCCGGCAGATAAAGGTCTGGTTTGTGGTGTGG AGCG

GAGGCGGCTGCTGTTGCAGTTAAATCTAACGATCCGGTAATGGCCCAGACAGCCCAA CCAG

CTTTAGATCCCAATATTCCCGGCGTTCTTACTCATGGAGGCCGGTTTGTGCAGTATA ATATTT

ATGGCAACATGTTTGAAGTTACCGCAAAATATGTCCCTCCCCTATTTCCTATTGGAC GAGGA

GCATACGGTGTGGTCTGCTCAGCACTGAATTCAGAAACCAATGAGCAAGTTGCATTA AAAAA

AATATCCAATGCCTTTGACAATTTAATAGATGCAAGGCGGACCCTACGAGAAATAAA ACTGC

TTCGACACATGCAGCATGAAAATGTTATTTCCATCAAGGACATAATGCTTCCCCCTC AACGA

GAAGCTTTTGATGACGTGTACATTGCATTGGAGTTAATGGATACTGATCTCCATCAA ATTATC

CGTTCAAATCAGGCTTTAAGCGAGCAACATTGCCAGTACTTTTTGTATCAGATATTG CGAGG

ATTAAAATATATACATTCTGCAAATGTCCTGCATAGGGACTTGAAGCCCAGCAATCT TCTTCT

GAGTGCAAATTGTGATCTCAAAATAGCTGATTTTGGACTAGCCCGAACTACATCTGA AACTG

ACTTCATGACAGAGTATGTGGTTACACGATGGTATAGAGCCCCAGAATTGTTATTGA ATTCA

CCAGATTATACTGCAGCTATTGATGTGTGGTCAGTAGGTTGCATTTTCATGGAATTG ATGAAT

AGGAAACCCTTATTTCCCGGCAAAGATCATGTGCATCAGCTCCGTTTAATAACAGAG TTAAC

TGGTACCCCAACTGATGCTGATCTAGGTTTTATTCGGAGCGAAAATGCAAAACGACT TGTTC

AGCTGTTGCCTCAACTTCCAAGACAATCATTAGCTGAAAAGTTTCCACATGTACATC CTTCAG

CTATAGACATTTGTGAAAGAATGTTAACATTTGATCCAAACCAGAGAATTACAGTGG AGGAA

GCATTAAATCATCCTTACCTGGGTAGTCTGCATGATGAAACTGATGAGCCTACCTGT CCAGT

TCCATTCAACTTTGACTTTGAGCAGTATGCATTGACAGAAGAACAGATGAGAGAGCT GATAT

ACATGGAGGCTCTTGCATTCAATCCAACTTAGAAGACTGAGTGGTGGTCTTTTTTCT TGTTTC

AGATTGCACAACTGGTTGTTTTGTTTGATATTAAGATAAATGTTTGATTTAMTTTTG AGCTGT

TATTCTCCAGTTGAGMGCATGTTACCTTGCACAMGGAAMTCAATATATAMACATAAA TT

TGATATTTGMCAGCMTATGCCAGMCCTACTAMCTGGATGCTAMTGAGCCAGACGTTC

CAMTMTAGACAGTTMCTAACACCATTATTTAGTAAAMMAM

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

146 GAAAGATGAGTGATCATCGGCCTGTGTCAAGGTGCCTAGAGAGGTAATGGGAATTGGAAA T

ATTTATAATAGTAATGGTAATTGGAAATTGACAGAGAGGACGCGTTAGGCTTTTAGG CAGCC

ATGAAGAGATGTGAGGGATGCTTCGAGGTCGGCAGGTTGGAGGCCCTAGGCGACGAC ATT

CTGCTGCAGGTTCTTGACAATATTAACGAAACTCGAGACAGGAATTCATGGTCTCTT GTCTG

CAAACAGTTCTATCGACTCGAATCGGCCTACAAGAGGAAAATCCGGTTGCTCAGAGG CGAA

ATGCTGCCAAGAATTCTCAAGAGATACCGAGCTGTAGAGCACCTGGACTTGTCCCTC TGCC

CTCAGATCAGCGATCAGTGCCTGGGGTTCGTGGCCGCAGCGGCTGGGTCTAGTCTGC GCT

CCATAGATCTTTCGAGGCTCGTCCGGTTTAGTCATCTGGGGCTCTCCGTTCTGGCTA AGGG

CTGCGAGAATCTGGTGGAGATTGATGTTTCTTACTGCGCGAGATTTGGGGATATGGA GGCT

GCTGCCGTTTCCAGTGCCAAGAATCTGCAGACCCTGAAATTAGTGAGGTGCCAGATG GTTT

CTGACTTGGGTTTGAGCTTAATAGCCGTGGGGTGCAGGAAGCTCCAGAATTTGAATC TCAAA

TGGTGTGTGGGAGTTAGTGATTTGGGTGTTGAGCTCGTGGCTATAAAGTGCAAAGAA TTGA

GGTCCCTGGATGTTTCTTACTTACAGATAACAAACAAATGTATTGCATCCATCACAC AACTTT

TTTACCTAGAAACTTTTGTATCAGTTGGTTGTGTCTGTATAGATGACGAAGGCCTTG CTTTGC

TCAAGAATGGTTGCAAATCATTGCAGAGGCTTGATGTTTCGAAATGTCAGAGTATGA GTTCG

ACTGGTATAATTTCCCTTGCAAACGGATGTATAGCCTTGCAGCAACTAAACTTAGCC TATTGC

ATCCCTGTCACAAATGCTCTTCTTGCGAGCTTCGACAAATATGACAGCCTGCAATCC ATACG

ATTTGATGGCTGTGAAATTTCTAGCTCAGGTTTGAAGTCTATTGGGAAAAGCTGCAA GTCTC

TGATGGAATTGAGCTTAAGCAAGTGTACTGGGGTGACAGATGAAGGAATCTCTGCAC TAGT

GGGAGGCTGTACAGGGTTGAAAATTCTAGATATCACCTGTTGCCGTGATCTCACTGA TGTTG

CTATCACAGCTGTTGCAACATCCTGTGGAAATCTTTCATGTCTTAAGATGGAATCCT GTGCC

CTGGTCACTGAGAGAAGCTTATATATGCTGGGAGATAGCTGCCCCTTTCTAGAAGTA CTAGA

TCTCACCGATTGTAGTGTAAGCAATACAGGACTGAAATCCATTTCCAGGTGCACTGG ATTGA

CTACCTTGAAACTAGGCCTATGCGAAAATATATCCAATGAGGGTTTAACCCATATTG CTGCT

CACTGTTCAAACCTCCAAGAGATTGATTTATACAGGTCTGTGGGAATTGGTGATACT GGATT

AGCAGCACTTGCCAGTGGTTGTCCAAAGCTCAGAATGGTCAATCTCTCATATTGTAT AGGTA

TCACAGATCATGGGCTGAAATCTCTGGCCCAACTAGAAAAACTTTACAACCTTGAGA TTCGG

GGTTGCTTCCTTGTAACATCTGCAGGGATTTCTGCCATTGCCTCGGGATGTAAGCGT CTGGT

AGAGTTGGATATCAAGAGGTGCTACCGTGTTGATGATATGGGAATGATGACTGTAGT TCAAT

GTTGCATAAACTTGAGACAGATAAATGTTTCATACTGTCCAATTTCAGATGCTGCCT TTTTGG

CATTGGTGAATCTTAGTTGCTTGCAAMCGTGAATCTAGTGCATCTCAGAAATGTTTC TTTGG

ATGCCTTTGCATATCTTTTGCTAGCTTGTGAGAGCCTAAAGAAAATCAAGCTTTTGA AACAAT

TAAAATCCTTACTTTCATCCAATTTAATTAGACATGTAGAAAATAAAGGCTGCAGAA TCCGAT

GGGTGGAGAAGCCTCTTTTTATTTAATTGTAGAAAATAGCTAAACTTTGATCCATGA AGACCT

CTTAATCCATGGTGAGAGCATGAGGTCTAATAAGTTCGGAACCGTGTATTCATCATC TCAAA

ATTGCAAAAGAATTTTCAAGTCCTGGTTTTTTGACCAGAAATTTTGTAAGGTAAGTT CTTGTCT

ATATGAAACTTTTTATTAGGATATTTAAGTTTCAATGGGTAATATTAAGTTTCAATG CTAAAAC

TTTTTATCAAAAAAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEu ID NO Sequence

147 GTCAAGGGTTCGATCTACGCTCGGACATCTTTGGCTCTGTTTCCCTCAGATTTCAGTGAT GG

AGGCCGCAGCAGCTCCAGTTCAATCGACGGACACGCTCATGTCCGACGCGCCGCAGG CCG

CCGGGTCGAATCCCATGGACAGCATCCCTGCAGTACTCAGTCACGGTGGCCGCTTCG TGC

AGTATMTATCTTTGGGAATATTTTTGAAGTCACAGCCAAGTACAAACCACCTCTGCT GCCTA

TCGGGAAAGGGGCTTACGGGATCGTCTGTTCTGCMTGMCTCTGAGACAAMGAGCAAG T

TGCCATAAAAAAGATAGCCAATGCCTTTGACMTCGCATAGATGCAAAGCGAACTCTT CGGG

AAATCMGTTGCTCCGACATATGGATCATGAAAATGTAGTTGCCATMGAGACATMTAC CTC

CTCCACAMGAGMGCCTTTGATGATGTATACATTGCATATGAGTTMTGGATACTGATC TCC

ATCAMTTATTCGCTCCMTCMGGCTTATCTGAGGAGCACTGTCAGTACTTTTTGTATC AGA

TTTTGCGAGGATTGAAATATATACACTCTGCAAATGTCCTTCATAGGGACTTGMGCC CAGC

AATCTTCTACTGAATGCAMTTGTGATCTGMGATATGTGATTTTGGGCTGGCTCGGAT TACT

TCTGAMCCGATTTCATGACCGAATATGTGGTTACCAGATGGTATAGAGCTCCAGMTT GCT

GCTGAATTCTGCAGATTATACTGCAGCCATTGATGTCTGGTCAGTAGGCTGTATTTT CATGG

MTTGATGAACAGACMCCCTTATTCCCTGGMGGGATCATGTGCATCAGCTGCGTTTAT TG

ACAGAGTTGATTGGCACACCMCTGAGGCTGACCTTGGATTTGTTCGGAGTGATMTGC TAG

MGATTTATTCGGCMCTGCCACAGTATCCGAGGCAGTCATTTACTCAAAMTTTCCTCA CGT

GCATGCATTAGCMTTGATCTTTGTGAAMAATGCTGACATTTGATCCAMTCAGAGGAT CAC

AGTGGMGAGGCACTTGCCCATCCGTACCTGGCAMTCTACATGATATCAGTGATGAAC CC

ATTTGTGCCATGCCATTCAGCTTTGATTTTGAGCAGCATACCTTMCAGAGGATCAGA TGAA

AGAGCTGATCTATAGAGAGGCTCTGGTTTTTMTCCAGAGTATGCACAGTAMGTMCAT TTT

GTGCAGACAGTGGTTACMCTTTGMMTTGGMGCTGGGCTATTTTCTTGTTTGTAGCAG T

CATAGTGTTATAMTATTTATTGAGTTTTGGGAGCMTGTAMTATGTGTATTAAMCCAC ATT

TGAGTCCAGGGCAAGTTGTMGGGGGATMTGATTGMGGGGTGTMAGCATTTATATTGG

AGTATGTCMCCTGATATGCTACMCTTGGTGAGATGCATTGTGCATGTATGAGTCACA GAC

CTGMCACTGCGGTAAMCTGTATTATGCTTTATTCTTCTTTATCTTCAMCTTCMGGGG TT

GTATGMGATAATTTTTGTTAGMTATMGTGMGMMGTTGAGTCTGGCAGTTTGCCACTT

TTGTCTMTTCTCCTTTCAGATMGTGATGMCTTGGACCTTTGGCTATTGTGTA

148 GTTGMGAAGATAAAAAATGGCAAAGMGCAGGCAGGGMGAGCMCGATAGCACTGTGAA

TGACAGTGGMGTGAAMTGAGACGMGMACCCGCCGGTTCGMGGAGGATGGGAGTATT

CATTCTCCTCTGGTTGCATACGCCTCCATTCTCAGCCTTCTCTCATGTACCCCTCCA TTCGTC

ATATTCCTGTGGTATACMTGGTTCACTTGGATGGATCTGCATCTCMTTTTGGGATTT ATGC

MGGAGCAAGGTCTTCAGGGTTTCCTMGMTCTGGCCAAMCCAACTCTCATAGCATGGM

ACTMTTGCATCATTTGCAGCTTTTGMGCAGCACTCCMCTACTTTTACCTGGTGAMGA GT

AACTGGACCTGTTTCTCCTGCAGGAMCATTCCAGTCTATMGGCAAACGGAGTGCTGG CTT

ACTTTGTCACATTGACMCTTATATTGCTATCTGGTGGTTTGGCCTATTTMTCCTGCM TTG

TCTATGACCACTTGGGAGAGATCTTCTCAGCACTTATCATAGGCAGCTTTATCTTTT GCATCT

TTTTATATATTMGGGACATGTTGCACCGTCTTCGACTGATTCAGGCTCCTCTGGAMT GTAG

TTATTGATTTCTATTGGGGTATGGAGCTTTATCCTCGMTAGGTAAAMCTTTGACATC MGG

TCTTCACAMTTGTCGGTTTGGMTGATGTCTTGGGCAGTTCTTGCAGTMCATACAGCA TM

AACAGTATGAAGAGTATGGMGAGTAGCGGATTCCATGTTAGTMGCAGTATATTGATG GTG

GTGTATGTAACAMGTTCTTCTTGTGGGMTCTGGCTACTGGMCACCATGGATATAGCT CA

TGATCGAGCTGGATTTTACATTTGTTGGGGATGTCTAGTTTGGGTTCCATCTGTATA TACATC

TCCAGCMTGTATCTTGTGCGTCATCCCATTAGTTTGGGTCTTMGCTGTCACTGGGCA TAC

TTATTGCTGGCATTGCATGCATATTCATCMCTATGATTGTGATAGGCAACGGCMTTA TTCC

GTAAMCAAATGGGMCTGCTTGATCTGGGGCCGACCACCATCAMGATAGAGGCTTGGT A

TGAMCCATGAGTGGGGAGMGAAGTCGAGCCTTCTTTTGACGTCTGGCTGGTGGAGTG TG

TCACGACATTTTCACTATGTGCCCGAMTTCTTGCGGCATTTTTCTGGACTTTGCCAG GACTT

TTCAATCATTTCCTTCCTTATTTCTATGTCATCTTTTTGACMTCCTCCTATTTGATC GAGCTC

MAGAGATGACCAMGATGCCGAGCAMGTATGGCAMTACTGGGATATATACTGCMGCM

GTTAMTACMTATTATTCCAGGMTTTATTGAGCMTTGGATAGTTTAGTTATGCTATGA CTG

GATTTCTCGGTCATTACTTMTGCAGCCTGTAGCTTAGTGGTAAGGCTGGTGACCACC GGC

GTTCGTATGGCTTMTTGAGCATGTGAAMTATCGGAATCGGMAAGCAGMTACATGTAG C

MCATATATTTTCGAMGCTCATCGAGCAGCTATAGAMCATTMTGCATGAMGAGATCTM

ATATTTAAAAAAAAM

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

149 AAGATCAGTTCTGGTAGTAGCTCCAACAATGAAGTTCCCAGCTCCGGCTAGGAATTTGTT GA

TAGTGTTGATAGTGTTTCTGGAGAGAATCCTTACCAGGTGTATGGTGAGTGATAGCT CAAAT

CATGAACCTCCAAGCTCATGTACTGCAACAAGGATCTCACCAGCTAGCTCTGGTATT ATCAG

TAACACAAAGCCAGCTGATTGCAGCTCGTTAGCTTCTTTGGATTTGCATGGGTCTAT CTCCT

TGCCTGGAACAGCAATTACAACCGAGGATTTTGGAGGAATCTACCACCACAAGCCAC TTGC

CATTGTGCATCCTGCGTCTGTGGAGGACATTGTGAAAGTAGTTACAATGGTGAATGC TTCTC

CTAATCTCACACTTGCAGCCATGGGAAATGGGCATTCCATAAATGGTCAGGCCCAGG CCTT

GAATGGGTTGGTTTTAGACATGAGGTCTCTCAAAGGAATTGAGATTTTCCAAGGAAG CCCAA

CGGAGGGTCCCTATGTCGATGCCTGCGGAGACGAGCTGTGGATTGATGTCCTCAAGG CTA

CTCTTCGCGTGGGCCTTGCTCCTCGTTCGTGGACTGATTATCTGCCTCTTTCTGTGG GTGG

GACACJCTCTAATGGCGGGGTTAGTGGCCAGACJTTTAAGTTTGGCCCACAAATCTC CAATG

TGTTGAATCTGCATGTTGTTTCAGGTAAGGGAGAATCCATGACTTGTTATCCCGAGA CGAAT

CAAGATCTCTTCTATGGAGCTCTAGGAGGATTGGGGCAATTTGGTATTATCACCAAA GCCAG

AATAATGCTGCAGAGAGCTCCTCACATGGTGAGGTGGATAAGAGCTGTATACGCAGA TTTC

GAGGAATTCAGAGCCGACCAAGAGCTGCTGATATCTTTACCAGAGGAGGGAACTTTT GACT

ATGTAGAAGGATTCGTTTTGACAAACAACGATGACCCAATCAATGGCTGGCCCTCAG TACTA

CTCTCGCCCTCAAATTCTTCCTTTGACTTCAAGCTCATACCCCAGACTGCAGGCCCA ATGCT

GTATTGCCTCGAGGTTGCCTTGCATTATGACCACGACGAAGATTTCGTCACTCTCAA TAAGA

GAATCGAGAGCATGCTAGCCCCACTCAGATTCATCAAGGGATTGCATTTCAGCTTTG ACTTG

CCCTACTTTGATTTCCTGAACCGGGTCCACGCTGCGGAAGTGGCAGCCAGATCGAGT GGAA

TATGGGATGCCCCCCACCCGTGGCTGAATCTCTTCGTCCCCAAGTCCAAAATCTCAG CGTTT

GATGCTAAAGTGTTTAGAGAGATTCTGAAAGATGGTGTGGGAGGACCCATCCTGGTA TATCC

AGTCACTAGAAACAAATGGGACTCTCGCATGTCTGCAATTATTCCAGAGGAGGACAC TTTCT

ACTTAGTGGCTCTACTCCGTTTTAGTCCACCGTATCCAAGTGGACCGCCAATTCAGA GCATT

CTAGCACAGAATGAACAGATTCTCCATTACTGTACAACTGCAGGCATTGACATGAAA TTATAT

CTTCCCCATTATAAAACAGAATCTGATTGGAAAAGACACTTTGGCAGGAAATGGCAA CAGTT

CCTGCAAAGAAAAAGCAAGTATGATCCAAAGGCTATCCTCGCTCCAGGACAGAGGAT TTTTT

CCAGGTCCACTGATTCAACAGCATTCACACGCTTATACTCATCATCGTGAAGACCAC TTTTG

CCCACCAATATATTCCCAAAGATTCAATCAAGATTTCATTACCCTTTGTACAGTCCT GAACCC

CATCTTTTTAGCTTTACACAAACCATCCATTATTCGGTCCTTGACTTTCTTTTTCTT GGGTCTG

CGATTCAGACCTTTTCTCGTATGGATGGATGCTACATTCAAACGGGCATATTCCACA TGACA

TTCTCTTGCATGGAGTTATCTTGTTGACTATGCTGCAACTGTTTTAAGGTGGGATGA TGCTGT

AACATCCATCACAGATTTCCAAGGAAGGTTATTTTGCAGGCAAACTGAATTTTGGCA GCTGC

TGGAAGATGCAGTCGTGAATGATGGGAGGGATCAATGCAAATTAGTACCATTCGACA GCTG

CCACCTGCCCATTGTTTGATTCCACGTGGCACAGAAGCAACCACATACTAGAAAATT GGACA

TCTTTTTTGGTTTATTGTAATTACAACCAGGTTCATGGTTGTTGGCTGCAAAAAAAA AA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

150 GGAAGTAAAGAGCCTCGGGTAAAAGCCTCACACCATGTCACCTTAAAACGCTGACAATTG G

AAAGCGTCACTATTAACTATTCAGCGCTATAATCAGCTCAATGACGTGGCAATGACA CGTAA

ATTTCAATGACGTGGTTAGTCACCATTCGGGTAACATCGAAGCAACAGTACTCCGTG GGTTC

TCTCAATCAAAGACATCATTCTCAAGCAATCTCGAAATCCCTGCATCCATACCTAAA ACCGTC

GCATAACATATATTGTCCCCGTAATTTGTCACAGTGGATATCCGGATAATTTGTCTC CGAGTG

TCGATTGATTTACAGCAATATGATGATTTTAAGTCTGGAATTCGGCGTCAGTGGTTA TGATCA

GGAACGGGTGAGAAAACAGCCCGGAATTCTCAGGCGTTAGGGCAAAAAAATGGCGGG GGA

ATTGACCCAAGCGGAGAAAGAAACCCTTGCTGCCGTTAATGTCGGGGCATCGGCATT ATCG

TTTGCAGGATCGGCTTTCATCGTGCTCTGTTATGTGCTTTTCAGAGAGCTTCGCAAG TTTTC

GTTCAAGCTGATATTCTACTTAGCATTATCTGACATGTTTTGCAGCCTTTTCAATAT ACTTGG

GGATCCAGGAAAGGGATTCTTCTGCTATGCACAAGGCTATACAACACATTTCGTTTG TGTTG

CATCTTTTCTTTGGACAACTACTATAGCTTTCACTCTCCATCGTACTGTTGTGAGAC ATAAAA

CTGATGTTGAAGAGCTCGGAGCCATATTTCATTTGTATGTATGGGGAACTTCACTTG TCATG

ACAATTATACCTTCGATTGGTGATGGCTATGGGCAAGCGGGTGCTTGGTGCTTGGTT AAAAC

AACATCAAGGGCTACAAAGGTCCTCCAATTTATTACTTTCTATGCTCCTCTATGGGG AGCAAT

TCTATTCAACGGTTTCACATACTTTCAAGTTAGTCGCATGCTTAACAATGCCACTCA GATGGC

AGCAGGCATGTCAGATCGGCAACAACAAACCGATTCAAGGGTTGATATGAAGGCAAT GAAC

CGATGGGGCTATTACCCATTGATATTGATAGGTTCTTGGACATTTGCCACTGTCAAT CGTATA

CATGATTTTATTGAACCACAAGAAAAGGTTTTTTGGCTTTCTTTTCTTGATGTTGGA ACAGCA

GCCTTGATGGGCTTGTTTAATTCAATTGCATATGGGCTAAATGCTTCAGTACGACGC ACTCT

TCAACAGAAAATTGATTTGTGGTGGCCAGAATGGTTTAGAAAGTGGCTACCTGGATT TATAA

TGCTGAGGGATCAGGCACATGAAAGTGAAATGATCTCACTTAAAATTCCAGTTGAAC AGTGA

TATCGTGTATTGTGTCTAGCTTTTACAGTATTAGGTCTCAACTTATTTTCAAGAAAT TACAAAT

CAATCCTTTTGGGAATTCGCTAAGGTTCAGCAGGTGCATCAAGATCAGATGATTCTA ATTCAT

CCTTCACTTGTTGAATTTCATCCATTTGTTTCCAGTCCCCTACGCTGACCTGAATGT AAATGG

AAGCCTCTCTATATATTTTAGAGTGTAGACTTTCATCTCTGCAGTGTCCAAGTGTTA CAGCTT

ATTATTTTGAAGTGAGTAACACCTAGACATGACATTGTACAACTTAAAGAACAATAG AAATTT

GCTCTATAATTGAAGGCAAAAAAAAAA

151 CGCACGAGGATTTTGTGTGACTTTATTTCTGAACTCTGTGAGGAGTCACTATTTTCAATG TAA

AGAGGTGGAGTCCAAAATCCATTTTTAAATTTTTCCCATAATAATAGTTTAGCCAGA TATCAT

CTGTCGGATGTATTTTTCCAAAAGCAAGAAACTGAACCACTAAATGATTTTTTTTTT TCATGAA

ACGCTGCTATGAAAATGGTTTCAGTGATCCTTTTTAATTTATACTTGGCTTGGTAAT GTATTCA

GGGTTTCCCCATTATATTTTGTGTTTGTTGGAGGTTTTTCCGGTTAAAACAACATTT AAAAAAA

AAAACTGCACACTAATTTAATGAAACCCGATACTTTTTGGTTCTGGAGACGTTCATA ATGCAC

TGTATGCTTTACAATACACAGCCATTCATACCCAGGGATCTCTTTATATTGATTCAC ACTCTT

ATACCTCCATGCCCTCTTACCCATATGGTAGGTTGTTGGGAATAAAAACTTAACGGT CCCAT

TCTGGCCTCTCACTATCATACCCAGTGAAAAATATATATCAGAGAGGGCACCCAATA GATAG

ATTGAGAGGATCATGGCATACAAAGCAGATGATGACTATGACTACCTGTTCAAAGTG GTGTT

GATAGGAGATTCAGGTGTTGGCAAGTCAAATCTGCTGTCCCGATTTACCAGGAACGA GTTCA

GCTTGGAGTCCAAGTCGACTATTGGTGTGGAATTTGCAACTCGCAGCATCATTGTGG ATGG

GAAAACGATCAAAGCCCAGATATGGGACACTGCAGGCCAAGAGAGGTACAGAGCCAT CACA

AGTGCATACTATCGGGGGGCTGTGGGTGCTTTATTGGTGTATGATATAACTCGGCAC ACTAC

TTTTGAAAGTGTGGAGAGATGGCTGAAGGAGCTTCAGGACCATACAGATAACAACAT TGtTG

TAATGCTCGTGGGTAATAAAGCTGACCTACGCCATTTGAGGGCTGTTTCCACTGAAG ATAGC

CAAGCCTTAGCTGAGAGAGAATCTCTCTATTTCATGGAGACATCGGCTTTGGAATCG ACAAA

TGTTGAGAATGCTTTCACGCAGGTTCTCACTCAAATCTATAGAATTGTTGTCAAGAA GGCTCT

TGATGTTAGTGAGGAGCCTTCTGCCCTTCCGCCACAAGGACAAGCAATAAATATCAA GGATG

ATGTTACAGCTACCAAGAAGCCAATGTGCTGTAATTTCTAGCAGGCAGAGGCAAGTT GTTAG

ATGATGCGGATATTTGAGCAGATTCTTTACAGTTGTAGTTGTTTGCACGAATTGTTG AGTAAC

TTCTTTACTCATTTGAGGGTTTCTCAGTTCTGATGACATATTTGGAGTCACATGAAT GCTCTA

TTGGCTGAGTTGACAAAATTAATTTCATCGGGTGTCTAGAATAGAATCAAGGAACAT AAATTT

GTAACTTATGATGAGTGATTTCAGCGATAAAAAAAAAAAAAAAAAAA ;

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

152 CAAATTTCAAGAλAAGGTTACTGTTTTCGCTTCCCAGGACGGACGGGCGGTCGGTCTGC AA

CACGCTTTAGAGTTTCAACTGAGATGCTTTCACACCCTTAATCCATGAATTGCTTCA CTCTTC

TTCCCTTCATTCCGCCATTCGTAGAGGTGCCTCGTTATATCTTGACGTTTTTCATTT CAGGTT

TTATGAGCTCAAGAAAGGGAAGAAACCCATTCATTTTCTCTTGTAAGCAGCGGGCGA AGGC

GGGATTGGGGTTTTTGTGTTAAAGGCATGCCGGGCAAGGGTTTTGTTAGGGACACGG TACT

TGACTGCTGCCTTGCAACACCTCGCATGCGATGACTCAGGGAATTAGAGCTTCTTGG TATTG

CACTTGGGCAGAGCAAGGAGCATTCGACTACCTTTGCTGAAACAACTTCGTTGTGAG ACAA

GCTTTGCAGTGATTGTATTCTATCTGATTTTGGACATGCTATGGCCTCTTGATGCAC TGCATT

GAATGTTGTTTCATGGGACATTGGGTTTTTACACATTCTCGTGTAGGAATGCGGAAG CAAGA

GTAACTGATTACTAAAATCTCATCAAGATGGAGTCATGTAACTGCATAGATCCGCCA TGGTC

AGCAGATGATCTGCTAACAAAATATCAATACATATCGGACTTCTTTATTGCACTTGC ATATTTT

TCTATTCCACTTGAACTCATCTATTTTGTGAAAAAGTCAGCAGTTTTTCCTTACAGA TGGGTG

TTAGTTCAATTTGGTGCATTTATTGTGCTTTGTGGAGCAACACACATGATAAACCTC TGGACT

TTTCATGTGCACACAAAAGCAGTTGCAATGGTTATGACTATATCTAAAATATTGACT GCCGTT

GTATCCTGTGCAACGGCTCTCATGCTTGTACATATCATACCAGATTTGTTGAGTGTA AAGAC

CCGAGAACTGTTTTTGAAAAATAAGGCAGCAGAGCTTGATAGGGAAATGGGTATAAT ACGGA

CACAGGAAGAAACTGGAAGGCATGTGAGGATGCTGACTCATGAAATCAGAAGTACCT TGGA

CAGGCATACAATTTTGAACACCACCCTTGTTGAACTGGGGAGAACTTTAGCTTTGGA GGAAT

GTGCTTTGTGGATGCCGACTCGAACTGGTTTGGAGCTTCAGCTATCCCACACTCTTC GACA

GCAAAATCCTATGACTTTTACCGTACCCATTCAACATCCTAGCATCAACCAAGTATT CAGTAC

AAATCGAGCAGTGATGATTTCTCCAAATAGTCCAGTAGCAATGATTCGACCACGGAC AGGCA

AGTACATGATTGGAGATGTGGTTGCAGTTCGTGTGCCCCTTCTGCATCTCTCAAACT TCCAG

ATTAATGATTGGCCAGAACCCTCAAAGAGATGGTATGCACTTATGGTCCTTATGCTG CCCTC

TGATAGTGCTCGCAGATGGCATGTTCATGAGTTGGAGCTTGTGGAGGTTGTTGCAGA TCAG

GTAGCGGTGGCTCTCTCACATGCGGCAATTTTGGAAGAATCAATGAGAGCACGAGAC CTGC

TCATGGAGCAAAATGTTGCACTTGAGATAGCTCGACAGGAGGCAGAAACAGCTATTC GCGC

TCGCAATGATTTCTTAGCAGTTATGAACCATGAGATGCGTACTCCGATGCATGCAAT TATTG

CTTTGTCATCGCTTCTTCAGGAGACAGAGTTGACTCCTGAACAACGATCCATGGTTG AGACC

ATCTTAAGGAGTAGTAATCTCCTTGCAACACTCATCAATGATGTTTTAGATCTTTCA AAGCTC

GAGGACGGGAGCTTGGAGCTAAACATTCGGATATTTAATCTCCGCAGTATGTTTCGT GAGGT

TCACAATTTGGTAAAGCCAATTGCATCTGTGAAGAAGTTGTGTGTATCAATGAATCT CGCTTC

AGACCTGCCAGAATACGCTGCCGGTGATGATAAACGTCTTATGCAAACTGTTTTAAA TGTGT

TAGGGAATGCTGTGAAGTTTTCTAAAGAAGGTAGTGTTTCAGTGACGGTTTTATTAG AGAGG

CCAGAATGCTTGCGAGATCCACGTGCCGAATTTTACCCAGTGCAGGGTGATCGCCAT TTCT

ATTTGAGAGTGCAGGTAAAGGACACTGGTGCTGGAATCAATCCTCCGGATATTCCAA AGCTT

TTTAGCAAATTTGTGCACTCTGACACAATGACAACCAGGAATTATGGTGGCACTGGT CTTGG

ACTAGCTATTTGTAAGAGGTTTGTGAACCTTATGGAGGGTCATATTTGGCTTGAGAG CGAGG

GATTAGGAAAGGGCTCAACTTGCATATTTATTGTTAAGCTTGGGATTCCAGATCCTA TACATG

AAATGGAGCATCAGTATGTGTTTCCCATTCCATCAAATTCTACCCGTAAAGATTTTC CTGGGC

TGAAAGTTCTGGTGACAGATGATAATGGGGTGAACCGGATGGTTACAAGGAGCCTTC TTGC

TCGTTTAGGGTGTGATGTGACAGTGGTGGATTCTGGTCATGAGTGCTTGCAAGCAAT GTCA

CAGGCTGGGCAGAATTTCAAGGTATTATTTCTTGACGTATGCATGCCGGGTATGGAT GGTTA

TGAAGTGGCCATTCACATTCAGGAGATGTTTCCTAATCGGCATGAAAGACCATTACT TGTGG

CTCTTACCGGAAGTGCTGACAAAGCAACCAAGGAAAAGTGCATAAAGATTGGAATGG ATGG

CGTGTTATTGAAACCAGTGTCTCTTGAAAAAATGCGTAGTGTACTAGTTGATCTCTT GGAACA

CGGGTCAGTATGTGACAGTATACAGAGGTTATGACCGTGTCTAAAAAGTGGAAGTTG GTACA

CGTAATGCTGTGCCATTGATCTTATGGATCTGACAAACAATGCACTGATTTATTCGT ATGAGA

CCAAAAAATCTCTGCAATCAATTTAACACAACAAAGTTTTGAGATTTACTAGATGCC AAATTTA

GTGATTTGCTAGCTCAGTAGTGAGCATATTTGGTCTTCTTCGAGTTGATGTACACTT CCCAG

CATCCTTTACATTGGCTAGTTGCTGATAACTGTGGGCTATTCTGCTTTGTCAGCAGT TACAAG

AACTGTTCAACCTTCTAGCAAATCTGTTGCCCTAAAATATTGCACTGTCTTTGAAGT GCCACG

CATGACATATGGAACTGTACAGTATAGTGGCTATATGCGACCTGAATGA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

153 CGAAATCTTCTCCCCGCCTGTCAAGTAACGGACGTGGGCGTCCATGTAAAGAGCAGAAGA A

ATGATGGCGATTCGGCTTTGATCAGAGAGGTCCCTATTGCTCAAATTTATCCCGCTG CGCCG

ACCCAATTCTTTGAAAATAAAAAATGTCGTTTCGAAAGCGCGCCCTGTTCAAGGTTA TTGTTC

TCGGTGACAGCGGGGTTGGAAAAACATCTTTGGTGACTCAGTATGTACATAAGAGAT TTAGT

AGCCAGTACAAAGCGACTATTGGTGCGGACTTTATGTCAAAGGAACTTCAGGTTGAT GACAG

ACTTGTAACATTGCAGATATGGGACACTGCTGGGCAGGAGAGATTCCAGAGCCTGGG TGTT

GCTTTCTACAGAGGTGCGGACTGCTGTGTACTTGTGTATGATGTAAATGTGCTCAAG TCATT

TGACAACCTGGAAAATTGGCACAAGGAGTTTCTGAATCAGGCCAGCCCAACAGAACC GGAC

ACTTTTCCATTTATGTTGCTGGGCAACAAAATTGATGTGGATGGGGGAAACAGTAGA GTGGT

TTCTGAGCTCAAAGCAATGACATGGTGTAAATCGAAAGGTATCCCCTATTTTGAAAC ATCAG

CTAAAGATGATTACCGCATTGATGCAGCATTCTTATCCATAGCCAGATCTGCACTTA AGAATC

AACCTGAACAGGAAATCTATTTTTTAGGCCTTCCTGAGGCTCTTCCTGAATCAGAGC CGCCA

TCACGCAGCTTTTGTGGATGCTAATGTCAGTGCAGGAGTATTGTCTTTTACATTGAT AAACAA

TTTTATAGGCATCTTCTTCTTATTCCCAATGGGAAATTTTTGGGCATTAACGGGTTG GTAGAT

TGTGTCTCAGTGAATAAGACCACCAAAATCATGACAGATGATCCAAGGTATCTCGTC ATGTC

CTTAAGAGCTTGGTTTCTCTTTCTATCCCAGTTTTTGTTCTTGGCCATTCGGTTT

154 GCGGTACATATATACACAGATACAACTAGATACCCTCTGAAGATTTTTGGGGTAATCTGC GA

TCATTTTCGTCCGGGAATTTTTTTGTTTGTTTTTAATTTTTGTGGGCTTTGATGCAT TTGAAGG

TACGTAGGACGTTTTAGTTTTTCCCTGTAGCTCCAAAATCGGCCATGGGGTCTGAAA TCTAA

GCGCTGTATGCATGAGGCATATTTGTTATTATTAGGATTGCAATTATTATTATGGTG GTGAGA

AGGATGAGCTCGTTCCCTGATGAACTGCTGGAGCACGTATTGGCATTCCTGTCGTCG CACA

GGGACAGGAACGCGGTTTCCCTGGTCTGCAAGTCGTGGTTTCGAATCGAGGCGGGCA GCA

GGCAGCGGGTTTTCATCGGAAATTGCTACGCGGTGAGCCCCGCTATACTCATCAGGA GGTT

CCCAAGGATAAAGTCCGTTGCGCTCAAGGGGAAGCCCCATTTTGCGGACTTTAACAT GGTG

CCCCCTGGCTGGGGCGCTGATATCCATCCCTGGCTGGCCGCCATGGCGGAGGCGTAC CCT

TGGCTGGAAGAACTCAGGCTTAAGCGCATGGTGATCACTGACGAGAGCCTTCAGCTC CTCG

CGCGTTCTTTTCCCAATTTCAAGGTTCTCGTGCTTACCAGTTGCGACGGCTTCAGCA CGGAT

GGGCTCGCTGCCATTGCTGCGCACTGCAGGCATATTACAGAGCTAGATTTGCAGGAG AGTG

ACATTGATGATCGTGGTGGCAATTGGCTAAGTTGTTTTCCGGACTCATGCACATCGC TTGTT

TCCTTAAACTTTGCATGTCTGACTAAGGAGGTGAACTTTGAAGCACTTGAGAGATTA GTAGC

AAGATGTACTTCTCTGAGGAGTTTGAAATTGAATCGTTTGGTGCCATTAGAGCTACT ACATC

GCCTTTTGGTTCGTGCCCCACATCTGGAGGATTTGGGTACAGGTGCATTCCTTCACG AGCC

ACGCACTGAACAATATTCCAAGCTTAAGGTTGCCTTACAGAATTGCAAGCGACTTCA AAGCT

TATCTGGTTTTTGGGAGGTTGCACCTGGTTATCTTCCCTTGGTTGAGTCCCTCTGTT CAAATT

TGACTAGTCTGAACTTGAGTTATGCAACAATTCAAAGTGCAGAACTTACCAACCTCC TTGGT

CACTGCCACAAACTACAGCGCTTATGGGTGTTGGATTATATTGAAGATAAAGGGCTT GAAGT

GGTTGCCTCAACCTGCAAAGATTTGCAGGAACTGCGTGTTTTCCCGTTAGACCCTTA TGGTC

AAGGAGCCGTGACAGAGGAAGGCCTTGTGACTATTTCAAGGGGCTGTCCTAAGTTGA CCTC

TGTACTATATTTTTGTTGTCAAATGACAAATGCAGCTTTGATTACTGTTGCAAGAAA TAGCCC

TCTTCTCACCTGTTTCCGCTTATGTATATTTGATCCCACAAGCCCAGATCATTTGAC AAAGCA

ACCCCTGGATGAAGGGTTTGGAACAGTTGTTCAGTCTTGCAAAAGTTTACGGCGTTT ATCTA

TGTCTGGCTTGCTTACAGACAAGGTCTTTCAGGTGATTGGTACTTATGGCAAGTGTT TGGAG

ATGCTTTCTGTTGCTTTTGCTGGTGATAGTGATTTTGGGATGCAATGTGTACTATCA GGCTGT

ATAAATCTCCGTAAGCTTGAGGTAAGGGACAGCCCATTTGGTGATTTAGCTCTTTTA GCAGG

TTCAGAAAAGTATGAATCAATGCGATCCCTTTGGATGTCATCCTGCTCTGTTACCGT GCATG

GTTGCAAGGAATTGGCTGCAAAAATGCGTAACTTGAATGTTGAAGTTATCCATGACA GGGAT

CAGTTTGAAGATATAAGTACCATGACTCAACCCGTAGATGGACTCTATGTGTACCGG TCAGT

TGCTGGACATCGGAAGGATACACCACATTTCATATACACTATGTAAGTGGTCATGTC ATTTCT

CATGTACCATGAATGAAGCTGGCATGTTCTTGCTAAAGCAGCAGAGTACCAAGCATG GATG

GGATTTTCCTCTCATACACCATGGATTATGCCAGAAAATTCTTGTGATACTGACACT TTCACC

TTCCATCGCAAAATTTGTATGCCTTGTACAGACAAATTTCAGCATTCAAATACTGTT TGGCAT

AGAGTTATTACTGTCATTTCAGCACTATGCGGCAGTATCCTCTAATCTAGGACTGTT CGATTG

ATCGTTGGACTCCCTTAATTATGCTACAGATTATTTAAATGCAGCAAATGAACAGCC TGGCA

GATTCCTAGTCTGGAATTAGGCAGTAAATAGTTATTTAATTATATAGGCATACAGTG TGATTT

CGTTTCATTTTTTAGAGAACCCTTCCGGTTACCGCTATTTAAGACTGCCATGTTCAG AAAATC

TTATTTGATTGAAGAGAAGACAACATTCTCTGCACTATTTCTTTCTAAAAAAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

155 AAATCACATAAAAACAGGGAGATTCGAAAGACGGTTTTCCTGTTGTCGGCACCATTGGAA AA

TTGAGCCAGGGTTCGAACAAGGGTTTGCAGGTTTCTCATCTCTTTAAGAGCCGTTTG ATACA

AGACTTCGCCAATTTAAACAGCAGATCTCTGGAGCTTTCAGGCCCGGAATTGTCCCA GCAAC

TCGTGCTCTGCGTAATGAAAAATGAGGAACCTTCTCCTAGATCAATGAGGAGAGACG ACGC

CAGGCCATAATTTGGCAATACATTCGACATAGTTTACAGTATATTACCAGTTCCATC GATTCC

AGAATTTATATTTTGACAAAATCAAGAACTAACTCCCAAAGGCAATTGCATGGTTTG ATTCTG

GGATAGTAGTTCTCCAACTCCATCTGGACTGAACACTAAATATAACCACAAAAGTCA AAAGT

CATGGCACAGCAATCCTTAATATACAGTTTTGTGGCCAGGGGAAACATTGTACTTGC AGAGC

ATACATCATTTTCGGGGAATTTTAGTATTATTGCTGTCCAGTGCCTGCAAAAGCTGC CCTCAA

ACAGCAACAAGTTCACATACACATGTGATAACCACACATTCAATTACCTCGTGGATG ATGGA

TTTGTGTTTCTTGTTGTTGCAGATGAAGCTGCAGGAAGGCAGGTGCCTTTTATTTTC TTGGA

GAGAGTAAAGGAAGATTTTAAGCGGCGTTATGGAGGAAGGGCTGAGACAAGCATGGC GCA

CAGCCTTGATAAGGACTACGGGCCAATACTGAGAGACCACATGCAATATTGCATGGA CCAT

CCAGAGGAACTAAGCAAGTTTTTTAAAATAAAGGCTCAGGTTTCAGAAGTGAAAGGA ATTAT

GATGGACAATATTGAGAAGGTTCTGGACCGAGGTGAAAAGATCGAACTTCTTGTAGA TAAGA

CAGAAGGCTTGCAATTTCAGGCTGATAATTTCCAGCGCCAAGGAAGACAGCTTCGAC GGAA

GATGTGGCTCCAAAATTTAAAATTCAAATTGATTGTGTTGGGTATCGTACTAGTTAT TATGCT

TATAATATGGTTGTCCATTTGTAAGGGATTTAGTTGCCATTGACATCTAAGTGGTTT TATGTA

CATATAAGAAACTGGCATGTTTATGAGTGGAACAACTTTTTGTATATCATGAAGGTG AATAAG

AATTAAGAACACAACGAGCTAAATGAATTGATAGGGGAGGAAATGCTCATATTGAGT CACAT

TTGATGTAAAAAAAAAA

156 GAGATTCTGAGTCAGGTTCAATACTAAATCATTTCTGTACGAGCGAGTTATGTGTGGTTT GC

GGAAAATGACAGAAGATTAGAAAACGAAAGAGCAGATTTCAATGACTGGACGACGAG GAAA

AGGAGATAAACAACGTCACACAAAATGAAAATGTGGAGGGGATGGCATTTTACTGGG TGAG

GTCTCCCACAAGGAGAATTGTAGCAGCTCTTCTTCTGGGGGGCGGAATTGGGTGTTT TGTG

TGGGGTGCTCACCTCTCCTACCAAAACGTGGCTCCCCAACAGGCTCGCATACAGAAG CGCA

ACGAGTTCATCCGAAAACGCCTGCAGGCGCGACGATCGGGCAACTAGCCTAACGACC GAC

TAATGTTTGATTCCAACTAGCCTACGGTGAATAGAATCGTCGTAATTATCGTCATCA TCAGCA

GCAATGTCTATTATAAGCATCCCCGAAGTGGAAGTTGAAATGGGCTCGGCATCGCCT AACG

CCAGGACTCTTCGAGCCACTGTTGTTCAGGCCTCCACTGTCTTCTACGACACCCCTG CTACT

CTCGATAAAGCAGAAAGATTGATAGCAGAAGGTGCTGCTTATGGGTCACAGTTGCTT GTGTT

TCCTGAAGCTTTTATTGGTGGCTATCCTCGAGGTTCTAATTTTGGTGCTGTAATTGG AAATCG

CACTTTTAAGGGTCGGGAGGAGTTTCGTAAATACCATGCTTCTGCTATTGATGTGCC AGGTC

CAGAAGTAGAGAGGATATCAGCTGCAGCTGCAAAATATAAAGTGCATGTAATAATGG GTGTG

ATAGAGCGAGCAGGCTTCACACTGTATTGCACTGTTCTTTTCTTTGATTCTCAAGGA AGATTC

CTAGGGAAGCACCGTAAACTGATGCCAACATCTTTGGAGCGTGTGATTTGGGGTTTT GGTG

ATGGATCTACCTTACCTGTGTATGACACATCAATTGGGCGTGTGGGTGCACTCATAT GCTGG

GAAAACCGAATGCCTCTTTTGAGAACAGCTTTGTATGGAAAAGGAGTGGAACTCTAT TGTGC

ACCAACTGCTGATGCAAGAGAGTCATGGCAGGCATCAATGCTTCATATAGCTCTGGA GGGT

GGATGCTTTGTGCTCTCAGCTAATCAGTTCTGCAGAAGAAAGGACTACCCTCCTCCA CCAGA

CTATGTCTTTGGAGGTTCAGAGGAGAATATGTCTCCAGAGAGTGTTGTATGTGCGGG TGGA

AGTGTTATTATTTCTCCTACTGGTACTGTATTGGCAGGGCCCAATTTTGAAGGGGAG GCTCT

AATTACTGCAGATCTTGATTTTGGTGAAATAGTGCGAGCAAAATTTGATTTTGATGT GGTTGG

GCACTATGCAAGACCTGAAGTGTTGAAATTGACGGTAAATGACTATCCATTGAATCC TGTCA

CATTTTCTTCAGGGATAGCAGCATCAGAAAAAAAGGACAGTGAGAATGTGTAAATTT AATCT

GCAAGCATGGCCAAGGCCCAGTACATTCAGATGCTCCCTGAATGGATTTCAGAATTG TCTTA

ATGGCCAACTATGCTACCATATGGCATGATGAATAGGCTCGAGCATGAGTAGAAGGA ACTAT

TTGTTATTGAAAAACAGTTGTTTAAGTATCCAAAATGTATAACTACAGAGACCATCT TTTCTGT

AAAACTTATCTTTGTATATAACAAGATTGAGCATGCCTAGAATAGAAAGAACAATTT GTTATTG

AGTAATCAGGGAAACATTTGTATAAGTATTCAAAATGTAGAACTACAGACACCATAG CTTTGT

AATGATTTATATTTGCATATAGCAAAATATAGACATTATTTTACGGAAAAAAAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

157 GCGCTCCCGTGGGAAACAAATGCTCAGAGATCCCCACACTGCCCTACATTGAGCCGTTCA G

CAGCTAAAAGTCCCTTACATTTCACTTTAAGCTCTACCCATTTCATTTCTGCGCTTT AACAAG

CCCCCTGTGTGCGTTTCTAGTAGCAATGGAGGACGATCCTGGTGAAGATTACTTGTT CAAG

GTGGTGTTGATAGGGGATTCTGCAGTGGGGAAGTCGAATCTGCTGTCGAGGTATGCC AGGA

ATGAGTTTCACATGAATTCCAAGGCCACAATAGGTGTGGAATTCCAGACTCAGAGTA TGGAG

TTTGATGGGAAGGAGATCAAGGCACAAATATGGGACACTGCAGGCCAGGAAAGGTTC CGG

GCTGTCACTTCTGCTTACTATAGGGGAGCTGTTGGTGCCCTCGTTGTTTATGATATC AGCAG

GAGGCACACATTTGAGAGTGTGGGTCGTTGGCTTGATGAGCTCAAAATGCATTCCGA CATG

MTGTTGTTACAATGTTGGTTGGCAACAAATGTGATTTGGAGTCTCTGAGAGAGGTAC CAGT

TGAAGAAAGCAAAGCCCTTGCTGAAGCAGAGAAGCTGTTTTTCATAGAAAGTTCAGC ATTAA

ATGCGACAAATGTGAATGATGCCTTTCAGATTGTAATCAAGGAGGTTTACAATAACA TGAGT

CGTAAAGCCTTAAACTCAGGTTCTTACAAATCTAAATTGCTATCAAACGGAAGCACT AGTGTC

AACCTTGTGCAGAATGGGGATGCTGCAACAAAGACAGGGTTAAAAAAGTATGGTTGC TGCT

GAAATCAAATCTCTTTTTTCCTCATGGGTTCCAAATTTACTTTATTTAATCAAATCT GCAGTGT

TAACCACCTGTTATCTACATGGGATTCTTACAAGCTATTCTTCATTTTCAGTTGTAA TAAAAAT

GGAAGCATCTTGGATGTATTGTGTTGACAGTCAAGCTTGTAGGGTCCTCTGTTTTTG ATCTG

CATGTGGAGAGGAATCGGAAGTTTTGTTTGTCTATTTGTGGAGGATCTATGACATTT GCTGG

ATCCTAATGCTCCATGTATTCATCAGTGTTTTTATAGAAGTAATGT

158 GATCTGCACTCCTCTGTGATTGCTTCTTTTAAGTGTTTTTTGGGTTTGAATTTGCCTTTA TACA

AAGATGGCAGTGCCCGTTATTGACATAAAGAAGCTGCTGGATGGAGAAGAAAGGGAG ATGA

CCATGGACCAGATACACAAAGCCTGCCAAGAATGGGGTTTCTTTCAGCTTGTTAACC ACGG

CATACCGTACAGTCTTCTTGATAGAGTGAAGGTATTGTTCAAAGAGCATTACAAGAA TTCTAT

GGACGCGCAGTTTCAGGATTCTGCAGTTGTGCAAATGCTTGAAAGTTCTAACTCCCA AGGCA

TGAATCTCAGTGCCACTAAAATAGACGCCGACTGGGAAACGGGCTTCTTCCTCCCAC TCTC

GTCGCATAAAACAGAAACAGTGACACCGCCTCTGCCTGCCAACTTCAGGGAGACGAT GGAG

GAGTTTGCAGAGGAGGTGAAGGGATTGGCGGAAAGATTATTAGAAATAATGTGCGAA AATC

TGGGACTGGAGAAAGTATATCTGAAGGAAGCCCTGGCAGGTGGCAATGGTGATAACA ATAG

CCCTTTCTTTGGCATAAAAATGTCTCACTATCCACCATGCCCAAGGCCAGACCTTAT TGACG

GCCTCCGAAACCACACGGACGCCGGTGGACTTATTCTGTTGCTACAAGATGATGAAA TCGA

CGGCCTTCAAGTTCTGATGGACGGCACTTGGTTCGACGTACAACCCATTCAACATGC AATTG

TTATCGACATAGGCGATCAGCTGGAGGTGATGACGAATGGGAAATATAAGAGCATGT GGCA

TCGTGTGCTTGCTAAAGAGGACGCAACAAGAATGTCAGTAGCAGCGTTTTATAACCC TTCGA

GTGATGCAGAGGTGTATCCTGCTTCGCAGCTGATGTCAGCAGAGCAGAATGGAAGTA ACAA

TGTTAATGCAGAAAGTGGTTATGATTATCCAAAGTTCGTATCCGCAGATTACATGAC AGTGTA

TGCTGCGCAGAAGTTCCTGCCCAAAGAACCGCGATTTGAGGCGATGAGATCAGTAGG TCAT

GCCGTGAATTGAGCAGCAATCCACATGGAATTTATAAGGATAATAAAATCAAACTAA AGTAAT

TAAAAAAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

159 GTTCTACTTAGCCCTGTGGCTTCTGCCTACAGGATCAAGTATCCATCTTTGTTCTCTTCT GCT

TTGGGTATATTTGTTGAGTATCCATCTTGTCAGTTTGTAATTTGGTTTTTAATATTT TTTGACT

GGAGGGATTAGGGATGGCCACCAAGGTGGATCCTCCGAATGGGGTTGCTGCAGAGGG GAA

GCACTACTATTCCATGTGGCGCAACACGTTTGAGATAGACACCAAGTATATTCCCAT CAAGC

CCATTGGGAAGGGTGCATACGGGATTGTGTGCTCGGCTAAAAACACAGAGACCAACG AGAA

AGTGGCTATTAAGAAGATCGGCAACGTATTCGAGAACCGGATCGATGCCATGAGGAC ACTT

CGGGAAATCAAGCTTCTCAGGCAGCTCGCTCATGATAACATAATTACCTTGAAGGAC ATCAT

GACCCCTGTTGGCAGGTCTAATTTCAGGGATGTTTATCTGGTTTATGATCTCATGGA TACTG

ACCTTCACCAGATCATCAAGTCTTCTCAGGCCCTCACTGATGATCACTACCAGTACT TCATCT

ACCAGTTGCTGCGAGGCCTAAAATATTTGCATTCTGCCAACGTGTTGCATAGAGATT TGAAG

CCAAGTAATCTATTATTGACTGCCAATTGTGACCTTAAGATATGTGATTTTGGTTTA GCTCGA

ACAAACTGTGAGACAGGGCAGTTCATGACTGAATATGTTGTCACTCGATGGTATAGG GCTCC

TGAATTGCTTCTGTCCTGTGATGAGTATGGTCCATCTATTGATGTGTGGTCTGTAGG CTGTA

TTTTGGCAGAGTTGTTGGGCCGACAGCCAATATTCCCTGGTAAGGATTATATCAATC AACTT

AAACTGATCATCAATGTTATTGGCAGCCCAGCGGAAGATGATCTTTACTTTGTCCAG AGCCA

GAAGGCCTGCAGCTACATCAAATCACTTCCTCATGTTCCCTCTGCTTCTCTGCAACG TTTATA

TCCTCAGGCAAATCCTACTGCCATCGACCTACTAGATAAGATGCTAGTTTTTGATCC TTACAA

GAGGATCACTGTTACAGAGGCTCTTGAGCATCCATACTTCTCTGCGTTACATGATCC AAGGC

TCGAGCCTTCTGCAACAGCACCTTTTGAATTGGACATGCCTGATGAGGAATTGAGAG TACAG

GAATTGAGGGAGATGGTCTGGAAAGAAATGCTATATTATCATCCAGAAGCTGCAAAT ATATT

ATAGATACACAAAATTATCCATTTGTTTTTTGTTGGATAACTTCATGGATGAGAAGA TGAGAT

GTAGAGATGGATAAAGTTTGAATATATCTCAAAGCACGGCCTTGAGTTTTGTTCAAA AAAAAA

A

160 GAAAAGACATTCCCGTGTATTGAATTGGGAAGCAATGGGAATCGAACTAGAGATGGACAG A

CCCCAGGAAGAGGGCTGGGTGAGGGGTGCCATTCTTGGGGCCGGAGCTTACGGAACA GTC

AGCCTTGGCGTGAGCAGGTCCAATGGCCAACTCTTTGCAATCAAATCTGCAGCCGGC TTTA

GTGTCGCTTTGGAAAATGAGTACCAGATTTTGCGGTGCCTCGATTGTCCATACATCG TTCGC

TGCCTGGGGCACAATTACAGCTTCGAAAACGGTGCAGAGGTGCACAATTTATTCTTA GAGTA

CATGCCAGGTGGCAGCTTGGTGGATCTACTGGGAAGGTTTGGAGGGACGCTGAACGA AAC

AGTGATCAGAGCATACACACGCGGCATCCTGCGTGGACTCGATTACCTACACAGTCA GGGG

ATTGTGCACTGTGATATCAAGGGGAAGAACATTCTTGTGGATTCCAATGGTGTGAAG CTTGC

TGACTTTGGTTCTGCTAAGAGGGTTGATGATGAGGAGAAGTGCGAGGAGGCCATGCA ATTG

AGGGGAACCCCTCAGTGGATGGCTCCAGAGGTGGTGAATCAGGTGGAGCAGGGGCCT GCT

TCTGATATTTGGTCTCTCGCCTGCACTGTGCTTGAAATGGCCACTGGCAGGCCTCCA TGGA

GCCACGTTTCCAGTCCCCTTGCCGCAATGTATCGAATTGGATGCACAGAGGAGCTGC CTGG

GTTGCCTGGATGTCTTTCACCTCAGATTCGGGATTTCCTAGAGAAATGCTTTCGGAG AGATC

CTAAGAAGAGGTGGAGCAGTGCAGAGCTGTTGAACCATCCTTTCTTAAAAAAGGACT GCTCT

GTTATTGAGGCAGAGGAGGCCATTAGGGGTCCGGGATCTCCCACTAGTCATTTGGAT TTTA

GGAATCACATATGGGATTCCTACTGTTCTCAGACGACTCTCATTCCGTCACTCAGTC TCCCA

AGCCCAACTAGGGAACGCAATGCAGAGGTGAATAGATCAGTTGAGCAATGCCCAAGG CGTT

CTCCCAGAGACAGATTGATGGCACTGGCCGCAGCTTGTAAATTTGAAAAAGTTGCGA ACAG

GCCTAATTGGATCACAAGCCTCCATGGTCCATGGACTGTTGTGAAATCTTCCAGAAG TAAAT

CTCCAACTTCAGATAAGCCTCTGTTAAAATCAGACATTAGTAATGGCTCCTCCATCC AGGAG

CTTCCATTTACGGAAGAMGGTGCAGTACCAGCTTCAAAGCTGTCAATTGGAAAGGGT TGCA

GCCMGAGGTGMCTAGATCMTGCTCACAGGCTATGCTCTCTTCAGCCCMTCTCAACAT C

MCCATCTTCCAGCACTTCTTCCMGACTCCGCATCATMCTTGTTTTCGCTGGCTGAGA CA

TCCMTTTGACTGGTGMGCTTGGGMTCGGATGGAMTTCATCTCAGAGGATTGTTGGTG G

TGATTAGTAGTTGMGAAACGCTTTATATGTTTGATGATAAGCGTMGTCTACGACTTG TGCA

GGAGCMCTTACTGCCCCTGTCGCTGTATGCGMCTCCACMTTTTGTCATACMGTATCA G

MATCTGTAGTTGTATAGTAGCCGCAGAGCAGATACATGCTCTTGTAATTTTGATTCA AAATT

MTACCGGTTGAGTTTGTTCGGTTACACTAGCCGCAGAGCAGATACATGCTCTTGTMT TTT

GATTCAAAATTMTACCGGTTGAGTTTGTTCGGTTACACMTATATGACTTCATGATTA GCCA

TTTMCTTAAAAAAAAM

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

161 GTCGCTGCTCCTCCCGCTACGGλAATTTCTTCCCTATTTGAACCCCTTTCGAGCCACTG GTT

TTCCAAGGACCATACTGCGCCTTCTGCTGCTTCGCTTCTTGTGATTTTGCATTTCAG ACTCTA

ATCAAGTTTGTATCCATTGAACAACAACAAAAAATGTCGGGTCGCAGAAATCCGCTG TTGAA

TATCCCAATTCCTGCTCGGCAACAGACTCAGCTGTATCGACTTCCTCTGCCTCCGCA GAGCA

CATCTGTGTCCAGAGACGTTTCGGATCTTGCAGACTTGGAGCGAATTCAGATTCTCG GCCAT

GGAAGCGAGGGCAATGTGTACAAGGTCCGACACAGGAGGACTTCGGAACTTTATGCC CTGA

AGGTCATCCATGGCAATCACGACGAGACTGTGAGGCAGCAGATAATCCGACAAATGG AGAT

TCTGAAGAAAACAGAGTCCCCGTATGTGGTGAAATGTCACGGGATTTTCGAAAGGGG GGAA

GAGATCCACTTCGTGCTGGAGTACATGGACGGAGGGTCGCTGGAACAGAGGAGATCC GAC

ACCATGTCGGAAAGATTTCTGGCAGAGGTAGCAAGGCAGGTCTTGGAGGGTTTGAAA TATC

TGCACCGTCACAAGATCGTGCACAGAGACATAAAGCCCTCAAATCTGCTCATAAACA GGAG

ACAAGAAGTGAAAATTGCAGACTTTGGGGTTAGCAGAATTCTGTCTCAGACATTGGA TCCCT

GTAATACTTATGTGGGTACCTGTGCCTACATGAGCCCCGAGAGATTCGACCCCGAGA CCTA

CGGCGGACGGTACGATGGATACGCGGGCGATATATGGAGCTTGGGGTTGAGTCTGCT GGA

GTGCTATACTGGGCATTTCCCGTTTCTGGCAGCAGGGCAGAAGGCGGACTGGCCGGC CCT

GATGTGCGCAATCTGTTACGGGGATCCCCCGGCTCCTCCTCCCACGGCATCTGCCCA TTTC

CGGAGCTTCATCACATGCTGCCTGCACAAAGATGCCCGCAACAGATGGACCGCTGCT CAGC

TCTTGGGGCACCCTTTTGTGCTGTCAAATCCCCCCCAGACACCCTCCATTCCTATGC AGAG

GCTCTCCATCTGATCCAATGTTCCCCATGCGCAAATTACTCTGAACACATGAGATGA AATAA

AACTGCATGTGTATGAATCTATGATCTGTCTAATAACTTGGGTAAATTTTGTTCAAA TACCTG

GTTTTGGTTTTCGTTTTGTTTAAAAAAAAAA

162 CATTCATCCATCATGCATTCTGCCTATCCATCTTCCCCGAAACCGTTGCATCCCTGCCTC TTC

ATTTCATAGTCTCCTTCCATGCACATCTTAACTAACACATACACATTGTATATACAT CTTTTCC

GTAGTACCCACTTCTCTGCCCTGCTGCTGCTGCTACTGCAACATCCTCCCGTGCACA GCCC

TTATACGACACACACACATCGAGTAACCAGACCCTCGGCTCCCGTTTTAGGCATATG CACGT

CGAGTATCGATCCATCTGCTCAGTCTGCAGTTTGAAATTTTCGATTATTTGTTTCTG ATTCGG

AAGGATGGCCACCAGGGTGAATCCGCCTAACGGAGTGTTTGTGGAGGGGAAACACTA CTAT

TCGATGTGGCGCAACATATTCGAGTTAGACGCCAAGTATATTCCCATCAAACCTATT GGGAA

GGGCGCCTATGGAATTGTTTGCTCGGCCAGAAACGCAGAGACCAACGAGAAAATTGC CATT

AAGAAGATCATCAATGCATTCGAGAACCAGACCGATGCGAGGAGGACGCTCAGGGAA ATCA

AGCTTCTCAGGCTGTTCGCCCATGATAATATAATTGCCTTGAAGGATATCATGACCC CTGTT

ACTAGAACTAATTTCAATGATGTTTATCTGGTCTATGATCTTATGGACACTGACCTA CACCAG

ATCATCAAGTCTTCTCAGGTCCTCACTGATGATCATTGCCAGTACTTCATCTATCAG TTGCTG

CGAGGACTAAAGTATCTGCATTCTGCCAATGTGTTGCATAGAGATTTGAAGCCAAGT AATCT

ATTATTGAATGCCAATTGTGACCTTAAGATATGTGATTTTGGCTTAGCTCGAACAAA CTGTGA

GAAAGGACAGTTCATGACTGAATATGTTGTCACACGATGGTACAGGGCTCCTGAATT GCTTC

TGTCCTGTGAGGAATATGGTACATCTATTGATATTTGGTCTGTAGGCTGTATATTTG CAGAGT

TATTGGGACGAAAGCCCATATTCCCTGGTAAGGATTATATCAACCAACTTAAACTGA TTGTCA

ATGTACTTGGCAGCCCAGATGAAGATGATCTAGAATTTATCGAGAGCCAGAAGGCCC GCTC

CTACATAAAATCACTTCCTGTTACTTCCCATGCTTCTGTACAACGTTTATACCCTCG AGCAAA

TCCTTCTGCCATCAGCCTACTAGACAAGATGCTAGCTTTTGATCCTCGCAAAAGAAT CACTG

TTACAGAAGCTCTTGAGCACCCTTACTTTTCTGCACTTCATGATCCAAGCCTAGAGC GTTCT

GCAACAGCTCCCTTTGATTTGGACATGCCGGAGGAAGAACTGAAAGAGGAAGAATTG AAGG

AGATGTTCTGGAACGAAATGCTACATTATCATCCGGAAGCTGCAAATACATCATAGA TAGGT

GTAAAAATGTCTATTGTCTTGTGTTGGATGACTTCATGGAGGAGAAGATGAGACAGA AAGAT

GGCCTGGCTGATGGGACAGAAAGATGGCCTGGCTTTGAATTATATCTTGAAGTGTGG CGAG

AAGTTTTGTTCAATATTGTACATGTATACAATTTCAATTTGTGCTTTCTCTCTGGAA TTTTTCT

GAGAATTGCGGACTTTTATTTTCAATGCTCTGAAAGTATGAAGAGAGAGCGAGTCTT TTATAA

CAGGTTATTTTATTGTAAGAAAGCACACTTGTTTATGTGTAATTTATTCATCATATT CCCATTG

TAAATAAGATGGACTGCTAGTTGTCTAAATCAATAATATACTCTTTGATAAAAAAAA AAAAAAA

AAAAAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

163 GCTCCAGAATCCACTAGTCTTTTCCACATGCACGGTCCAGTCCTCAGTGTTCACCCATAA GG

ACACCCCATGTTTGTTAATGTATCCAGCAGACTATCTGCCTTATCTTGCCTTGCCGA GCCTG

CTGTAAAGCCACTATCCCAGACCATGACCATGTTTTCTTTATTGTTTTCTTGTCTGC TAGCTC

GCCCATAAGACCTGCCTGTCCCCTTCCGAGCACTGCATGTTTTTTGTCTCATCCCCT GTATC

ATGAACCACAATCTTTTAGAATATACAACTCTCGCTCTGCTCTTTCTCAGCGCCTGC AACACC

CACCTTGATTTCTGCAATCTCCTCTGCTGCATTTCTTCTTATCTTCTGAACTTCATT GAAGGC

CTACTACACTTCTACATATGAATGGCTTCATGTCTTTGCTCCCCTCTCTCAACTGCA TGAACT

GTTGTTATTCTTGGGAGGATTGAGGAGATCTAGGTTCTTCTTGACCATACTACTCAG CTTTGT

TGAAATGTACTCGAGAACTTCATAATGGACTCCACCATGCCCGGTCTTGTCCCCACC CGTCG

AGTAGGTACTGCTTATTGAGTATGCTATCAGATTCGGCCCCAGAATCTCATCTCCAC GCTTT

CCAAGGCTTCAGAAAGCTATAACTGATGTGGGTGTGGTGAAATCTCATCCCCATACT TTTAA

AGGCCGTTCACAGAGCTCGGGACTGATGTGGGTGTGGCGAAATCTCATTTCCATACT TTTAA

AAGGCCTGTCACAGAGCTTGGGACTGATGTGGGTCTGGTGAAATCTCGTTTTCATAC CATCA

CTGAGCTGGAAACTGACACGGTTATGGTGATAGAAGCCATCCATGGTGCTAAAAGTC AATAC

TAAGGAGACCCACCAGCGAAAACAATGCTGGTAGTTCTTGCAAATGGTTGTTGGCTT TAGCT

TTTCAGTCATTCGATGACTACAGACGATGAGAAGGGTGCCCAGATGGCCCAAATGAG ACAG

GAACATTCAGAAAACCCTGAGGAGGAGGAGGAGCGTGTGAGCTTTGATCTGAACTCC ATGT

GCAAGTTTTCATCCCAGAGTGACACAGAACCCATTGAAACCTCCTTCCCCGATGAAG TTCTC

GAGCATGTGCTTGTGTTTCTGACAGCCCACAAGGACAGAAATGCAGTTTCTCTGGTC TGCAA

ATCGTGGTACAGAGTAGAGGCTTGGACTCGACACCAGGTCTTTATAGGGAACTGTTA TGCT

CTTTCGCCTGGGACTATGATTAACAGGTTCCCCAAGATAAAGTCCGTGACATTGAAG GGTAA

ACCTAGATTTGCGGATTTCAATCTGGTGCCTCCGAACTGGGGAGCCCATCTGCATCC ATGG

GTTTTGGCCATGGCTCCGGCCTATCCATGGCTGGAGAAGCTGTTATTGAAGAGGATG ACTG

TTACAGACGAAGATCTGGCTCTGCTTGCCGACTCTTTCCCAAACTTTAAGGACTTAG TACTG

CTTTACTGTGATGGATTCAGCACCAAGGGCCTTGGTATAATTGCAAGCAAGTGCAGA CAATT

AAGACGACTTGATCTGAATGAAGATGATATTGTCGATAGTGGAGTTGATTGGTTGAG CTGCT

TTCCAGAAACAACTACCACTTTAGAATGCCTTAGTTTTGAATGTTTGGAGGGCCCGA TAAATA

TTGATGCACTTGAAAGATTGGTGGCACGTTGCTTGTCTCTAAAAGAACTAAGGCTGA ATAGG

ACTATCTCTATAGTGCAGCTGCATCGACTTATGTTGAGAGCCCCACAACTTACACAT TTAGG

AACAGGCTGTTTCTCCTATGATTTTATACCGGAGCAAGCAACAGTTCTTCAGGTTGC CTTCA

ACAATTGCAAGTCA ' CTTCAGTGTTTGTCAGGATTTCGGGAAGTTGTTCCTGAGTATCTACCA

ACAATCTATTCTGTTTGCAATAACTTACTGGAGCTGAACTTGAGTTATGCTGTTATG GGTAGC

AGGGAGTTGGAGCAGATTGTCTGCAATTGTCCAAAATTGCAGCGTCTTTGGGTTTTA GACTC

AGTGGAAGATGCAGGTCTACGGGCTGCTGCTGCAACCTGTAAGGACTTGAGGGATCT CCGA

GTTTTCCCCATGGATGCAAGAGAGGATGGGAATGGTTGTGTATCTGATGAGGGTCTG GTTG

CCATTTCAGAAGGATGTCCAAATCTCCAGTCGATACTTTACTTTTGTCAGCGTATGA CAAATG

CAGCAGTTGTGACCATGTCAAAAAACTGTCAGAACCTTACCAGCTTTCGACTCTGTA TCATG

GGTCGGCACAAACCTGATCATATTACTCATAAACCAATGGATGAAGGATTTGGTGCC ATTGT

AATGAACTGCAAAAAACTGACGAGGTTGGCAGTGTCTGGCCTTCTGACCAATAAAGC ATTTG

AATACATTGGGACATATGGAGAATCATTAGAGACCTTATCAGTGGCATTTGCTGGGG AGAAT

GATTTAGGCATGAAGTATGTTCTTGATGGATGCAGACGTCTACGGAAGCTTGAAATA AGGGA

CAGCCCTTTTGGAGATACTGCCCTTTTGTCTGGTTTACATCATTATGAGCAAATGCG ATTTTT

ATGGATGTCTGATTGCAAGGTCAGTATACAGGGTTGCATGGAGCTAGCAAGAAAAAT GCCC

TGGCTGAATGTGGAAATAATCAGAGAAAATAGCTACGATGACCGCCTTGTGGAAAAA CTTTA

TGTATATCGTTCTGTAGCAGGGCCTCGTAAAGACATGCCACCAATCGTAATTACTCT GTAGC

CATTTCCTGTCCAATTTTGTGGCAATGGCCATTGTACTATTTGGGTGAATCTGTAAG CGACC

GTGCTTTCAGTTCTTCATGTCCAGTGGTTGTAGGGGTCAAGTCCTTGTACATATTTC TTTTAC

AAGTGCAGTGGAGTAGGAGGTCAAATTGGCAATATTCTTTGGCATTTCCTTCAGGGT GATGC

TGAAAGGTGGAGGACGACCAATGAATGCTCTATGCACACGCATTGGGCACTATTTTA GGGT

CCCCAACTGACATGATTTTAAATTGAAGTTATTGTTAAGTAATGACTCTTTTAATGA GTCTTTT

TGCCATGTCACTTCAATAAGCTTTTGAAGTGAATTCTACATGGATAATTTTAGTTGT TTTTATT

AAGAAGGTTTGACTTACACTTACTAAAAAAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

164 CCAAATAGCACCATCTGAAAATGCTCGGACACAGTAAATTAAATTCACTCGAGAATAAGT TC

CTCGCCATTCACAATAAATGCGCAGAGCATTGCCATCCATGCTCTTCATCTACTTCC GTCCT

GGCTATCCTATCATGCCAAATTTGCAGATAGGTTTTAGGGTACCTCCAAATGGGTTC AAGCA

GTCATCGGGAAAATGGAGCAGTGAAGGCGGTCAGCTGTTCCAAAGAGGATAAATTAG AGCA

AAGCAGAGTGAATTTGATGAGAAGTATTGTTGAAGCTAAGGACTCATCTGCAAAGGC TACAG

ATGATGCTACTCTCAGACGTTTTCTGCGTGCACGAGATTTGAATGTGGGAAAAGCTT CTGAG

CTTTTCTTGAAATATCTAAAGTGGAAGCGAGCATTTGTGCCCCTTGGCTATATTCCA GAGTCA

GAGGTCTCCAATGAACTCAGGAAGAATAAGATTTTTATTCAAGGACTGGACAAACAA AGGCG

CCCCATTGGAGTGATTCTCGCTGCAAGGCATAATGCCTTTGACAGGGATCTAGAGGA GTTC

AAACGGCTAGTTGTCTATGGTTTTGACAAAATATGTGCCTGTATGCCAAGAGGACAG GAAAA

GTTCGTCATGTTAGCAGATCTCGAGGGTTGGGGGTATAAGAATGTAGATATCCGTGC CTAC

CTTATGGTACTTGAAATTATGCAGGATTGTTATCCGGAGCGGCTGGGAAAGTTATTT ATGATT

CACGTCCCATACCTATTCTGGGCAGCATGGAAGACGGTTTATCCGTTCATTGACAAA GTGAC

CAAGAAAAAGATTGTTTTTGTTGAAGATAAACACCTTAAAGAAACATTATTGAATGA TATTGAT

GAAAGTCAACTTCCAGAAATTTTTGGAGGGAAATTGCCTTTAGTACCTACTCAAGAT TGTGTC

ATACCCAACTAACACTAGATACCTTGAGTTAGGAATGTGGAAGGTTTTAATAGCAAT GGTTAC

CAAAAAGTAGATTAGCTTTTCTTTAGACATATATTGCAAATCCTATTATCTTTCCAT TTTTTTTT

ACCTTTTTCATATGTATAAATATTGGTTTTGAAAACATTGAGAATGGTCAATGTTTT GACATTT

ATAACAAATTTATTAATAATTTAAAAAAAAAA

165 CAGGGGTTGAAAATTATCTCGGTAAAAATTAGGGTTTTGTTTGATGAGAGGGCGCGAGAG G

CCAGTTGATTAGATTGCCCCATCAGATTCCCACGTCCGACTCTCTGGCCGATGACAG AGCTT

CCATTTAAATAATTCTGCTCATTACCGTGTCGCTATTGAAGTAAGAGAACCCAAAGG CTCTGA

CGATGCTCTTGATTCCCTCTGTGGACGCGCTTTAGATTTGTTCATTTCTTCTAAAAT GGAGAA

CGTTGGCGGTGAGGAGTACCTGTTCAAGATCGTGGTTATCGGGGACTCTGCGGTGGG TAAA

TCGAATTTGCTGTCAAGGTATGCTCGCAACGAATTCAACGCCAATTCCAAGGCAACG ATAGG

CGTAGAATTCCAGACCCAGGTGATGGATATCGATGGGAAGGAGGTCAAGGCTCAAAT CTGG

GACACAGCAGGCCAGGAGAGGTTCCGGGCGGTCACATCGGCATACTACAGGGGAGCT GTG

GGAGCCCTCATTGTGTATGATATCAGTCGCAGGCTTACTTTTGATAATGTCGCCCGC TGGCT

CGAAGAGCTCAAGATGCATGCTGATGGCAATGTCGTGAAAATGCTTGTGGGGAATAA GTCT

GATTTAGCTCATATCAGGGAAGTTCCTGTGGAAGATGGGAAGAAGCTTGCCGAATCA GAGG

GGCTGTTCTTCATTGAGACCTCGGCTCTGGATAATACAAATGTATTGCCTGCATTCC AAATT

GTGGTCAAGGAGATTTACACTAATGTGAGCAAGAAAATGCTGAATTCGGATTCCTAT AAGTC

TCAATTGTCTCTCAACAGAGTTAATATTACGGATGCATATGGAGATGGAGATGGAGT GGATC

CACCCAAGACAAAGAATTCTTGCTGCTGAGGATTCAGAGAGAATGCTCCTTTGTTTC TGGGC

TCCTTGAATATTATTTGCTTCATATGACCTCTTGTTGATTGAGATCCTTAAGGCTGC CTTATG

CTAATTTAATTTTTTTTTGTTTATTAGGAAAGTTTCAATATGTTGGATAATTTTTTT TCAATTTTA

TGAAGAAACCAGTAAGGGTCCCCAACTGGGCTTCTTAGGCTTGAGCCCTAGATGCT

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

166 GATTGGAATTCATGAGACGAAAATTACGGTACAGATGAATGGCTGGAAATAATGAATCCC AA

TAAAATGAGACCTTGAGATTCACCCAAGAGAGTATGGCCTTTCCTGGTCTGGTTTTG GTAAA

GGGCAGAGTCGTATAAAGAAGGCGGAAGGGAGGAGGGCAGAGTCGTATAAAGAAGGC GGA

AGGAAGGAGGGCAAGTGAGAATTCCCTAGCAAAATCGCGTGGACAAATGGTCAATTC GTAT

ATGTGGAATGCACCCAGCCAGGAATTTCGTTGCGGGCAGAGGGCAAAGACAAGGGTT ATG

GCTTTTTTCGAAATTCATTCGGTTCAAATTTGACCTGAATACGGTTTCTAACAGGTT AGAATA

TACGATTCTAGACGCTTTTACTTGGTCGCTGCACGCAGTCCTAATTGTTGTTTTCCT GTTCTT

GTGGTTTTCCAACATTTTTAGGATCATATACCGGAGTACCCTTACATGAATTTTAGC TCCAGA

GGTTCGGATTTGGGTTGATGCCGCGAGGCTTGTGATCTGTGATACATTGTCGTCGTT TGAC

CCAAGAATCGACCCAAATCCATTCTTTATATGTAATATGCAGGAAAGGTCCGAGGAG TAAGG

ATTCCCAGCCTAGAACCCAAAAAATAAGGTCCAAGGTCGAAGTCAGAGGCTTGTGCT ACATC

CCAGTGTTTTTTGGGATTCTGTCGAGTCCTCAAGAGGGCTTTTTGCTTTACGGAGTA CCCAT

CTGGAATTAGTGAGTTCAGTTGCCTGCCTAAGAGTTCCCGCATAGGGCAAGGATTTG TTTGA

GATTGAAAAAGGAGGGCTTTTGCAATGGGGCATGCGGCATCTGTGGTCATTCCCCCA CAAG

AAACAAAACAAGAGGATGAGGATTCCCAAGAAGGCGTAGACTACACCCTGAACATTC CTGAT

GAATGTCTGGCACACGTTTTCCATTACCTGAAGCCTGGTGATAGGAAGCCCTGCTCT TTGGT

GTGTAAGAGGTGGCATCACGCGGAAGGGCAGAGTCGGCGTCGGCTGTCTCTTGATGC ACG

GGCGGAGATTGTGCCGGCCATTCCTAGTTTGTTTTGGCGCTTTAATTATGTTTCCAG GCTCG

CACTCCGAGGCAATCGGAGGACGATTGGTATCAACGATGACGGACTGCTTCTGATCG GCAT

TCATTGCAAGAACTTGAAAAATCTCAAATTGAGATCCTGCAGAGAGATAACGGACAT TGGAA

TGAGTAGGTTCGCACAGTTGTGTGGTTCCTTGAGGAAGTTTTCTTGTGGGTCATGTA CATTT

GGTACTCCGGGGATCAATGCTATCACGACCCATTGCAAATCTTTGGAAGAGCTCACT GTAAA

ACGGTTGCGAAGCGCAGGGGAGGTCCCTTCTGAACCAGTTGGACCTGGAGCGGGGAA TCT

GAAGAGGATTTGTTTGAAGGAATTATACTACGGACAGTTCTTTGTCCCACTGATTGC AGGGT

CAAAAAAATTACAAACTCTTAAGCTTTCTAAATGTTCTGGGGACTGGGATACTCTTT TGGATA

TCATCACTCAGGATGTCACAAGCCTTGTTGAGGTTCTTTTGGAAAGATTGCATGTGA GCGAC

ACGGGTTTGCTAGCAGTTTCAAAATTGGCAAGCCTGGAAATTTTGCATTTGGCTAAG ACGCC

AGAATGCTCTAATACTGGGCTTGCAGCTATTGCAAATGGTTGTAGAAAACTGCGAAA ATTGC

ATGTAGACGGATGGAGAACAAATAGGATTGGTGATGAGGGTCTTATTGAGATAGCTA GAAA

GTGTCATTATCTGAAGGAGTTAGTATTGATTGGAGTCAATCCCACTATAACAAGCTT AAGTAT

GTTGGCTTCCAATTGCCATGTATTGGAGAGATTGGCTCTCTGTGGCAGTGCGACTAT TGGTG

ATGCGGAGCTTTCTTGTATAGCAGCCAAGTGTTATTCACTAAAGAAGCTGTGCATTA AGGGC

TGCCCAGTCTCTGATCAAGGCATGGAATCTTTAATAAGTGGATGCCCCATGCTCGTG AAGGT

GAAAGTAAAGAGATGCAGAGGTGTAACCAGTGAGGGTGCGGACTTGTTGAGAGCTAA TAAA

GGTTCCCTGGATGTAAGTTTGGATACTATAACCTCACCTAGTCTGAATGGGTTATCA ACTCA

AGCCAGCTCGAGTGTGCCAAGAGCATCTGCCATTTCTTCAGCTGGTAAATCAACTCT ATCTA

AGGCAAGATTGACCCTTATAGCAGGTGGAAGCTTTCTTGCCTGTGCCTTTTTAAAGT TGTCA

AATGGCTCATAAGTGAACCTCTMGGCTCATTATGCGGAGGTCTAATTGACCAGTATT GTTG

AATAAAGAATACTGCATTTGCTGTTTATCTTATCAAACCATTTACTGATGGATATCT GAGGTAT

TGATGTTGTACGATCCTCAGATCTACCTTTGATGCGTTATGCTGATTATTCATTTGG TACATT

CTGAGATTGCGCATGGGTTTCTGAATTGGCAGAAGCAAACTGGGTTGAATCAATACA GCTAA

TTTTCTTTTTTTGAAATTAATGTTTTTTGGGATTGGATTTGACCAAAAAAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

167 TGGCTATGCAGCGCTCCAGCGGAGCCTGCTTTGATGCAGCCATTCCTTCAACAGCTCTGT T

CTTTGGTTGTTCAGAAATTCCTTGATGAAGTCTGCTCCGTTCCAACCTCATGGTTTG GCAGT

GGTCCAAATTATTTACAGGTTGTTGGGTTCGGTTTTAGCCCGACTTACTTGGTGGGG GCGAC

GCATCTACAGCGACGGACTTCACCGGTTACGGTCTTGAAGGATTCAAGAAATTCGAG TTGC

ATGAAAGAATGGCCGGCTTAGATAATGGGGTAGTTAATGGTATCGTGTCTGTGAAAT TCACC

AAACTCTTTATTGATGGAAAATTTGTGGACGCAATTTCAGGGAAGACTTTTGAAACT TTGGAT

CCTCGAACAGGAGATTTGATAACGCGCGTCGCAGAAGGTGATAAGGAGGATGTGGAT TTGG

CTGTGAAGACGGCCCGGGAGGCTTTCGATAAGGGACCTTGGCCTCGAATGTCTGGCT ATGA

AAGGGGTCGCTTACTGAATAGGTACGCTGATTTGGTAGAGCAGTATATAGATGAACT AGCAG

CTCTTGAAACACTAGATAATGGACAACCACTCACCCTTGTCCGTGTCATTGTGACGG GGTGT

ATCCAGATTCTCAGATACTATGCAGGAGCGGCTGATAAAATACATGGGGAAACATTA AAAAT

GGGAGGGCAATATCAGGCATATACTTTGCATGAGCCTATTGGAGTGGTCGGTCAGAT TATA

CCATGGAACTTCCCACTTTTCATGTTTTTCATGAAAATCTCTCCAGCTTTGGCTTGT GGATGC

ACTATAGTTATCAAACCTGCAGAACAAACTCCTCTAACTGCACTTTATTGTGCACAT CTGGCC

AAGGAGGCAGGGCTTCCACCTGGTGTTCTTAATGTGATAACTGGTTTTGGAGAAACG GCTG

GTGCTGCAATAAGCAACCATATGGATATTGACAAGGTAGCCTTTACAGGGTCTACTG ATATA

GGTCGGGTTATCATGGTGGCCGCTGCCCACAGCAACTTGAAACCTGTAACCCTTGAA CTCG

GGGGAAAATCTCCGTTGATTATCATGGATGACGCTGATATTGAGGAGGCCGTGAATC TTGC

CCACAAGGCCATATTTTTTGGCAGTGGACAAGTATGCTGCGCAGGATCCCGGATATA TGTTC

AAGAGGGCATCCATGATAAATTTGTGAAGAGAGTAGTGGAAAGAGCGAAGAAACAGG TGGT

CGGCGATCCTTTCAACCCAGAAGTTGACCATGGTCCTCAGATTGACAAGACACAATT TGAAA

AAATATTAGAATACATTGAGCATGGGAAGCGAGAAGGAGCAAAACTATTGACAGGCG GTAG

TCGCGTGGGTGAAAAAGGATTTTACATTGAACCAACCATTTTCTCCCATGTGCAGGA GGACA

TGAAGATTGGGAAAGAAGAAATATTTGGACCAGTCGTGTCCATTTTCAAGTTCAGGA CCATT

GAAGAAGCCATAGAACTGGGCAATAAAACAATATATGGTTTAGCTGCTGGAATTGTG TCGAA

GAATATAGATACAGTCAATAGGCTTTCGAGATCTATTCGAGCAGGAGTGATTTGGGT TAACT

GCTACCACGTAGTATTTCCTGATGCTCCGTTTGGAGGGTACAAGATGAGTGGGATCG GTAG

AGAGCAGGGTCTCGATGTTCTTAAAAATTATTTGGCAGTCAAGTGTGTCATAACTCC TCTCC

ATGATTCACCTTGGTTGTAGAACTATGCTTTAACCTCTTTCAAATGTGTTTGTCAAA TGCTTTC

ATAGCTTTATATATTTAGGTTGAAGCTTCAATAAATCTTTGTATGTAAAAAAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

168 CAATTTCGTCGCAAGTCGATGGAGACCGACAGTCCTCTGGTCGCAATTTCGTTTCAGCCG C

CGCCGGTTGCATTTATTGGGCAAGAATTTGATAATTTTTTATTTTTGAAATTGGACG AATTTC

CGTGCATTTCATTTCATTTCAGGTCTGAACAGTCAGACCAGCGAGCTCTACAAAAGC TTCAG

GTACTGTGAGGGAAAGGGCAGCTCGGCGCACCAAAGAGCGGCGAAATAATGGTGAGG AAT

TTGCATTGGTGCAGAGCAATTGTTACTATCAGCTCGGCCGTTCTTTTATGTACATTT TGAGCC

GTTTTACGATCAATTTCGCCAGCTCTTACGATCAATCCGCTGAGCAGTCTAGTTTAG AATCG

GGGCGCCATGAGAAAGAAGGATCTTAAGAAGTTGAAGCTCGCGGTTCCCGCACCGGA AAC

CCCTATGTCTGACTTCTTGACTGCAAGTGGTACATTTCAGGATGGTGATCTCCTTCT AAATAG

GCAAGGTTTACGGCTTATTTCCCAAGAAGATGATGAGAGTCCATCTCCAATAGAGCC ACTTG

ATAACCAGTTTACTCTGGCTGACCTAGAGACTGTGAGTGTCATTGGAAAAGGAAGTG GTGGT

GTTGTTCAACTGGTTCGTCATAAATGGACAGGGCAATTTTTTGCTTTAAAGGCCATT CAAATG

AGCATTCAAGAGAGTGTTCGTAAACAAATTGTGCAAGAGTTGAAAATAAATCAAGCT TCACA

GTGCCCAAATGTTGTAGTTTGTTACCATGCTTTCTATAACAATGGTGTTATCTCTAT AGTTTTG

GAGTACATGGATTGTGGCTCTCTTGCAGATGTGATAAAAAGAGTCAAAACATTTACA GAGCC

TTATCTTGCAGTTATTTGCAAGCAGGTTCTCAAGGGATTGATATACTTGCATCGGGA TAGAC

ATATCATCCATAGAGATATCAAACCATCAAACTTGCTAGTCAATCACAAAGGTGAAG TGAAGA

TCACAGACTTTGGTGTTAGTGCAACGCTAGCAAATTCAATGGGCCAACGCGATACCT TCGTT

GGTACCTACAACTATATGTCGCCAGAGCGGATAAGTGGAAGCACATATGGATTTAGC AGTG

ATATTTGGAGCTTGGGCCTGGTTGTGTTGGAGTGTGCTACTGGTCGTTTCACATACT TACCT

CCTGGACAAGAAGAAGGGTGGCTCAATTTTTATGAGCTTCTGGAGACAATTGTTGAG CAACC

AGCACCTTGTGCATCGCCAGATGAGTTTTCACCAGAATTTTGCTCCTTCATCTCTGC ATGTG

TTCAAAAGGATCCGAAAGACAGAATGTCGGCCACAGATCTTTTGAATCATGCCTTTA TCAGG

AAATATGAAGACCAAAATGTTGATCTCGCAGCTTTGCTCAGCAGCTTGTCATCACCT GTGTA

ATCATAATAGACATTCAAGTGATGACACCCTATGGTAAAACAATGGTTTCCAGATTC CATGAT

TGGAATTTAGTTCTGTATAAGTCATAGCTTATCTCAAACTACGTAAATGAGTAAAAC CAAATG

GGCATTAATATATGCTAGAATTAAGCTGTTGATGTAGTATTGCTTAACTGGCAATGG GGAGT

GAATCTCCACTCAATTATGTGATGTCCTTTATTTAAGAAACCCTAATCATAAAACAT CTGTCGT

GCTCTATTTAGTCTAAAAAAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

169 TAGGAGCCGGCTCTGGTTAGTGCTACTGGAGAAGAGGCAGGGAAAGGGGCAAGGGCAGG

GGTAGGAGCAGGAGAATTGCTTAGATTGAATATGGCGCTGATGATGGAGTTTGGGGA TGAT

GCTGGTATTGGTGAGGAGTGGGAGGATAATGAGAGCCAGAGAATGGAAATTGACACG GGG

AAGGGAATAGAAACCCATTTCAATGACATCCCAGAGGTGATAATGAGCAACATATTC AGCGC

CATCAAGGACACTCGATCGCGGAACCGGATGGCTCTTGTCTGCAGGAAGTGGCATGA AATG

GAGAGGGCGACTCGCGTGTATCTGTGCATAAGAGGTAACATAAGCAACAACTTGTAC CGGC

TGCCCATGTGCTTTCAGTCTGTTACTAAATTGGATCTCTCGCTTTGCTCCCCCTGGG GTTAT

CCCCCTCTGGATTTCACCACTCCGCACGGTAACTTCATAGGGCATCGGCTCAAACAG GCAT

TCCCCAGAGTGAACAACATAGTGATCTATGTAAGAAGTGCGAGGAATATAGAGAAGT TGTCC

TCTCTGTGGCCTTGTCTTGAGCATGTGAAATTGGTGAGATGGCACAGGCGTGCCATG GATC

CTGAGTCTGCAGTCGGTTTGGGAATGGAGCTTAAGCTCCTGATGCAAAATTGCACAG CGTT

GAAGAGCCTAGATCTCTCTCAGTTCTATTGTTGGACCGAGGACATACCGCTTGCCTT GCAG

GCCGAGCCACATGTGTCGGCCAATTTGTCAAGCCTCAACTTGCTAAAGCTTTCCGCG GAGG

GTTTCAGGGCCCAGGAGCTTGCAGCCATATCAGGGGCATGTAGGAACCTTGAGGAGT TGCT

TGCCGTTTGTGTTTTTGATCCAAGATACATGGATTGTGTTGGGGATGAGGCTCTTGT TGTAC

TTGCCAGAAACTGTTCTAGGGTCAGAATTCTTCATTTGGTCGATGCCACTGCATTTG AAGCT

CTCAGAGGCGATCCGGAAGATATTTTCTCCAGCGAGAATGCCAAGATTACCCGCCAA GGTC

TGGAAAGCATGTTCTGGAATCTACCTCTTTTAGAGGATCTTGTGCTGGATATCTCTC ACAATG

TCGCAGACTCGGGCCCCGCTTTGGAATTCCTAAGCTCCCATTGCAAGAACATCAAGT CTCT

GAAGTTGGGTCAGTTTCAAGGCATATGCAAGGGCCCTGAACCCGATGGTGTTGCCTT GTGT

ACAAATTTGGAAGCTCTCTTTATAAAAAACTGTTCTGATTTAACTGACACGGGCCTC GCAGC

CATTGCAGCTGGGTGCAGTCGTTTGGGTAAATTAGAGTTACAGGGATGTAGGCAGAT CACC

GAGGCTGGTCTCAAGTTTTGTACTAGTCGACTTAGTAAAACTCTTGTAGAGGTCAGG GTTTC

ATGTTGTAAATATCTTGATACTGCTGCCACTTTAAGAGCCCTTGAACCAATATGCGA GAGCG

TGAGAAAGCTGCATATTGATTGCATTTGGGATAAGTCCATTCTTGATCAAGAAATTG CTTCTC

CTAGTCGGAGGTTGAATCCAGTTGGATCTTCTGCCATTTCCACAAGGGAAATAGCTA GCTAT

GGAATGGGAAAAAACCATCTAGTTTCTGCTGGAGATTGCAATGTCAACAGATGGGAC CAGA

ATCCGGAGAGTGCTTGGGGGCCATCCTTGCAGTTGGCTCCTCCTCAGTTTTGCCCTG ACCT

CAACTGCGCAAATTTCGATTTTGGTTCAAGCCCTTCGGATGTACCGATGACAAATTG GGGCC

TGGATCTTAACCTGACTGCAAGCTCATGCTCAGGGCCTTTAGAAAGTTCCGAGGAAA GAGG

CTGTTTGCCTATAGAAAATTTCTTCGAAGAACATGAAAAACCGAATTCCCTTGGTTC TGACAG

GTACGTGCCTTCCGATGGTGTCATGTTTAGAGGCATGGATGTGAACGGAAAAGCTCC ACAG

ATGGAGCGACTGTGTCATTCCAATACCGGCACAGTTTCGGATTCGTCATCCACAGAA TTTGT

GGACTTTTTGGGGATAAATGACAAGCATCAAGAATGGCAGAAACTTGGAGCAGATAT TAATT

ATGGTATGGAAGTGATGGTCAATTCATCTCAAATATGGGGTGTAACAGGGGAGGCTA GTAAA

AGAACCTCCTCAGCAAACTTAGAAGGTGAGCAGTCATGGACAGAGATCCCCAATCAA TACA

GTTATAGTGATTCGAGCAGTCATATCAQATCTATAACTTGGAAAAATCTGCAATTCT TGTCAT

TGTGGATTCCCGTAGGAGAGCTGTTGTCACCTCTTGCAGCAATGGGTTTAAAAGTAT GCCC

GCTGCTTGAAGAGATTAGTATCCAAGTAGAAGGGGATTGTAGGCTCTGCCCCAAACC AAGA

GAGCGTGCATGTGGTTTAAGTTCACTGGCATGCTATCCTTCTTTGTCAAAGCTCGAG CTCAA

TTGTGGTGAGGTGATAGGTTTTGCATTGAGCGCACCTGCTGGCAAGATGGATTTGAG CCTG

TGGGAACGATGGTACCTCAATGGTCTTCGAGAACTACATCTGTCAGAACTGAATTAC TGGCC

TCCACAGGACAAGGATATGAATCGGAGAGGGCTTTCACTTCCAGCTGCAGGTCTTCT TTCA

GAGTGTGCAGCTCTTCGGAAACTCTTTGTTCATGGAACTTGTCATGAACATTTCATG ATGAT

GTTTATTCGCATTCCAGACTTAAGAGATATACAGTTGCGGGAGGATTATTATCCAGC CCATG

AAGATGATACAAGCACTGAGATGCGTACTGATTCATGCAGGCGTTTCGAGGAAGCTC TAGC

TAGTCGCGGATTTACTGACTGAATTAGGTTTTGTGAAACAGGGTTTATTGTTGATTG ATCTTT

CCAAGGTCAACTGTGGAGTTTCAGAGGAAGTAGTATTGTATGATCCTCGTGAAATAA CATCC

TGAAGGTAGAGCCTGCTTGTGGTGTGCACGACTTGCAAGACAATAACCAGAAATTTG TATGT

CAAAGCATCAGAAGACATACAAAAGGATCACTGCCTTTCGGTGTCAGGGGTCTCAGC CATG

GATTTTAATATTAATTGTGTCAGTGAAAACTTCTGCCTTGATATTTGGTTCGAGTAA TTGGAG

ATAAAGACTGATTCTTCTTTTAAAACCATTTGGCTGAAGACTCTGAAATAAAGTATA GAATATT

ACAGTATGTCCACTCACTCTTCCAGGGTTTCCCCGATGGATTTATGTTCAGGTGCAG CATTC

CTCGTCTAATGTGTCAGTGGTTATACTTCCTTTGGAATGTATCTTTCATGAGACTCA CTGTTC

TTTTGGTGAAGGGGAATCATATGTCAATCACAATAGGCTGCTGAGGACACAGTAGAA CCTAG

ATTATTTAGTGTAGATGTACCCATTGTATCAATGTCAAATGTCTAATACTCATTTGA TTTTATT

GACTGGCCCATACTTGTAACCGGTTCCTTGTTTCAACTGTTGCTCTTTTGTCCACGG TTGAA

AATGTAATTGATGGGAGAAATAACAACATAATAGAAATACTTGCCTCCAAAAAAAAA A

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

170 AGGAGATCGGAATACCACTCAGGTTAACCACATTAGGTAAATTATTTTATGTTTTTAATT GTG

AAGGCAGTTAACTTGTCATCTTGTTGTTTGTCCCAGTTAATCATCGTGGGGCTGAAC GATTT

CAGGGCCATGGTTTTCATTTCCATTCTTTCCACCCCATATTTTTCCTGGTTTCTGAA CTCAGA

ATGACTTGATTTCCCCATTAGCGTGGAGTCCTAGGTTGCACACATCCTCAAACTCTC ATTCT

CAACTACGCATTTGTTTAAGACCCTCACTTCCCAAACCCCAATTTGGGTTTCTTTTC AATATTT

CCCCTGCGATCGAGTACATTGGAGATCAGTGAGTGACGGGCAGCACAGGGGCCGAAA GGA

CAATTTTCCTGCTTTTTCTTGTTTTTCTGGCAATGCAGATATCAGGCACTCGCAGGC CTTGCA

GGCCATGGGCTTGTGTTGGTTCTCTATGACTGAGCGCAGGAGAATAGATCTAGAATT GTTTA

TTAATGGGAGGATCAAGATAAACAGTGGGTTTTTTATCAGAAGCAGAGGCAGATGGG GCAA

ATGTGGTTGACGTACAGACCAAGCTGAGAAAAGGCTGATTTTTTCCTCTCATTTGAA GCGCT

CCCCATGTGAAAAGATTTGGTATTTGTGGTTCCAGGCAGATTCGCAGATAGTTGAGG CATTG

GCCTTGTATCAGGACATAAGAATACAGCGTGGATCTAAAAGTGAACGGAGACAAAGA ACTAT

GCAGCAAGATCAGAGAAGAAAAGCCCCTACAGAGGTTGAGTTTTTCACTGAATATGG TGAA

GCAAGTCGCTACAAGATTCAGGAGGTTATAGGAAAAGGGAGCTACGGTGTTGTATGC TCTG

CAATTGATACTCACACTGGGGAGAAAGTTGCAATAAAAAAAATAAATGATATCTTTG AACATA

TTTCTGATGCAACCCGGATTTTACGTGAAATTAAGCTTCTGAGGCTGCTGCGGCATC CTGAT

ATTGTCGAAATCAAGCACATTATGTTACCGCCCTCTAGGCGGGAATTCAAAGACATT TATGT

GGTATTTGAACTTATGGAATCAGATCTACACCAGGTTATTAAGGCAAATGATGACTT GACAC

CAGAACATTATCAATTTTTCTTGTACCAGCTTCTACGAGCTTTGAAGTACATACATA CTGCAA

ATGTGTATCATCGGGATTTGAAACCGAAGAATGTTTTGGCAAATGCTGATTGCAAGC TAAAA

ATATGTGACTTTGGCTTAGCAAGAGTTGCCTTCAATGACATGCCGACAACAATCTTC TGGAC

GGATTATGTTGCCACAAGATGGTATAGGGCTCCAGAGCTGTGTGGATCCTTTTTCTC CAAGT

ATACACCTGCCATTGATATCTGGAGCATTGGTTGCATCTTTGCCGAAATTTTGACTG GGAAG

CCCCTTTTCCCTGGTAAAAATGTAGTTCATCAGTTGGATTTGATTACCGATCTTTTT GGAACT

CCTCCCATCGAAGCCATTTCTCGGGTTCGCAATGAAAAAGCTAGAAGATACTTGAGC AGTAT

GCGCAAAAAACAACCTGTACCCTTGTCCCAGAAGTTTTCAACTGCAGACCCATTAGC GCTTA

AACTTTTGGAAAGATTGTTATCTTTTGACCCAAAGGATCGTCCAACAGCAGAAGAGG CTTTG

GCTGATCCTTATTTCAAAGGGTTAGCAAAAGTGGAGCGAGAACCTTCAGCTCAACAA ATAAG

TAAGATGGAGTTTGAGTTTGAGAGGCGAAGGGTAACAAAAGAAGATGTGCGGGMCTC ATT

TTTCGGGAAATACTCGAATATCATCCGCAGATGCTAAAAGAGTACCTAAATGGATCA GATAG

ATCCAATTTTATGTACCCTAGTGCTGTTGATCAATTTAAGAAACAGTTTTCTCACCT TGAGGA

ACATTATGGTAAAGGTGCACCTGTGGTTCCTTTAGAAAGGCAGCATGCATCTTTGCC AAGAT

CATCTGTTGTTCATTCGAACACTATGCCCCCCTTGCCAGAGAAAACAATATCAGGTC CTTCA

AGGGACCGTACTTCAGAATCCCGTGATGAATCTTCTAGGTATATTAGGGAAACAGAG AAGCT

GCAGCATGATAGGAGTGCAGGAAATGCACTGAAGGCTCCCTTGCAACCACCTCAGAA AATC

TTGCAGGGGGGTGCTGCAAAACCAGGGAAAGTTGTTGGACCTTTGCCTTATGAAAAT GGTA

GTACGAAAGAAGTCTATGATCCAAGAAGGTTGATCAGAAATGCTGTTCTAACAACGT CTCAG

TATGCCGCTCCTATTTACTCATATCCAAGAAGAACTTCAAACACAAAAATTGAACCG AATGAA

AAGGAAGACGCTGAGTCAACTTTAATGCCACCCAAGGCCCAATATGTTGGAATTGGT GCAG

CAAGGAAAGTAGCTGCAGTTCAGAGTGCTTCCTCTCGCTTATATTAAGCAAAATCAA TTTCCT

GGTAATTGCAATTTGTAGCCCATTTAGACATTGTTGACTGACATCATTCTTTATTAC TTGGCA

TCTTCCAACACTGAAGCAAATTGAGCAACATATCATATCTAGCATGTGAAGAAGATG CTCAT

GTACAAAAGGTTTTCCCTTTTCATGATGACTGAATATGGTTCAGTATCAAGCCCAAA AGGGA

CAACAACCATGCAGTCCCTCTGTACTGTAAGAAGAGATGAACTCGATGAAATTAGTA TTTTAT

GGAAAATGTAAATGATTTGACTGTAAAAAAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

171 ATCTCTGCTGCTCTGTGTTGGGGATTTTGTCTCGATGGCGCAGCAGGAACAACAGTAGTA G

CAGCAGCAGCAGCGGCTGCTTTCAGAGATAAGGAGATCCGCATAGATTTTTTAGTGT CGAG

TTAAAATATCTGAATTTCAGTACACACATGCGCGCGTATGCACATGGGGMTTCGGAA GCAT

CCGCCAATTATGACCACTTACGCGTCCCTCAGTTGGTCCTCTAAGCTATTGCTACAG GGGGT

TCAGACGTCTGGAGCACAGTACACTAGAGGATCCCGTTTAGCAGACTAAATCTCAAC AGAAT

TTTGCCTGCTTTTCTCCCTATATAACCTCCTCTCTCTCACCGGCTTCGGTTCTGATT TTTCCC

GCAATGGGGCCTTGCAATGGCCGTTTCTCAGCTCTGATTTTGATTTCCATGACTCCG CCTCC

TTCTCGTGTCGGCGTCCTGATCTCGCTCTTTATAATGTCTCTGTTACTGTGTATTTC GGCGC

CCTGCATGCACAGCCCTGCGGCTGCCCTGATCGGCTTGAGTCGCTCTGAGAAATACA ACAC

AGACGGGCAAGATCCGTGCCGTCTATCGTTCCTGGACACGGCGGCGGCTGCCATCGA CTT

CGGCAGGATTTACCATCACAATCCCGCGGCTATCCTCCGGCCGGTGTCCGCTGAAGA AATA

GCCCGTTTTCTTCGGGCTATTTATGCGTCGAGGGCGCTCGCGACCGGCTATCGCCAG GAAT

ACCTCACCGTTGCTGCCAAAGGCGCCGGTCACTCCATCCATGGCCAGGCGCAGGCCC CCG

ATGGGCTCGTTATTGAGATGTCTTCTCTCAGAGGCGTGCGCATTCATGTGGCGGACC GCGC

CGGCGGCTACTCGTACGCCGACGTTGCTGCCGGAGAGCTCTGGGTGGACTTGCTCGC AGA

GGCGATGAAGCTCGGCCTCGCGCCTCGATCGTGGACGGATTACTTGTATCTCAGCGT CGG

CGGGACTCTGTCGAATGCAGGTATCAGCGGGCAGACATTTCGCCACGGGCCTCAGAT CAG

CAACGTCCTGCAACTTGACATAATCACAGGGACCGGAGAATTAGTCACTTGCTCTCC TGCTG

AGAATGCGGATTTGTTCTACGCTTCAATGGGAGGCCTTGGCCAGTTCGGCATCATAA CCCG

AGCTCGGATTATCCTCGAACCAGCTCCTCAGAAAGTGAAATGGGTTAGAGCCTTATA CAGTG

ATTTCGAGCAGTTCACAAGGGACCAAGAGCTCCTGGTGTCCATGGACGATGGCGCCG CATC

TGTAGATTACTTAGAAGGCTTCGTGGTCGTTAACAACGAGGCAATGCGCAGCTGGTC GATC

TCGTTCCGCACTGACACACCGCTCGATGACAGCGTCTTCAACGACGCTGGAACCGAG ATTC

TGTTTTGTATTGAGATAGCMAGTACTTTACACMTCCGACGACGAGACAGCCGATGTC GAC

AAGGTCACGGGGCGGATTATCTCGAGATTGAGTTTCATTCCTGGGTTGATTTACAGT GTGGA

GGTACCCTACGCCGATTTCCTGAAGCGAGTACGAGTGGAGGAGCTGAACCTGCGATC TCGA

GGCCTCTGGGACGTTCCGCATCCATGGTTGAACATGTTCGTCCCACGGCGCCAAATT CAAC

GTTTCACCACTTCTCTGCTCAGGATCATGTCTCCGGACACTGTCAAGGGCCCGATAC TCGTC

TACCCTGTGAAAAGAAGCAAGTGGAATACCAACATGTCTGCAGTAATACCTGAGGAC AAAGA

CGAGATCTTTTACGCAGTGGGCGTTCTTCGATCCGCAGACCCACTGTGCTTGGCCGG GTCT

TCCTGCTTAAACGATTTGCTATCACAGAACCAGCAAATAATCGATGTATCGACAAAC GCAAA

CGAGATTGGCAACGATAAGACCGAACCAGGCATGGGCGCGAAGCAATACTTAGCCCA CCAT

TCCCAGCAATGGCAGTGGAAGAATCATTTTGGGAGCAAATGGGGAATATTTCTGCAG AGAA

AGGCGAGATACGATCCTCTGAACATTCTCGCTCCAGGACAAAGGATTCTCAATAGAA ACCAC

CGAGAATGACCTGACCATGATGATCTGTCCAAGGAAACCAGAGATCTCGCTAACAGC AAGG

CCAGTAGTATAATGAATACAGTAGAATATTATATTTTTATTTCTGTCCTCCCTGTAA GATCCCT

GGCACATAATTACAATAAMTTTATACTGMCTAMCTTTTTGGCATTACCCCAAGGTTT TCTC

CATACTTTGGTCCATTTATTAGGCCAGCTCACAGTGTGGGTACMGCCAGTCTGCAAT TGCA

GTTCAGCAGATGCATCATCACCTGTAMAACAGTTTCACCGATTTTTTTTTACAGTGT AGAGC

ATCTTCAGGCACMGGACTACAGTATTACGGCGGATGATCAGTATAGCTGCTGAGCTG AMT

TCGCGGATGATTTGTACAGGAGMTTMTGTMTACAAAAGGATATTTTTACTAAAMMMA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

172 GTTGTTTGTTGTTTGATTCTTCTGAGAGTAGGCCCTGCGTGTTCTGAGACTTTTTTGTCG TTT

TAATTTCTATTGAACTTGGCTCGTCATTTGTTCATTTTCAAGTATTGATTTGATGTA TAGGAGG

TGACAACTTCTGTAAGTTTTTAGATGGATCAGGACCAATCCATCTGCAGATTTGCAG CTCAG

AAGGGAAAAGGAGAGATTCAGTCTTCTTCATTCCCAGACGAAGTTTTGGAACATGTT TTGGT

TTTCCTGTCCTCCCAGAAGGACAGAAATTCTGTTTCCTTGGTATGCAAGGCCTGGCA CAGG

GTTGAGGCGTGGACGCGCCAGCAGGTGTTCATTGGCAACTGTTATGCTGTCTCCCCA CAGA

TTATGATAAAAAGGTTTCCCAAGATCAAGTCTGTCTCACTCAAGGGGAAGCCCAGAT TTGCA

GATTTTAATTTGGTGCCACCAAATTGGGGGGCCCATCTCACTCCATGGGTGTCGGCC ATGG

CAACTGCTTATCCATTACTTGAGAGGCTGTACTTGAAGAGGATGACTATCACAGATT ATGAT

CTCACATTGCTTGCAAATTCCTTCCTATATTTCAAGGAGCTTGTTATGGTTTGTTGT GATGGA

TTCAGCACAGGTGGCCTCGCTTCGATCGCAAGCAAATGCAGGCAATTGACCACACTT GATTT

GAATGAGGACGAGATACATGATAATGGAGAAGATTGGCTGGCTTGCTTTCCTGAGAC TTTGA

CGTCTCTAAGATCTCTTTGTTTTGATTGTTTGGAGGGCCCAGTAAATTTTGATGCAC TAGAAA

GATTAGTTGCAAGATGCCCCTCTCTGAAGAAGCTCAGGCTAAATAGAAATGTTTCTA TAGTG

CAATTACAAAGGTTGATAATAAAAGCACCACAGCTTACTCATCTAGGAACAGGCTCA TTTTTC

TATGAGTTCCAACTGGAGCAAGTAGCAGATCTTCTCGCAGCCTTCAGCAATTGTAAA CAACT

TCAATGTTTGTCAGGATTTCGTGAAGTTGTGCCAGAGTATCTACCTGCGGTATATCC AGTTT

GCTCTAATTTAACATCTCTAAACTTCAGCTATGCTGTTATTGGCAGCAGAGAGTTGG AAGGA

ATAGTCTGTCACTGTCGTAAATTGCAGCTACTCTGGGTTTTGGATTCGGTAGGAGAC AAAGG

TTTGGAGGCAGCAGCTACAACGTGCAAGGATCTGAGGGATCTCCGTGTATTTCCTGT GGAT

GCACGTGAAGACGGTGAAGGTTGTGTATCTGAACGGGGCCTTGTTGCAATCTCCGAG GGGT

GTCCAAATCTTGAGTCCATTCTATACTTTTGTCAGCGTATGACCAATAAAGCAGTTG TGACCA

TGTCGCATAACTGTTCCAAACTTGCCAGCTTTCGTCTCTGTATCATGGGTCGACACC AACCT

GATCATTTAACTGGTGAACCTATGGATGAGGGATTTGGGGCAATCGTAAGAAACTGC AAAAG

CCTAACAAGGTTGGCAGTATCCGGTCTACTCACTGACAAAGCATTTCAGTATTTTGG AGCCT

ATGGTGAAAGATTAGAGACCTTATCAGTAGCATTTGCCGGGGAAAGTGACCTCAGCA TGAA

GTATGTGCTCGATGGATGCAAGAACCTTCGGAAGCTGGAGATTAGAGACAGTCCATT TGGA

GATGTTGCCCTCTTGTCTGGTTTACATCACTATGAAAATATGCGGTTTTTGTGGATG TCTGAT

TGCAGACTCACTCTACAGGGATGCACAGAGCTGGCCAAGAAGATGCCTGGACTTAAT GTTG

AAATAATCAGAGAAAATGAATGCAATGATTCTCTTGTTGAGAAACTTTATGCTTATC GCACTG

TAGCAGGTCCACGGAAAGACATGCCGTCATTTGTAACCATCTTATAGCCACTTCACA TGAAT

TTCGTGGTTATGGCTCTGCTACATATGGGCAACCTGTTAGGGCTATCCTACTAAATT AATCAT

GCATCAATGTTACTGATGAAAAAGCCCATGTCCATAATGCCTTTACTTCACCAAAGG AGGAG

CAATAGAGCAGGCCAGGTTATTGCCATTTTACTTTGGAAACTTTCTTCAGGTTGTAG CTGCC

ACCTGAAGGGTTGGAAGAATGTACGATTCACTGATGCAGACTGCTAATTCTTGTTGC TCCCT

AAAGTTGAATCTAGTTAAATGCCAAACAATAAACTGGTGATAGAAATGCTGAAGGTG ATGAA

AGGTGGAGAATTACAGATGAATCCCTTCTGCGTGCATTGGATAGTGTTTTAAGGGAC TGAAT

GCCTCAATTGGTCTGTTTGTTTTAATTTCAAACAATTGACCTGTCTTTGATGCAATC TGTGCTT

TGACTTGAATTCAATCTGTGATTTGACTTGAATTTTATTTGCTATATGACTGATCCG GAGCTT

GTTGAGGAGGTTTGGAATTGTTCCGAGGGAAAATTTCTGAGTTTATCATGTTATACT GATTAA

TTGCTTGAATTATCAAAAAAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

173 CTGCAATGGCTTCAACACCTGTGTCTTCCTCTGCTTCTCAGCCCAATTTACTTCGCCATT ACA

CTCCCACTGTCACAGATTGCTCCTCCTCAGGCTCCTCTATCCCCGTTGTGGATTTGT CTGCA

CAAAAAACCAGTGTCGTCCAGGCCCTGGTTAAAGCCTGCGAAGACTATGGGTTCTTC AAGG

TTGTGAACCATGGAATCTCGCAGGTTTTAATTGATGCCATGGAGGCAGAAGCGGAGA AGTT

ATTCGCTCTGCCATTGTCTGAAAAGGAGAGAGCAGGACCTGCCGACCCGTACGGGTA TGGC

AACAGAAGTATTGGTCGCAATGGGGATGTGGGTTGGATTGAATATCTGCTGTTCAGA TCTGA

TTTTCAATATGTTCAGCAGCGTTATAAGGCAATTTCGCCAGATAATTATATCAATTT TTGTAAT

ACTGCCAGCAAATACATAAGTGCAACCAAAAAGCTTGCATGTGATATACTGGAACTG CTAGC

AGAAGGGCTTGGGCTTCCTGAAAATATATTCTCAAGTTTTCTAACAGCCGAGGGGAG CGACT

CTGCATTCAGACTCAACCATTATCCGCCATGCCCGGATCCTTCTAACATAATAGGAT TCGGA

GAACACACCGATCCCCAGATTTTAACCGTTCTGCACTCCAACGATGTCGGAGGATTG CAGG

TTTTATCCAGAGATGGAAAGTGGGTTACCGTGTCCCCGGACCCGTCCTCGTTTTCTA TAAAC

ATAGGAGACTGCATGCAGGTACTGACAAACGGGCGGTTCAAGAGCGTGAGGCACCGC GCG

GTGACAAACACGCTGCGTTCGCGGATTTCAATGATGTTTTTCGGTGCTCCGGCGTTG GATG

CGACCATCGTCACTCCTTCCCAGCTAGTGGACGAAGATCGTCCCGCCCAGTACATGC CATT

CCTCTGGTCTCAATACAAGAAATCCATCTACTGCTTGAAGTTGGGACAAACTCGTGG CCTGC

TCCAGAAATTTCAGGCTTCAATGGTAGGAGTAGGTGTGGCTTAATCCACTCACCAAA TTTTAT

TCCGGTGGTTACAATCCGATGATATAATGGAGGGGGAGTTGCTTGATCAAATAGCAA ACACA

GTCAGATGATACAGCGGAGAAATTGTTGTACATTTAAGATTTTTAATACAAAAAGTT TTGGAG

TAATTGAGTAAATTATCCAATATGGTATTTGACCTCCTAAACAAAATATTTACAAAT CAAAAAA

AAAA

174 TTCCGCCCTGCCTATCCTACTATCCTCCCGTTTCAGATCCGTTTCAGTTCAAATGGGTTC AA

GCGGTCGCCATGAGAATGAAGCAGAGAAGGTGGTTAGCTGTTATGAAGGGGATACAA TAGA

GCAAAACAGGGTGGATTTGATGAGAAGTATTATTGAAGTTAAGTACCCATCTGCAAA GGTGA

CAGATGATGCTACACTCAGACGTTTCCTACGTGCACGAGATTTAAATGTGGAAAAAG CTTCT

CAGCTTTTCCTGAAATATCTAAAATGGAGGCAGGCGCTTGTACCCCTTGGTTATATT CCAGA

GTCAGAGGTCTCCAACGAACTCAGGAAGAAAAAGGTTTATATTCAAGGGTTCGACAA ACAAA

GGCGCCCTATTGAAGTGATTCTTACTGCAAGGCATTATGCCTCTGACAGGGATCTAG AGGA

GTTCAAACGACTCATTGTCTATGGTTTTGACAAATTATGTGCCAGCATGCCAACAGG ATTGG

AGACATTTGTCGTCATAGCAGATTTCGAGGGTTGGGGCTATAGTAACATGGATACCC GTGC

CTACCTTGCGGCACTTGAAATTTTGCAGGATTGTTATCCAGAGCGCCTTGCAAAGGC ATTTA

TGATTCATGTACCATACCTATTCCAGACAGCATGGAAGATGATTTCTCCGTTTATTG ACAAAG

TAACCAAGAAAAAGATTATTTTTGTTGAAGATAAACATCTCAGATCAACCTTACTCA ATGATAT

TGATGAAAGTCAATTGCCAGAAATTTATGGAGGGGCATTGCCTTTAGTACCAGCTCA AGATT

TTGTCATACCCAATTGGTCTTAGATAGATCTAGTTAGGATAATTGTTATCTTTTCTT TGGTTGC

ATAATTTTATAAATTTAATTTTTTTTTATCCTTTTACATTTAAAAACTGGAAAAGCT CGAACCTT

TTTAATCTCACTAACAATTTCACTTAAACATGTTGGAACCTGCCATGCTTCTGTGTT ATCTAAA

CTTGTTATTATAACAACCATGGAAATCTAATATCCATGCATTGCCTTCCCTATCATA GGCTAA

TATTAGGAAGTCTTTTTGGTATACAGTGATATTCAATGTTAAATGGAGTGTATGATA AGTAATA

AAATATATAATATTTCCTCATATCACATGATTATATGATATTGTATCATAAAAAAAA AAAAAAAA

AAAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

175 CTTGAGGAGAGATTTGAGAGTGTTTGTGAAGGGAAGTGTTGTTGTTTGTGTGTGGGTTTG TT

ATATTTTTCAAGAAAGATGGCAATTCCAGTCATTGAGATGGGTAGTCTGATTGGAAA TGACAA

AGAGAGATTCATGGCAGAGATGGGAAAGGCATGTGAGGAAGTGGGCTTTTTCCAGCT TAAA

GGCCATGGCATACCAGTTGAGCTCATGGAGCGCGTTAAGAAAGTGTGTTCCGAGCAT TATA

ACCATGTCAGAGAGCCAAAATTTAAGACCGAGTCGGTGCCAGTAAAGTTGCTTAACA AGTCC

CTCATGGAAGCAGAGCTTTCTTCTAGCGAGCCAAAGAAGGTAGAAAATGTGGACTGG GAAG

ATTGCATTGTCCTCCAATACGCCCAAGAAGACTATCCATGGCCCTCTGACCCAAGCG AGTTC

AAGGAAACAATGATGGAATTTGGCAAAGAGATCACCAAATTGGCTGAGAGCCTGCTA GAATT

ACTAAGTGAGATTTTGGGTTTGGAGAAAGGGTATCTCAAGAGAACCCTGTCAGGAGG TGAT

GGCCCTGATGACAAGGCTTTTTTTGGCACCAAAATCAGCCACTATCCACCATGTCCA AGACC

AGACCTCGTGGAAGGTCTGCGCGCACACACTGATGCAGGTGGCCTCATTCTGCTGTT CCAA

GATGACGAGGTGGGAGGTCTCCAGGTTCTTGACAACACTGGTCGTTGGATCGATGCA CCAC

CAATGAAAGACACGTTGGTTATTGATATTGGTGATCAATTGGAAGCCATCAGCAACG GGAGA

TACAGGAGCGCATGGCATCGTGTGTTGGCTACTGACAGTGGCAACAGAATGTCAGTG GCAT

CGTTTTACAATCCATCGCTTGATGCAGTCATTTCCCCAGCTCCAGAGCTCCTTTCGC AGCCC

AAGAAAGGCTCGGAGCTATCACTGTACCCAAAGTTTATGTTCGGGGATTACATGAAT GTTTA

TGCTCAGCAGAAATTTCTTCCCAAAGAGCCACGATTCCAAGCTGTGGCAGCCTTGCA GTACT

GAGATCAMTAATATTCACAAAGCTTATGTTTATAAATACAGTGTTTCTCGGATTTTC GTATGT

TTTCTCAAAGTCGTAATAAATTTGTTTAGAAATTGTTGTACTGTTAATGCCCAACCG GTCTAG

GCCATGGCCATGAATGAACCAGGTGTGAGGCTCCAGTAAGCTATGTCGTCCAATCTA GGTC

AGGTTGCTGCATTTCTATGTCTGTATTGAGTCAAGTTGCTGCTGTCATACTAAATGT TATGTT

GGTTTTCTTGGTAGGCTTGGGAAACGTTCTGTACAAAAGACCATTTTGTATTCCTAG GCTGG

TTCTGTTTACATGGATTTGGATTTTCTGGTTAAAAAAAAAAAAAA

176 CAGGAATGGCGTCCTATATTCACATCAAGTCTTGAGGCTCCATTCAAACGAGCATTCTGG TA

CTGAGTAATTTCAGGAGATTTGGCTACATGTACGCAATCTGCCACTGGAATTAGGCT TGAGG

ATGATGGAGGCTTTACCAGATCAGGTGGTGTGGGAAGTACTAGATCGAATTAAAGAA ACAC

GAGACAGAAACACTGCAGCCCTTCTGTGCAAACGTTTCTATCAAATCGAGAAAAACC AGAGG

GAATATTTAAGGGTGGGGTGCGGTTTAAGCCCAGCAATTGAAGCCTTATCCGCGCTC TGTAT

GCGGTTCCCTAACTTAGTGAGAGTGGAGATAGGGTATTCTGGATGGATGTCGAAGCT AGGC

AAGCAGTTGGATAATGAAGGGCTTAAAATTCTGTCACAGCATTGCCCTAACCTCACT GATCT

CACTCTTAGCTTTTGCACATTTATTACAGATGGAGGTCTGGGGTACCTAGGTTCCTG CACTG

GGCTTAAGGCCTTAAGGCTGAATTTC ' ACTCCAGGAATAACAGGTTGTGGAATACTGTCCGTG

GTTGTAGGTTGCAAAAAATTGTCAACTCTTCACCTGACTAGGTGCCTCAATGTAAGC AGTGT

AGAATGGCTGGAGTATCTAGGTCGGCTTGAGAGTTTGGAAGATTTGGCTATCAACAA TTGCC

GGGCTATTGGAGAAGGTGATCTAGCAAAGTTGGGGTACGGTTGGAGGAACCTGAAAA GGCT

TCAATTCGAGGTGGATGCAAATTATAGGTACATGAAAGTATATGGACGTTTAGCTGT CGAAA

GATGGCAGAAACAATGGGTAGCATGTGAGGCTCTGGAAGATTTGAGTCTTGTTAATT GCCTC

ATCAGCCCAGGTAGAGGACTTGCTTGTGTGCTTAGGAAATGTCAAGCTTTGCAAAAT CTTCA

TCTTGATATGTGTGTTGGGGTAAGAGATGATGATTTGATAAGCCTTGCCCAGCAATG CCCCA

AGCTGAAAACCTTGTCATTACGAGTTCCTTCAGATTTCTCCGTTCCTATCCTAATGA GCAATC

CACTGCGGTTGACAGATGAGAGCTTGAAGGCCATAGCTCAGAATTGCTCTGAATTGG AATC

AGTTTCAATATCATTCTCTGATGGAGACTTCCCTTCCTCATCTTCCTTCAGTCTTGC TGGCAT

AGTTTCATTAATTGAAGCATGCCCTATCCGGGTTTTAGTTCTTGACCATGTTTATTC ATTCAAT

GACAGTGGCATGGAGGCTCTTTGTGCAGCTCACTTTCTAGAGATCCTTGAACTTATA CAATG

CCAGGAGGTCACTGATGAAGGGCTGCAACTGGTCAAGCACTTTCCATGTTTGAGTGT CATG

CGACTTTGTAGGTGCTTGGGTTTGACAGATATTGGACTCAAGCCTCTAGTAGCTTCT CATAA

ATTGCAAAAGTTAAAGGTGGAAGATTGCCCTCAAATCTCAGAGAAAGGCACTCAAGG TGCTG

CAAAGGTTGTCTCCTACAAGCAAGATCTCTCATGGATTTACTGATGGATGGTTGACC TTCATT

TTCTGAATCGTAGAATGGTCCATCCATGGATATCATTTGAAGAAATCAGTGCTTATT GACAGG

CATTTTATCAATTAGAAGGACAACTTTTATGAAAGCAGGATAATTCTAGGTGTAGTG CTATAT

GTATTATGAACAAATTTTTTGTCTCAAATTTGCTTCCTGACAGAATATGCTTGGAGT GGCCTT

TCGCATATATGTACATGCAAGGCTGTCTAGTGGTTAGCTCTTATCCATATGCTGGAC TGTTT

GAGCGTTTCAAGAGATCAGCTTTCCTTGACTTGTATATTTTCTATGTTTGATTTCAG GTTCATA

ATGTAAATACCTTTCCCGTTGAAAAAAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

177 ATAGCTATGGCTCTTCAGCTTATGGAAATGGATCTCAAAAGCAGCACCGACATGGAAATG GT

GGAGGAGGTATAAGTTATTGGAATAAGCTTCCCAAGGTCGGGTGAAGAAGGTATAAT GGAC

CCCATGGAAAGGGCTGCCAAGGTCCTGGGATCGAGTCCAGGGCACAAAAATATGATG GGC

TGTTCTTCGTCAGGTGTGAAGGTAGAACCTGAGATTGATGGGCTTCTGGCAAACGCT GGGT

ATACTGTAAAGGCCTCTGATTTAGCCCATGTTGCACAGAGGCTGGAACAACTGGAGA GCATT

ATGGGGACGGTTCAAGACCCGGGAATATCTCACTTGGCTTCCGAGGCTGTGCATTAT AACC

CATCGGATTTAGCTGGCTGGATCGAATCAATGTTCGGGGAGCTTAATCCAGGCGCAG ACAT

GCCAGTTCCGTTTGGGGACAGGGGATCTCTGATCGATTCTTCACAGGTTCATAAGCC GATT

CAGGATGATCCCAGTCTTTCTGCTATGGACTTGGCGCTCATTCATGAATATGGCTTG CAGTT

TAATGGAAGCCAAGCATCTAACCCTCAGGGTTTTTCCCCGGATTCTGATCCCTCTGT TAGAT

GCAATATTTTCTCTGGACCGCCTCTGCGTTCTGGGGATTCTACCACACACACGAACT TTCAG

GCGCGGAGCTTTAGTGCCCAGTCCAGCGACGAGGGTTCGAGTCTCTCTACTACCCGC TTG

GGAACCGCACAACAGAGCATAGATAATGGAGCGCAAGAATCAGGGATTCGCGTGGTG CACT

TGCTTATGGGATGCGCGGAGGCTATACAGAGAAACAATTTGAAGGTAGCCAGCAATT TAGT

CAGAGAGATTCGAATGACGGTGAATTCTGCCCCCTGTGGAGCAATGGGCAAAGTAGC TTCC

CACTTTGTTGAAGCTCTGGCGCGGCGGATTTGTGGATTGAATGGCGCAGAATCGAAT ATGT

CACAGGCAGATGCGCAATCGGAGATTCTCTACCACCATTTCTACGAGGTTTGCCCTT ATCTC

AAGTTCGCTCATTTTACCGCAAACCAGGCCATTCTTGAAGCTTTTGAAGGGCACGGC AGCGT

CCATGTGATAGACCTAAATTTGATGCACGGCTTGCAATGGCCGGCTCTGATTCAGGC CCTC

GCTCTCAGGCCCGGCGGGCCGCCTCTTCTGAGATTAACAGCCATTGGACCCCGGCAG CCC

GATGGCAGAGACGTGCTGCAAGAAATAGGCATGAAGCTGGCTCAGTTCGCCGAATCT GTTA-

ACGTAGAGTTCGATTTCAGAGGTGTCATGGCCGATAAGCTGGAGGATATAAAGCCCT GGAT

GTTCCAGGTGAAGCCTGGAGAAGTAGTTGCTGTCAATTCTGTTCTGCAGCTCCATCG TTTGC

TTTACATTGATGCCCCTACAGGGTCTTCCCCCATTGATGTAGTCCTCAAGTCCATCG GCAGC

CTGAGGCCCAAGATTGTGACAGTTGTTGAGCACGAGGCCAATCACAATGGACCTGTT TTTCT

GGACAGATTCGTGGAGGCATTGCATTATTATTCAACCATGTTCGATTCTCTAGAAGC ATGCA

ATGTGCTTCCAAATAGTATGGAGAAATTTTTGGCAGAGTTGTATATTCAGAAAGAGA TTTGCA

ATATTGTTGCGTGTGAAGGTCGTTATAGAATAGAGAGACACGAAACCCTTTCTCATT GGAGG

ATACGCTTGGGCAGAGCAGGTTTCAGGCCATCACATTTGGGCTCCAACGCATTTAAA CAGG

CAAGGATGCTCTTGACCTTATTTTCTGGAGAAGGTTACACTGTTGAGGAGAATAACG GTTCC

CTAACACTGGGCTGGCACAGCCGGCCCCTCATAGCTGCATCTGCATGGCAAGGCTCC TAG

GGCTTAGGGTTCAGTTAGTTGTATCATTTCTTAGCATCTTGCAGGCTCAGTAACTGT ATAAGA

GGAGAATAAATCTCAAAGTTTTCAAGTTTTTAAGACAGTTAAATACTCCTATCCTGT GGTGTC

TGGATAAACATACCAGAATCAATGAATGCTTCACAACAATGTGATACGTCTTTCTCT CTGGAT

AAGCACATTAGCGTTCAGGATGAAATGCTGGCTCGTAAGATAAATGCTACCAGAATG ATTCA

AAATGGCCATGGCTAGGCTAGGCTCATCTAAGCACTGATGTAAAGATAATGAGTCAA TCATT

TGATGTAAAAACAATGAGTCAATTATTTACTTATTGTATGGTGCTTAACATGGGCAG AAACTC

ATGCTTACACCTCTTTCTTTTTCTGAATGTATTTTCTTCTCCTTCAAAAAAAAAA

TABLE 2: Cell siqπalinα αenes seαuences (continued)

SEQ ID NO Sequence

178 ATAAGCTTAAGCTTATAGGACAGGGGAGAGGMGAGGAAGAGGGGCGAAGGGGGAAAATG

GCGTCAAATAGCAGGTATACGCAGAGCCAATCAACAGGAAGCAACAATAGGAGAAGC AGCA

CTAATACTAACACTACCACCAACAAAGCAACGGCGATGGCTCAGTACAATGCGGACG CGAG

ATTACTCCAAGTCTTCGAACAGTCCGGGGAATCGGGTAAGTCTTTCGATTACACGAG ATCCG

TCAAGTCCACAACAGAGTCTGTTCCAGAACAGCAAATTACCGCATATTTATCTCGAA TTCAAA

GAGGGGGAAGAATACAGCCGTTTGGCTGTGTACTAGCAGTGGAGGAGACCACTTTTA GGAT

CATTGCTTACAGTGAGAACGCAGTGGAAATGCTGGATCTGGCGCCCCAATCTGTCCC GAGC

ATGGAACAACCTCAACAAGACGTTCTGACAATCGGGACCGATGTTCGAACCCTGTTC ACTG

CTGCTAGTGCTCACTCATTGGAGAAGGCAGCAGTAGCCCAGGAAATAAGCCTCATGA ACCC

TATCTGGGTTCATTGTAAAAACTCCAGAAAACCCTTTTATGCAATTGTGCATAGGAT TGATGT

AGGCATGGTGATAGATTTGGAGCCCTTGAGGACTGGGGATGCGTTCATGTCAGCGGC TGGT

GCAGTCCAATCTCAGAAGCTCGCTGTGAGGGCGATTTCTCGGCTGCAGTCACTTCCT TGCG

GTGATGTTGGCTTGCTGTGTGATAGTGTTGTGGAGAATGTGAGGGAACTGATTGGTT ATGAC

AGGGTCATGGTTTACMGTTTCATGMGATGMCACGGGGMGTTGTTGCTGMATCAGGC

GTTCAGACTTGGAGCCCTATCTTGGGTTGCATTACCCTGCCACAGATATACCTCAGG CTTCT

CGCTTTCTTTTTATGCAGAACAGGGTGCGGATGATCTGCGATTGCATGGCTACTCCC GTGAA

GGTTATCCAGTCTGAGGAATTGATGCAACCTCTATGTTTGGTGGGTTCGACGCTTCG GGCA

CCCCATGGGTGCCACGCCCAATACATGGCCAACATGGGTTCCATTGCTTCGCTTGTT ATGG

CTGTGATTATTAATGGGAATGATGAGGAAGGGGGAGGGAGTGGACGAAATTCCATGA AGCT

CTGGGGTTTGGTTGTGTGCCACCATACCTCCCCGAGGGCGGTTCCGTTTCCTCTCCG CTAT

GCTTGCGAATTTCTGATGCAAGCATTAGGTCTTCAGCTGAACATGGAATTGCAATTG GCAGC

TCAGTTAACAGAGAAACACATTCTTAAGACTCAAACGCTTCTCTGTGACATGCTTCT CCGAG

ATGCCCCAATGGGAATTGTAACTCAGTCTCCCAGTATCATGGATCTTGTCAAGTGTG ATGGT

GCTGCTCTTTATTATGGAGGTATGTGCTGGATGTTGGGAGTGACCCCAACTGAAGCT CAAAT

CAAAGATATTGCAGACTGGTTGCTTGAACACCACGGGGATTCTACAGGCCTGAGCAC GGAT

AGCTTGGCAGATGCTGGTTATCCAGGTGCCGCCTCTCTTGGGGATGCAGTCTGCGGC ATG

GCTTCAGCTAGAATTACTTCAAAAGATTTTCTTTTTTGGTTCAGATCCCACACTGCA AAGGAG

ATGAAGTGGGGAGGAGTAAAACATCATCCGGACGACAAGGACGATGCTCGACGGATG CAC

CCTCGTTCCTCTTTCAAGGCATTCCTTGAAGTGGTCAAAAGAAGAAGCTTACCATGG GACAA

TGTGGAAATTGATGCAATTCACTCGCTACAGCTTATTCTACGAGGCTCGTTTCAGGA TATTG

ATGACAGTGGTACTAAMCTATGGTTCATTCTCGGCTAAATGATTTGAGATTGCAGGG CATA

GACGAACTTAGCTCCGTGGCTAGTGAGATGGTGCGTTTGATTGAMCMCTACAGCACC TAT

TTTGGCTGTAGATTATMTGGACTTGTMATGGATGGMTGCMMGTGGCAGMTTGACGG

GCCTCCCGGTTGGAGMGCCATGGGCATGTCCCTTGTTCAGGATCTTGTTTTTGAGGA GTC

TGTGGAGAGGGTTGAAMMTGCTACACMTGCCTTMGAGGGGAGGMGAGAAAAATGTT

GAGATGATGCTAMGACCTTTGGCCCACAGAAGGAGAAGGAGGCTGTTATTTTGGTCG TTA

ATGCTTGTTCAAGCAGGGATTTTACAGACMTATTGTTGGAGTATGCTTTGTGGGCCM GAT

GTTACCAGTCAAMAGTGGTCATGGATAMTTCATCCGAATCCMGGTGACTATAGGTCC AT

TGTGCAAAGCCCCAATCCTTTGATTCCTCCCATATTTGCTTCGGATGAATATGCCTG CTGCT

CTGMTGGMTGCAGCTATGGAMAAGTMCAGGCTGGACTCATGATGMGTTATTGGGAM

ATGCTTGTTGGAGAAATTTTTGGTGGTTGCTGTCGTCTGAMGGTCAAGATGCAGTGA CCAA

GTTTACAATTGTGCTGCACAGTGCAATCGATGGACAGGMATAGAGMGTTCCCATTTG CAT

TTTTTGACAAACMGGGMATATGTGGMGCACTTCTMCAGCAMCMMGMCAGATGCA

GATGGGCGAATTACTGGGTCGTTTTGTTTCTTGCAGATTGCCAGCTCTGMCTGCAGC AGG

CATTAGAGGTTCAGAGGCMCMGAGAAAAMTGTTTTGCMGATTAAMGAGTTGGCGTAC

ATACGGCAGGAMTAMGMTCCTTTATATGGMTGATGTTTACCCGGAMCTGTTAGAGGA

GACTGATCTGTCTGATGATCAGMGCMTTCGTTGMACMGTGCTGTTTGTGAGAGGCAM

TGCAGMGGTTATGGATGATATGGATTTAGAGAGTCTAGAGGATGGTTACATGGAGTT AGAC

ACCGCTGAATTTATTCTGGGAACTGTCATCGATGCTGTTGTAAGTCMGGTATGATTG TACTA

AGAGAGAAAGGATTGCAGCTGATTCGTGAGATTCCTGGCGAGGTAMGACAATGCGTC TTT

ATGGAGATCMGTMGATTGCAGCAGATCCTGGCAGATTTCTTGCTGMTGTGTTGCGGT TT

ACTCCTTCACCAGAGGGATGGGTAGCMTCMAGTATTTCCMCCTTGMACAGCTTGGTG G

TGGTTTACATGTCGTTCACCTAGMTTCAGACTTTGTTGTATGMGAGAGCCTTGATGC CAA

GATCATTCAAGAACCCACTCTCTTTCCTCCAGATAMGATATAGGATAACACATCCGG GACC

GGGCCTTCCAGCAGMCTTGTCCMGATCTGTTTGATAGATCACAGTGGGCCACACAAG AG

GGGGGTTGGACTMGCATGTGCCGGAMCTTCTCMATTMTGMTGGTGATGTGCAGTAC

ATAAGGGAATCAGGAATATGCTATTTCCTTGTGMTGTTGMTTTCCAATGGCACAMGA GAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

GATGCAGCCAGTATAAAATAGACGTGGATTCCTTGTATCATGTTCTGCCAAACAACT CTAAG

GGTTCCTTTTCTTCAACTGTAGTGCCTCTCCAGATTTGGTGCAAGCACAGCAGAGAA CTCCA

TGTATATCAATGGTATGAATGCAAGACTGAGCTTCTTTGGCTTCACAGAGGATTCCA CTTGTA

ATGTATGCTCCATTTTTCTGCTTGGCTTTAATGCTGGAAACATCGAAAGCATTGTAT CACTTG

ACTTGAGAATTCACGGCACTGGGACGGCTTTTGTAAAAGCTTCAAGTTGTTAAATCT AGTGA

CACAACCTCTCTACATGTTCCTCATGAATACTGGTAATCTGTGCTTCTGAAGGCTGG TAAAC

ATTATTATTGTGTAATCCATTAGCAAGGTCCTTGACAGCATTTTAAGCTGTAAGTTT AGAAGG

TTTCAAATTAACTGTTGTAAAACTAGCAGAGATCCATCATAGTTATAGATATATTAA GCACTGA

AAGGGATAAAAAACTGAACATGCAAAAACTCCAAGTTTTTGCACCCTCAAATTCTAT TTAATA

AACAGAGGTTTGCACGGCAAAAAAAAAA

179 CGAGGCTCCACCCTTCAAAAAAACCACCATTTCTTTTGATTAGTAATTTTGGGGTGGAGT GC

AGGCATCGAATAATTGAATAGGAGTAAATCGATTTGGAGCGTGGCCGAACGGAAAAC GATC

AATTTGGTTTCGTGAAGAGAACAGAAAGAGAAACGATTTGCCAGCCCATCCTCTCCG TAACT

TTTGACTTTTGGAATCCTGATCGGAGCATCTTCGGACGGACGTTAATGGCGACTGTG GGCA

ACMGAATGTGCAGGCCAAACTTGTGCTTCTGGGTGATATGGGGGCTGGTAAATCTAG CCT

CGTTCTGAGATTCGTCAAAGGTCAATTTTTTGCCTATCAGGAATCGACAATAGGGGC AGCTT

TTTTCTCTCAGACACTAGCTGTGAATGAAACCAGTGTGAAATTGGAGATCTGGGACA CTGCT

GGGCAGGAAAGATATCATAGCTTGGCTCCGATGTATTACCGTGGTGCTGCAGCAGCA ATAA

TTGTTTACGACATTACAAATCTAGACTCATTCGTTCGAGCAAAGAAATGGGTTCAGG AACTTC

AAAGACAAGGTAATCCAAACATGGTGATAGCACTTGCAGGAAACAAGTCTGACAtGA TAGAG

AATAGCAAGGTTTCACCAGAGGAAGCTAAAGTTTATGCTCAAGAAAATGGGCTATTT TTCAT

GGAAACCTCAGCAAAGACTGCACAGAATGTGAATGAGCTGTTCTACGAAATAGCACG GAGA

TTACCGAAGGCCGAGCCAGTGCAGCATCCTGCTGGTATGGTGCTTGCTGACAGGTCT GCAG

AAAGAGCAAGAAGCAATTCTTGCTGCTCATAATATAAGGGACATAAATATCAATGAT CAGAG

GCCTGGAAACCAAGCTGGGATAATATTTGTATTGTGCTATGCTTGAATTTAAGTAGA TTGGA

GCTGTGAGACAGATGATTATATTCTCGACTTTTCTGTTGCTAGACTGGCTTTATTTT GGGGGA

AAATCATTACTATCTGCATATCTTTGCATTTTCCTTAGGTTACTATTTTTTCGTAGA TCCTGGG

CACTGTTGAAGACTTGCCCCGAAGATCCCTGTAGTTAAACTGTACATAATGTATGCC AATGT

ATGTAAGAAATTGATTTTATCATTTGCAGCTTCTTTAATTTATGCATGTGAGTAAAT GCTTGTA

ATAATAAAGTTTTGGTCAGTTCTGCTGCTTTCCAGGTTAATATTTTGGAACTGTGAA AAAAAA

AA

180 GTCGCGGGTTCGGATTCTTTTCCCTTTCGTCACAATGGCGGATTCCTCAGTGCGCAGCGA G

AGCGTGTACATGTCGAAGCTGGCGGAACAGGCCGAGCGGTACGACGAGATGGTGGAG TAC

ATGGGGAAGGTAGTGAAGGCCGCGGACGTCGAAGAGCTGGCGGTGGAGGAGAGAAAT CT

GCTGTCTGTGTCGTACAAGAATGCCATTGGGTCACGTAGGGCCTCCTGGAGGATCGT CTCT

TCCATTGAACAGAAGGAGGAGAGCCGAGGGAACGAGGACCGCCTGCCCCTCATCAGG CAA

TACAGGCTCAAGGTGGAGGCCGAGCTGAGCGGCATTTGTGACAGCATCCTGGGGTTA TTG

GATGGCTATCTCATTCCCTCTGCTTCTTGCGGGGAGGCCAAGGTCTTTTATCTCAAG ATGAA

GGGAGATTACAATCGTTATCTCGCGGAGTTTAAGACCGGGGATGAGAGGAAAGAGGC AGC

GGATGGCACACTGGAGGCCTATAAGAATGCACAGGGTATTGCTCTGGTTGAGCTGGC CTCA

ACACATCCTATAAGGTTGGGACTTGCACTCAACTTTTCTGTGTTCTACTATGAGATC ATGAAT

ATGCCAGAGAAAGCATGTGCCCTTGCTAAACAGGCTTTTGATGAGGCCATTGCTGAG CTGG

ATACATTAGGTGAAGAATCTTATAAGGATAGCACACTGATCATGCAGCTTTTGAGAG ATAATC

TGACACTCTGGACTTCTGACATGCAAGAACAGTTGGATGATTCCTAGTGAAACAGAT AACTA

AGAAGGTGCATGATCCTCTGGTTCAAGTTGAGATAGAGGTGCCGCACTCATTAGTAG GTTTA

TCATATGGAGGTGGACTCAATGACAGTTTGGTGGTTTTATTCATTTTAGTGAGTGGA AGGAG

AGGACATTTTTATGGGTCTGCCACAGAAATTGATGGTCCGGCCAATTGTTTGGATGA TGTAT

TAGTGGTACATTGCTGCAATACTTTAATCCAGAAATTCATTACTAAATGATAACTAG ACACAT

GTGGAAGGATTATCAGATTTTGTTGGATTACACTGGTTTCAGTGTAGTTTGAGACTT TGTGAT

CCAAATCAAGTTTTATAATATTCTTATTCATAGACAAAAAAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

181 GGGAATTCCCATTCTGCACATGCAATGGACAATGGAATGATGGTATGGATAGTTTTAGCA GG

GGTAGTGGCAATGGCAGTGTGGTATCTTTTGGTACAGCACCAACAGCCTAAGCAGAG CCAC

AATGTTCCTTGGGAGACTCTTCCACCGGGGGCTGTGGGATGGCCCTTTCTCGGAGAG ATCA

TCTCTTTCTATTTCCGAACACCGGATTTTGTGAAGCAGCGGCGGGGAAGGTATGGGA ATTTG

TTTAGAACGTTCCTGATAGGATATCCAATGGTAATCTCAACAGATCCTGAGGTTAAC AAGTTT

ATTCTGAATAATGATGGCCGGCTGTTCGTTCCTGCATATCCGTCGCATTGGTCACAG ATAAT

CGGAGAGTGCAATATCTTTGCTGCTCGTGGAGACTTTCACAAGAGAATGCGGGGAGC TTTC

TTGCATTTCATCAGTATTTCGGTAGTCAAGAATCGGCTTCTTTCAGAAATACAAAAT ATCATA

ACTTTCTCTCTCGCAGGGTGGGAAGGTAGAAATGTGAATGTGTTGCATGAAGCGGAA GAGA

TGATATTTTCGGTCATGGCCAATCACATGTTAAGTCTTTCAGCGGGCACAGCACTGG AGAGT

ATGAAACGCGATTTTTTGGTTATGATGAAGGGACTTCGCAGCCTTCCGTTGAGAGTC CCTGG

CACAACGTTTTACAAAAGCTTGCAGAAAAAGCAGGTGTTGTTTAACCAAATCAAAAG CATTAT

TGAGGAGAGGAAATTGAATATGTCAGCCTATGATTCATATGACGACTTGTTATCATC CATACT

AAGAAGTGCATCAGAAAAAGAATTCACAACAACCCAGATCGTAGATTTAATTGTGCA GTCGG

TGATTGGTTCGCTTGAAACTACACCAAAGATAATGGCTTCAGTGGTGCGGCATCTAT CTGAA

AATCCACATATCATTATATATCTCAAGGAAGAACACGAAACGATAATCCAAGCCAAA GAAAAC

AACCAGAGTCTATCATGGGATGACTATAMTCMTGGTCTTTACTAAMGTGTGATCAAA GAG

ACTTTAAGATTTGGGATGCMCCTCTCMCMTATAATGTTTAAAAAGACTCTCCAGGAT GTA

AAMTTGMGGATATACMTTCCCMAGGATGGACATGCATMTATATGATTTAGTCTCCGA C

ATGGATACCMGTACTGCMAGACCCTCTTTCCTTCMTCCTCAGCGGTGGCAGAGTMGG A

MTGMTGAGGTGCCCTTTTTAGCATTTGGAGGTGGTCCTAGACTTTGTCCTGGATATG AGT

TGGCTATGTTGACTATGTCATTTTTCTTACATCATCTTGTGACAAMTTCAGATGGGM TATCT

TCCTTCGAAATCTGAGTTMGGTGGTTTGATTCACCCTTGAACTCAGTATTCGATTGC AGGAT

CCACGTAGAGMTCGTTGMTCTMAGTTAGTGAGATGMCMGCACCAMGTTTGGTAGTT

GGAAAGACTAAATGAAATCATTATGAGTATATTCTTTTTTTATTGATATTTTTAMTT AAMCTG

ATGAGATGAACCTTTGATACTCCTTTGTTGACATCAMGAGTAGATTGAAATAATTGT CAATA

TTGTTTTATTATTTGTAGATAATTTTTTTGGTTAGCTGATATTTTAMGCTAAAGTTA AMAAM

AA

182 CTTGMTCTGCCATAGCCTTATCTTCAGCTGCAGTTGMGCTGGGGTTTTGCAGATTTGGGA

ATGGCGATATTATACGCATTGGTGGGGAGGGGAACAGTGGTTTTAGCCGMTTCAGCG CAG

TGGGTGGGMTGCAGGMCAGTTGCCAGACGMTCATGGAGAAGCTTCCTCTCCAAGATC G

CGGAGMGGAGAMGTCGCCTATGTTATTCTCAGGATCGCCACATCTTCCACATATTMG AG

GATCCGATGGATTMCCTTCCTCTGCATGGCCMCGACACCTTTGGCAGACAAATTCCA TTT

GCATATTTAGAGGATATTCMATGAGATTTATGMGACATATGGCCGTGTGGCTCAAMT GC

ACTTGCTTATGCAATGAATGATGMTTTTCTAGAGTTCTGCATCAGCAGATGGAGTAT TTCTC

TAGCMCCCCAATGCAGACACCTTMCACGTGTTAGGGGGGAMTGMCGAGGTACGCACA

GTTATGGTTGAMACATAGAAAAMTCCTAGAMGAGGGGATAGMTTGMCTTCTGGTTGA

TAAMCATCMCTATTCAGGACAGCTCGTTTCATTTCAAGAAGCAGTCCAGGCGACTAC GGC

MGCACTTTGGATGMGMTGCMAGCTTTTGGCTTCATTGACTTGCTTGATTGTTGTGCT TC

TGTATATCATAATTGCTTTGTGTTGTGGTGGTATAACTCTTCCATCTTGTCGATCAT GATTTTC

ACAMTCTTGGCCATGGMCTTTCGGATGATGTTCTGTTTGCTTGTCCGTCTTTCAAGG CTAT

CTATGAMACATCATCAGTTGTGTGCCAGACCCAATCTACAGCTTATGATGGTGTAAM AGG

CTGTTTTCTTGGAGATCAGTTAGACTGATGCMTGMATTTTGCTCMGMTCTCAGGCTA CT

TGGMGCTTGGTGTGTGGAGGMGGCTTCTGTATTTATGAGAGATGTTTTCATTTGTMT GT

CTGCTCTTTTGCAGATTGGTATAGTGCACMGGTATTMTACTGCACGCGCTTCTGATT CATT

GATTMCCCATGGATATMTTTTMTGGCATTGATAMAACAACMTTTGATCGAGTTGTAT G

GCTTAMTGGATAAACATATTCCGATAMTTGATTGAGTGTMTTTCTTATTTGMGGMAT TC

TGTCTTAGAGGCCCCATATTCATTGTGTTTATCAAAAAAAAM

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

183 GCCACGGTTGCGGTGGTGGGATGCTCTCCAGCGCTACCTGAGAAGTCTCTTCTTTACAGT A

TATTTAAGAGGGAAATCGCAAAATCTGGCATCCCATTATGCGGCGAAGGGTTTGAGC TGAG

AGCATGGGCATTCTGCCACGGATACTGAAGTCGTCCCGCCTTTTCTGAGATCAATTG ATACA

CAGAAATTTTATTCGCCCCGTGTTGAAGGGTCTGGAGGAGCTTTATGTGGTAGGCAA GATTG

AATTCCGCATCAAAGCTACTGATCAGCAGGGTTTATTGGTTTCCAGAATTGGCAAAG AAATG

GGGGAATTTAAGAAATGGAAGCGGTGTAATTCACTTCCATCACCGATAAATTCCTTG GACGA

TGGGTGCCTAATGCGCATATTTTCTTTTCTCTCCCCTTTGCCAGATCGATATAGTGC TGCAA

GGGTTTGTTCTAGGTGGAGACATCTGGCATCTGACCCTCGAATGTGGTTACGTGTGG AAAA

ATCGTGCAATGCATTGGCTGAGTCGGGTATCTTTTCAACGATTGAAGATGCAGTTGT TGCTG

CAAGACCAGGAGATACCATATTAATTGCTACAGGAGTAGTTCATATGGCCTGTAATA TTCAAA

TAGTCAAGCCCATTTGCCTGGTTGGTGGAGGTTCATCACCAGATGAAACTGTGCTTG TTTGT

CCGCGGGGCTTTGATAGTGCCCTAGAGTTTCTATCCACTGGAAAAGTTGCCAATCTT ACCAT

AAAAGCAGAACTTGGAAGCTGCTTGCTACATAGAAATGGACGTCTTACAGTGGAAGG CTGT

GTACTACAGTGTGAAGAACATCCCTTGGAGCACTTATGTTGTCCAATTGTCAGCACT GCTGA

TGCTTTAGCCCCTCCTAGTACCTTGTCCTCTGTCATGAAGGGGGGAAGTTCCATGTC TGTTA

TACATACTCGAATTAAAGGTGGTGCTAAAGCAGTTTTAACCAATGGGAGCCTCACTC TGCAG

CAAGTCAGAGTTATATATTCACCGACTGCCCTGTTTTTCTGGTTTAATGTTTCACAA AAATCC

CTGACAGATATTGATTTGCCACCATTTATATGCAAAGCTTGAGTTGTCTGTGGAGGT TGTCA

GCATTTGCAGTTTCTAGCTTATTAGGTGCGACTTCATATTTGTAACATTAAATCCTG TTATCTT

ACAATTTACATAGTATCCTGGGAGTCTCTTTTAATTTCAAATATGGCTGTGGGCATG GAGGT

GTACAAAAAAGTTATGGATCTGAAACTTTTGTTTTCTTTGAATATACAAACTCTGAG TTGCCTT

TAAGCCCGGAGGCATAATTTGGGTGTCTCTGAGTTGGTAGATCATCAGGGCATAGCT TTCAT

AACCGGTAATGGAGTATATGTTCCATGCCTAACAGGTATTGAGATTCAGGTCTATGT AGTAG

TTTATCGTATACATCAATCTCTTTGGAAAAAAGAGATGCCAGACTTTAAATGATTCA AACGAG

CACTTTCATCAAGAAAAAAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

184 GCCAACTTCTAACTTCTTGGAATCTTCTTGGAATGCCCTAGATGCGTTTTAGTTACCTTC CGC

CGCTATCTTTGGCGCCTTCCACTGTGGGTTTGCAGATACATTAATCTGTAGTGCTGG GGACG

AAGGATTGTTAGCGCTTGTATCCCTGAGAAGTTCGGATACCTTGCATCACTTCAGAG GCATT

ACTCTTTTGTAATTCCAACATCATGGGATCAACAAACAACCAGTCAGAGAGAGCATT CTCCAT

CAAGCTATGGCCTCCAAGTGAGAGTACACGCTTGATGCTGGTAGAACGCATGACTGA TAAT

CTCTCTTCAGTTTCATTCTTTTCCAGAAAATATGGCCTTTTGAGCAAAGAAGAAGCT GCAGAA

AATGCAAAGAGAATCGAAGAGACAGCATTTCTTGCTGCAAATGATCATGAAGCCAAG GAAAC

CAATTCAGATGATAGCTCCGTAGTGCAGTTCTATGCAAGAGAAGCCAGTAGACTCAT GCTAG

AGGCCCTTAAGCGAGGACCCACAAGCCAGAAACAAGAATCTGAGAAGGAACTAACGG CTGA

AACTGTTGAAGTGAAGGAGACCATTTTTGACATATCAAGAGGTGATCGAGGGTTTGT CGATG

GAACCCTTGCTGAGGAGCTCCTGAGACCATTGACAGAGGAAGGGAATAGTTATACCA AGAT

ATGCTTCAGCAACCGAAGCTTTGGTCTCGATGCTGCTCGTGTTGCAGAGAGGGCTTT GATG

GAAGTTCAGAGAAATCTGACTGATGTTGATCTTTCAGATTTTATTGCAGGAAGACCT GAGGT

CGAGGCCCTTGAGGTAATGACCATATTTGCGTCTGTTTTACAAGGGTGTGAGTTGAG GTCC

CTGAATCTTTCTGATAATGCACTGGGTGAGAAGGGTGTAAGGGCATTTGGGCCTCTG TTAAA

ATCTCAGAAAACGTTGGAGGAACTGTATTTTATGAACAATGGAATCTCTGTGGAGGC TGCTA

GAGCCATCTGTGAGCTTCTGCCCTCTGTTGAGAGGCTTAGGGTTCTGCATTTCCATA ATAAT

ATGACAGGGGATGATGGAGCAGAGCCCCTTTCAGAGCTCGTTAGGAACTGCACTGCA TTGG

AGGATTTCAGATGCTCATCTACTAGGGTTGGTGCTGTGGGTGGTATAGCTTTAGTAG GAGCT

CTAGGAGCAGGAAATAGATTAAAGAAGTTGGATTTAAGGGATAACATGTTTGGGAAG AAGTG

CGGGGTTGCTTTGAGCAGAGCCCTCTCACCGCATTTGGGTCTTACAGAGGCTTACTT GAGC

TATCTGGGTTTTCAGGATAAGGGGACAATAGCTCTTGCCAACAGCCTGAAGGAAGGG GCTC

CGTCCCTCAAGGTTCTGGAGCTTGCAGGCAATGAGATTACTGTGAAAGCAGCTACGG CGTT

GGCAGAGTGCCTTGGTTTGAAAAGAATGCTTACAAAGTTAGTTTTGTCAGAGAATGA ACTCA

AGGACGAAGGATCAGTGTTGATCTGCAGAGCACTTGAGGAAGGTCACGAGCATCTGA AGGA

ACTTGATTTGAGTTCAAATTCTATCAGTGGAGTAGGGGCGAAGGTTGCAGCTGAGTT AGTTG

TCAATAAGCCTGACTTCGATCTGCTGAATATTGATGGAAATTGCATTTCGGAAGAAG GGATT

GATGCTGTCAAAGATGTCCTGAGAAGAGGTGACAAGGGTGTTACCGTGCTTGGGTCT CTGG

AAGATAATGATGCAGAGGGCGAAGGTAATGACTATGAGGACGGGGACGAGGATGATG ATG

AAAATGAGAGCAGTGATAGTGATGGTGATTTAGTGGCCAAGGTTGAGGACCTGAAAA TGCA

GTAGCGCCACGCATAGTCTTCGACATACATTACAAGGACAAATTTGGGTCTTCATTT GCTGT

GAAAACGCTGATCCCGTGAAGGCAAACTTTCAGAGTTTTAACTGCTGCAGATAAGTC CCTTT

ACATTAAATGATTGGAAATTCTATACCCGGCTAAATGTTGTTTTGTGAACAAATGAG AAATTT

GATTGTGCAGCTTTTGACTGCCCTAGCTTAAGTTCCGTTTCTAGTATTTCACGTTTA ATTATG

GTTCAGTTAGAATATGTTTATCAAATTCTTCATCATTCCTAATGATGATGGTTTTGG GTATTCA

AATTCCTTTTAATTTTCTTGCTTAAAAAAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

185 CGTTCTTTAGCCCTTTTGTTGATTGTATGTGTTGCACAGCCTTTCAGGAGGAGGAGAAGC TA

GCGGGAAAAGGCGCGCCGTTGCTGCCGAGGTTTGGCCTTTTGGAAACACGGATCTCT GCG

TCCCTTGACGGCATTGAGGATTTTGATCTTTCGGTTTAGGTTTTATTTTCAGGGAAA ATGTCG

CCTGCGGAGTCTTCTCGTGAAGAMGTGTGTATATGGCCMGCTTGCTGAACAGGCAGA GC

GCTATGAGGAGATGGTAGAGTACATGGAGAMGTTGCCAAGACAGTAGATGTGGAGGA ACT

TACTGTCGAGGAMGGMTCTGCTGTCAGTGGCTTATMGMTGTMTTGGAGCTCGCCGG

GCTTCATGGAGGATMTTTCCTCCATTGMCMMGGMGAGAGTAGGGGAMTGMGMCA

CGTTACTATGATMGAGMTACAGAGGCMGGTTGAGTCTGAGCTCAGTAATATTTGTGA TG

GCATTCTACGTCTTCTGGATACACATCTTATTCCGTCATCCACATCTGGTGAGTCCM GGTAT

TTTATCTTMGATGMGGGTGATTACCATCGATATCTTGCAGMTTTAAMCTGGTGCTGA GA

GGMGGMGCTGCTGMAGTACATTGCTTGCATACMGGCAGCCCAGGACATCGCGACTGC

AGAGTTGGCTCCMCTCACCCTATCAGACTGGGACTGGCCCTTMCTTTTCTGTATTCT ATTA

TGAGATTTTGAATTCACCAGATCGTGCCTGTACACTTGCCMGCAGGCCTTTGACGAG GCAA

TTGCAGAGCTTGATACGTTAGGTGMGAATCTTACAAGGATAGCACTTTGATCATGCA GCTC

CTTCGTGATAACCTCACGTTATGGACTTCAGACATGCAGGAGGAGACTGGAGGAGAT GAM

TCAAAGAAGCTCCGMGAAAGMGMGGTGATGGACACTGAAGGTGATGGACGCTGACAT C

TTTTTTATGMTGAMTCGATTAGGATGGTGMGGGGATGMCGTCMTGTTTATCCGTAMT

GACTGTCAAGTAGGTTAGATTCATGAGATATGGTCAAATATGTTGTATTAGAGGTTT TAGAGT

GTTTTTGTGGTTTTCTGCACGATTGTGTGCTAAGGGGGATTCAGCAMTTCTCCTATA AMTC

TGCTGCCCTGCAAGATTTTATTGTTGCAGGGTACTGCTTTGTACTCCMTCATACCAT GGAG

GGCACACTTAMGTTGTTATTTMGTGTTATTGATGTCATTTGGAAGGATCCCTGCTTGTCA G

TGGATGGATATGGTACCCTGCAGACCTGGGATTGTMTMCATAGTGGATAMTTACTGC AA

GTTCTAATATTATACTGTGATGTGCACCAAAAAAAMA

186 CAGATTTTGCATGCTCTGTCTTGATCTCTGTGCATTGGCCAACCCAMGCCAGGCCATTTT C

ATCTGTATAGGTGTTGGGTGACGTGAMGGGGCTTTCTCCGGTAAATCTTATATTTAC CCTTT

GMGGCCTMACCTTTCGCACTCCTGTACTCAAATTTGATTTTTACCATTTGGGTCTGT AATG

GAGTGTCATTGATTCTGAAACCTTTGGGGGATTTACATTTTACAGTGCMTTTTACTG AGTTT

TGTGTGTGAGCGCTGGGTTMGGTTACTGTGAGGATGGCACGCAAGGTTGATGATGAA TAC

GATTTCTTGTTCAMGTGGTGTTGATTGGAGATTCAGGAGTCGGGMGTCGMTCTTCTT TC

CAGATTTACTCGAMTGMTTCTGCCTGGAGTCCAMTCTACCATCGGTGTGGAGTTTGC M

CTCGMCMTCCAGGTAGATGGCAAGACAATCMGGCACAGATATGGGATACAGCTGGCC A

AGAGAGGTATCGGGCMTCACMGTGCTTATTACAGAGGTGCTGTGGGAGCTTTGTTGG TG

TATGATATTACAMGMTGCTACTTTTGATMTGTGMGCGGTGGCTCCGAGMTTGAGAGA

CCATGCAGATTCAMCATCGTTATCATGTTGGTTGGCMTMATGTGACCTGMCCATCTG A

GAGCTGTGCCMTAGATGAGGCACAGGATTTTGCTGAAAAAGAGGGCCTTTCCTTCAT GGA

MCATCCGCATTGGAGTCTACAAATGTGGAGAAAGCTTTTCAGTCAATTCTCGCTGAM TCT

ATCAGATTGTGAAAAGGAAATCTCTTGCAGCAGMGAGGCAGCCTCTTCTGGGCCTAG TCA

GGGAACTCCAATTAATGTCACTGATGCTGMGCAGTTGCAMAMGAGMGTTGCTGCCTT T

MGTTTATATGTGTTCCATGTAATCTAGACATTTTMGTCCATCCMGTTGTCTAGGATT MTT

GCTGTTTAGCCAMTATATGTTCTCCGMTTTCCTTGTGTGCTTTGGTTTGTGGTMCTT CTA

ACATTGGTGAGATTATTTTTATGTACTTTGAGTGTCTGACTAGAGMGCATCATCGCT AGMT

TMGGAGGATGCCTTGTMGCTCTGAMGTTAT

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

187 GCAACATTAAAACCTCCGGCACAGGTGCCTCTGTTCAGTGAAGTTCTGTTGCATTCTGTT CG

CAGTGAAGAAAAATGAACGCGGGGCCTCTCATAGCAGCTCTAAGGGACTGCCCATTG CTGG

CATTTCCCTCATGGACCGCGGCCGGAATTATTTTGGCATATTTTTGTTATATGGCTT TAGCTC

AATTTATCCTTCCCGGAAAGCAGATTCCTGGGGTCGTGCTTGCTGATAAGACGAGGA TTTAC

TATCGCTGTAATGGTTTTATCACTCTTTTTCTGCTGGTTACTCTTTTAGGAATCAGT ATGGCA

GCAGGGATCTTGTCACTAGCAGTGGTGGCAGACAAAGGTGGGGAGCTACTTTCTACA ACAC

TGATATTAAGTGCTTTGATTTCATTATTCTTATATGTTGCTGGTCACTTATCCCAAA GCAAAAT

GACTTCTTTAAAACCACATATTACGGGGAACTTTATTCATGATTGGTGGTTTGGGAT ACAATT

AAATCCACAATTCTTGGGCATTGACCTCAAATTCCTTCTCATTCGTTCTGGGATGAT TGGTTG

GGCCGTCATAAATCTATCAGTTGCAGCAAAGGCCTTCCAACTGAAGGATTCATTAAA CCTTT

CAATGATCCTTTATCAGATATTTTGTTTGTTATATGTGATGGATTACTTCTGGTATG AAGAATA

TATGACATCCACTTGGGACATAATTGCGGAGAATCTTGGTTTCATGTTGGTCTTTGG GGACT

TGGTTTGGATTCCATTCACTTTCAGTATTCAGGGTTGGTGGCTTTTAACACACAAAC CTGACC

TTACAAAAGCTGCTGCCATCCTTGATGTTCTAATCTTTATAATTGGGTATGACAGTC TACGAG

GCTCAAATAAACAGAAGCATATTTTCAAAAAAGATCCAACAGCTTGTATATGGGGTG AGCCT

CCGAAGGTTATCGGGGGGAAATTGCTAGCTTCAGGTTATTGGGGCATATCCAGACAC TGTA

ATTATCTTGGTGACTTACTTCTAGCCTTCTCTTTTAGTTTGCCTTGTGGAGCTAGCT CTTTCG

TTCCTTACTTTTATCCTATGTATCTGCTGTTCCTACTACTTTGGAGAGAGCGAAGAG ATGAGG

CAAAATGTCGCGAAAAATACAAGGAAGATTGGGTTACATACTGCAAACTTGTACCGT GGAGA

ATAATACCATACTTGTATTAGTTGTCTCCGACTTTGAATTTTTCGTTATTCAATGCA TGTTTTC

TCCTTACAGGAATTGCGAGCCTCTCGAGTCTTTGGAGAAATTTTCATCTTTATGGGC ATTGTT

CTCTAGACTGTGGGGTTCCGACCTGGGTAACTCACAGTGGAGATTGAAATGTGTATG TAAAT

TTTGTCTTTTATCTAT

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

188 CTCAATGATCAGACAACAATCTCATCCAGCCGTTCTCACATCAAATCTTGCGAACTCGGA AA

TTAGCGTTCAATATACATTGAGTAAAAGCAGATACTAGATGATACTTTAAACGCTCG GTCCCG

AGTTCGATCACTGTCGGGTCACGCAACCAACTGCCAGAAGAATGCAGAGGCCGTCGA AGAC

GTCTGTGGGCTATGCGATTCCGGACGAGGTTTTGAAGTGCGTGATGGGGTACCTGGA GGA

GCCGTGCGATCdCAGTGCGGTTTCCCTGGTCTGCAAGAGGTGGAACCGTGTGGATGC GCT

CACTCGCAAGCACGTTACCATTGCGTTCTGTTACACCATAAGCCCCTCGGATCTCGG TGCA

CGGTTCCCCGAGCTTGAGTCGCTGAAATTGAAGGGAAAGCCCAGGGCTTCCATGTTT AATT

TGATTCCCCAGGACTGGGGCGGATACGCGGAGCCGTGGATTAATGAGATTTCCCAGA CGTT

GCTCTGCTTAAAGGCTCTTCATTTGCGCAGAATGATCGTTACGGATGAGGATCTCAG GGCTT

TGGCTCGCGCCCGCGGCCACATTCTGCAGGTTCTTAAACTGGAGAAGTGCTCGGGGT TTTC

GACTCTCGGGCTTCTCGAAGTCGCACGGTCCTGCAGATCTCTTAGGGTCTTGTTTTT AGAG

GAMGTACTATTGMGATGAAGGTGGAGAATGGTTACATGAGCTTGCTCTTCATAATTC TTCA

TTGGMGTTTTGMCTTCTACATGACAGGTTTGGAAAATGTTAATGTTAATGACCTTGA GATG

ATAGCMCAMCTGTCGATCTCTGACCTCATTCMGATMGTGMTGTGATATTCTGGATTT A

AGAAATGTATTCAAGAAGGCCACAGCATTGGAAGAGTTTGGCGGTGGGTCATTTAGT AGCA

GTGAAGAGCAGGCTGTAGAACCAAATATTTATGAAATGGTTAMTTCCCTACAMTTTG ATGT

CATTGTCAGGACTGMTTACATGAGTGAGACTGMTTACCAGTTGTATTTCCACGAGCA TCTT

CACTAAAGAAACTGGATTTGCAGTATACACTTTTGAGCACAGAAAACTATTGCCAGT TGTTAC

AGTCGTGCATTMTATTGAAATTCTTGAGGTTACGMTGCGATTGGAGATAGAGGGTTA GAA

GTAGCAGCTGAGMTTGTMMAATTMGGCGACTTAGAGTGGAGCGTGGGGAAGATGAAG

CTGGTTTGGAGGGTCAGCAAAACTTTGTTTCTCACAAAGGGCTTTCAGTTATAGCTC AAGGC

TGTCCCMTCTAGAGTACATTGCTGTGTATGTTTCAGATATGACTMCTCAGCCTTAGM TCT

GTTGGTMATTTTGCAAAMTCTGAGGGATTTTCGGCTAGTCTTGCTAGACAAGAMGAA CA

AGTGACTGACCTCCCACTAGACMTGGTGTCATGGCTCTGCTGCTTGGGTGCCAMAGT TG

AAGAGGTTTGGATTTTACCTAAGGCCTGGAGGATTGACGGACATAGGCCTTGGTTAC ATTG

GAAAGTTTAGTAGCAATGTGAGGTGGATGCTTCTGGGTTATGTCGGAGAGACTGACT TTGG

GCTTCTTGAGTTCTCGMGGGATGCCCAMTTTGGAGAMCTTGMTTMGGGGTTGTTGCT

TCAGCGAATATGCATTATCTGTGGCAGCGCTTAGCTTGAGGTCTCTAAAATATATCT GGGTT

CAGGGCTACMTGCAACGCCATCTGGATTTGATCTTCTAGCTATGGAGCGCCCTTTCT GGM

CATAGAGTTTACTCCAGCTTCTCMGTGACAGTGGATGGTTTTMTTTGGMGMGMATTA C

AGAGMGCCAGCACAGATATTGGCTTATTATTCGCTTGCAGGMGACGMCAGACCATCC A

GATTCAGTAATTCCTTTMGCTTATCCTCATGGMTCGTCAGCTCCAGCATGTATATGM TAT

TCTCTTTTCCATGCATATGAATATTAAGTTGCTGTGTTATAGTTATTATTGGTGTGG ATCTATG

TACATTTTMCCTTCTMGGAGTGGAGCGTATAMTGGTTATGGTGTCAGTTATACTTCC TCG

GCATGCCTTTTGAAAACTATAMGGCAAGAAGMTTAGCCACGCATGGCCCTTGTGCCT GTC

TTCCGCCTGCMGCATGGATTTTATGCTGACTGCTTCMCGTTATATGGAGATGGATTC CTT

MTCTGTCGCATTTMGAGGAMGCCCTGCTTTGTCAMTCTTATGCCTGCTGTCTGTATA TT

ACGCAGAGGATTTGTCCATCTATAACATGATCGTCGATCGTCACTACTTTACCACAG AAATG

MTGCAGGCMCTCCTTGAGGAGCTTCTAGATCTATTCTTTCTTGAGGCTATCACATTC TAGA

AGAAAATGGTGGCTTACTCGAAGCTGAGGACTCAGAATGTATTTATGCTTGAGATTA CATCA

TATTAACATGTMGTTTATTGGMTCTGAAMTTCCTGATGTATCCATTTGTGGGACTTT CGG

TCAGTACAAAMGACTCMCATATGCCMGGATTCCTGATTTGATTTGAGGTAGAGMGGG T

TCGGAGTTCTCATTTGAGATTATGGCMGTTAGAAMTCAGAAGGATGATTAAMGCTGA AG

ATTCCTTGCATTTAGMTTGGGATCAGACTTCTAMGCTMGCCTGGTCTATCTGTATTT CTC

ATTTCACCATTGCGAGGTTTGCATCTTTAAATCATGGATTTCTTTCAATAATTTGTA GCTTTCT

CGTGCTAACAAGACAMTTTCTGCCTAGTGTGGAGAGTTCAAAGCCTACAGTTTGATT TCTTT

TTCTTTTCGCTAMGMMTTGATTCGCATAMGACAMGGACATACTGCTACTATGTTTGT A

GAATCCACAATTATTTGTACATATTCMTGTGTTTTATATAGCTTAATACAAGTAGTC TGTACG

TATCCTGTAAAMMAM

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

189 GGTTGCAGCATGCTTCTCGATTCGATGATGAGATAGTGATATATGATTACCCATATTTTA CTT

GGAGTGCAGACGCATGCCATGCTGGCATGCTCTGTGGACAACGTCGAGATTTAAGAT ACAC

CACTGGAGAAGATCTCGGGGATGACTACAAAGATCGGTGGTTAAGACCTCACATAGA TAAA

GGATGGAGTAACGGCCATTCCGCAGATTGGAACCCGCGATTCTGCTATTCATTCTTC TTCTC

CTCGACTTAAATCTTCGCAGATTTGATAGATATTCATTTGCCCGAACGTTGCTAGGG CCCTG

ACCATCAATGGCGAAGTTATATCTTTTCGTTGCGGCTTTGCTTCTACTTTCTGCTTC ATCAGC

TGCTTCCCAGTCGTTGAATACCTCCAGTGATGCGATCCCGGGGAAAGATTTCAGCAC AGGC

AAACAAAGTGTCGAGTACTTGCGATTGTTTGCGGAAGATATCAGCTGGTCCAACAAC CTGGT

GCTTGGGCTGCTAGTGCCCCGAAGCATTTGGTCGCCTCTGCCTAGGGTTTTGCAGAC ATGG

CTTCGTAACTATATTGCTGGAACTGTTGTGTATTTTGTATCCGGAAGCCTTTGGTCC TTTTAT

ATTTATTACTGGAAGCGCAATGTCTACATCCCGGCAGATAGTACACCTTCAAAGGAA CCAAT

CTTCTTGCAAATAATGGTGACTATGAAAGCCATGCCTTTGTATTGTGCTCTTCCTAC GCTGTC

AGAATACATGATTGAGAATGGTTGGACAAGGTGTTATGCCGCTATAAATGAAGTTGG GTGGC

CTTCTTATATTTTATTAACTATTCTATACTTACTGCTGGTCGAGTTTGGGATTTACT GGATGCA

CAGAGAGTTACATGACATAAAGGTTCTATATAAGTATCTCCATGCAACTCATCACAT ATACAA

CAAACAGAATACACTATCTCCTTTTGCAGGATTGGCTTTCAATCCACTGGATGGCAT ATTACA

GGCGATTCCCCATGTTATTGCTTTATTTATCATACCAACACATTTTTTAACCCATGA GCTGCT

TCTATTTTGTGAGGGAATCTGGACAACCAACATTCATGATTGCATACATGGTAAAGT TTGGC

CTATTATGGGAGCTGGGTATCATACTATCCATCACACAACATATCGACACAATTATG GCCATT

ATACAATTTGGATGGACTGGATGTTTGGAACACTTCGTGATCCAACAGCTGAAGCAA AGAGC

GTGAAAAATATGTGATTTCCAGCTTTTCTATGCAGCCGTTTCTCAAAAGATCTTTTA ACTGGT

TGTGCTGTTTACTCGCCAAAGAAACTTTTTTCTACATTTAGGGCCATAGAATAATTT TTTTTGT

ATATTCCGTGTAGGCAGATGTTGTACTTCTCGAAGTTTATTTATTTGGGAGCAATCG GCTTTT

TATGTGTAAGTTGTAATTTGTGATATCAAGCTCTGGTTTAATGTTGTAAAGACTTGG TGAGAC

GGGCTGTGGAATTATTTTTATCAACATAATTAGGTGTACTTTCATATTTCATTTTAA ATCTTGG

CTCAAATTATTGTGAAGGCATTTCGGTTCTGCTTTCTTTGTAACATTTGTAATAGGC GAAGTC

TGTCTGCTTTTTCGATGTATTTGAACTTAATTCTGTACAATAGAACATAACACATGT TTGCCAT

GTGTTTAAGATTTCCGCATGTATACCGGCACTATTAACATATGCAAGTATTCATTGA GGGTTT

TTACCACTATAGTTGGCATTGCTTTTAATGTCGGACAAAGTCCCTAATTATTTAAAA AAAAAA

190 GCTTTCTACTGCTTCCTTGGAATGTCTTCTTTCGGCTTTTTTCCATGGTAGCAGTCGTGC CTA

TCAGTTGAACCTTCTCTTCCTTACCTTTTCTTTCTTCTAACtTCTTCCATGTAATTC TTTCTTTG

GCTTTTATCCATGCTATCAGTTGTGGCTATCAGGAGTAGCTCGGTTACCTTCTGAAA TTTGCT

TCTTGAACTGGTGAAGATATATGAACGCATGCATTCAATTTGCTAGAGATAAAACGT GGCCA

ATTTCTCTATATTTCAACGTTTTGGGATTGTCGGCATTGTCGTAATGGCTTATAAAA CGGAGG

AGGACTACGATTATTTGTTTAAAGTTGTGCTAATCGGAGACTCAGGGGTTGGGAAGT CCAAT

TTACTTTCGAGATTTACTCGAAATGAGTTCAGTTTGGAGTCCAAATCAACAATAGGT GTGGA

GTTTGCGGCACGCAGCGTCAACGTGGACGGGAAAAGTATCAAAGCCCAAATCTGGGA TACA

GCTGGTCAAGAAAGGTACAGGGCCATCACAAGTGCATATTACCGTGGAGCTGTGGGC GCC

CTGCTGGTGTATGACATTACTCGCCATGTGACATTTGAGAATGTTGAGAGGTGGTAT AAAGA

GCTCAAGGATCATACAGATGTCAACATTGTGGTGATGCTAGTGGGAAACAAGTCTGA TTTAC

TGCATCTGAGAGCTGTTTCTGTTGAAGAAGGGAAATCGTTTGCGGAGAGGGAGAGCC TCTA

CTTCATGGAAACATCTGCATTGGACTCAACAAATGTGGAGAACTCCTTCACACAGGT GTTAA

CGCAGATTTACAGAATAGTGAGTAAAAGGAGCTTGGATACTGCAGAGGAAGCTTTAT CAACA

CTGCCAGGCAAGGGTCAGTCAATTTCTGTAAATGGCAAGGATGAGTTCACTACCAAG AAGG

CTGGATGCTGCTAGTTCTACCCATTGAATGCATTTTCTTTTTCTCCCCTCGTCAATA TTTTTGT

TAATCAGGTGCCATATGTTATTCTTGTAATGTTCAATTTGATTCCATATGTTACTCT TGTAATG

CTCAATTTGATTTGATTCCAGTTGACTTGTTCGAAAACGTCCATTTTTCAAACTTCC ATCAGTC

TCCAAAGGATTGATGTATGGCCATGCATTCGCTATAGCATAGTGAAGCTGGGTTTAT ACTCA

GAAGTGTAGAATCTTTGGTGTCGTATAGACGAACCATTTTGCACATTTTGAGATTGT TGTAAT

TTCTATACGTAGTACGTTTTTGAGATTTTGTGTGTTATAAAGCCACATGTTATGCTT TCCAAAA

AAAAAAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

191 CCTTCTCAACCACAACCATCATCCCCTCGCACTCTCCACATCATCTCCAGTCCCCATTTC CT

GTTTCTATTCTTCTATATTAACTATGCCTGAAACTCGTGAAGATTCCGTCTACCTCG CCAAGC

TCGCTGAGCAGGCTGAGCGTTATGAAGAGATGGTTGAGAACATGAAGCGTGTGGCTT CTTC

TGACCAAGAACTCACTGTCGAGGAACGCAATCTGCTGTCTGTCGCGTACAAGAACGT TATTG

GTGCTCGCCGCGCGTCCTGGAGAATCGTTTCATCAATTGAGCAGAAGGAGGAATCTA AAGG

CAATGAGGCTCAGGTGTCAATGATCAAAGGATACAGGGAGAAAATTGAGAGTGAACT CGCC

AAAATCTGCGAAGATATTCTCGATGTCCTCGATAAGCACCTCATTCCCTCAGCTGCC TCTGG

GGAGTCCAAGGTCTTCTACCACAAGATGATGGGCGACTACCACCGCTACCTCGCAGA ATTT

GCCACCGGTGATAAGCGGAAAGATAGCGCCGACAAGTCCCTCGAAGCCTACAAGGCC GCA

TCGGAGGTTGCCGTCACCGAATTACCACCTACACATCCCATTCGTCTTGGTCTCGCA CTGAA

TTTCTCGGTATTCTACTATGAAATTCTCAATAGTCCCGACCGTGCATGCCACCTGGC CAAAC

AAGCGTTCGACGATGCTATTGCCGAGCTTGATACGCTCTCGGAGGAAAGCTACAAGG ATTC

CACTCTCATCATGCAATTGCTTAGGGATAACTTGACGCTCTGGACTTCGGACATGCA AGACT

CTGCCGATAAGCCCGCCGACTCGAAGGATGAGCCCGCTGAGACACCTGCAGAGGATT AGA

TGTTTCCGTATGCATTTATTGTCTCGGAAGTCTTGTTATTTCTAGGCTTTTGTTCTT CAAATTT

TAATCAATCATTTGTTGAATTTGTCGTTCGTCTGTTTGCGCTCTCATTATATCTCTG CATTTGT

GTCATCCTCCATTCCTCTCATCACGTCCATGTGTCCCCTTCCCTTATTACTCCCTAT CCCTTC

CCCTCCAGTATTATGCTCGAAATGGTTTCTTATACTCCTTACCTTCAATGATGATAG AGGCGG

TTCGAGAGCAAAAAAAAAAAAAAAAAAAAA

192 CCCACTCCCGCTCAATCCGACAACTTGTTTTGATAGTCCATGTCACGTGCGGGCTGTGTT TT

CCTGAGCGACCCAATTCTCCCTACAAGTCCCGCCCACGACTATCTTTGCTTTCAACG ACCCC

CCTTCGACGCCAACATTACTCGAACTTGCTAGAATACCCTCTTTCCAACATCTATCA CAATCT

TCCACAATAGAAATCATGGCAAACGAACGCGAGAGCAAAACCTTCCTCGCCCGGCTG TGCG

AACAGGCTGAGCGCTACGATGAGATGGTCACATACATGAAGGAAGTCGCAAAGATCGGCG 1

GTGAATTGACCGTGGACGAGCGCAACCTTCTCTCAGTCGCATACAAGAACGTAGTTG GCAC

ACGACGTGCGTCGTGGCGCATCATCTCCTCGATCGAGCAGAAAGAGGAGTCAAAAGG CAC

CGATAAGCACGTCGGCACCATCCGCGATTACCGTCAGAAGATCGAGACGGAGCTCGA GAA

GGTGTGCCAGGATGTCCTCGACGTTCTTGATGAGAGCTTGATTCCCAAAGCCGAGAC TGGC

GAGTCTAAAGTATTTTACCACAAGATGAAGGGCGACTACCACCGCTATCTCGCCGAG TTTGC

CTCGGGAGAGAAGCGCAAGAATGCTGCGACCGCCGCCCATGAGGCCTACAAGAGCGC CAC

CGATGTTGCGCAGACTGAGCTCACTCCCACTCACCCCATCCGCCTCGGTCTGGCCCT GAAC

TTTTCTGTGTTCTACTACGAGATCCTCAACTCACCCGACCGCGCTTGCCATCTTGCA AAGCA

GGCATTCGACGACGCCATTGCCGAGCTCGACTCTTTGTCTGAGGAGTCTTACCGGGA CAGC

ACCCTCATCATGCAGCTTCTGCGTGATAATCTCACCCTCTGGACATCTTCTGATGGT GCTGA

ACCAGCTGAGACTGGTGAGGCACCAAAGACCGAAGAGGCCAAGCCAGCTGAGACTGC CGA

AGCCGCACCCGCCGAGCCCGAGAGCAAGCCAGCCAAGGAGGAGGAGCCCGCCGCCCC AG

CTGCAGCTTAAATTATCAGCTGACATGGACAATGCATGCTGTTGCGAACCGATTGAA GCTTG

GTCCATCATGCCTCGAGACTGCCCAATCTATGTTCTCGAGACTCAGTCGCAATGGAC ATTTC

TTCAGTTCTTCGGGTTTATGCAGGTTAACGGGTTGATGCGGTGTTCTGCTTCTTATC ATCAT

GCGAAAACTGGTTCATTATAGCAAGCGGGTTTACGAGTTCTCACACGTGTCATGTCT TATGG

GCCCCTTCTTCCCTTATCTCTCCGATCCTCCTTTGCTTTCCTGCTTTATAGCCCCGG TATACT

TTTGTTTTGTGCAATCTTTCTGGTGGGATACGCTGGTGGATGGATGTTTTGGCAGTT GTAAA

GTGAGTAGGTCTTCTATGGACTTACTCGCAAGCAGCTCGACCGTGATATCTGGGTAT AACTA

ACTAGCTATAAATTGATCATATTCAATTTGAAAAAA

TABLE 2: Cell siαnaliπα qenes sequences (continued)

SEQ ID NO Sequence

193 GTAGATAATCACTACCTTCTATTTGCAGACACCTATTTCTGTGCATCGTGCCTTTACCCT ATG

CAGGGTTTCCAAATATTTATAAATTGTGTCTCCCAGGTTTCGGATAAATTCCAGTTC CACTGC

CTCCTACGAATCCGGAATCTTCATCAGTTGCCATGGACGCTCTTCTGAAGCAATTTG AAAGA

CTTCAGAGACCAATTGATCTGGTGCAGACGCTACATGAAACCCAAGTGAAGCAAGTC CCTG

CACGCTACATCCTTCCTTCGGAACAGAGACCATCTCGTCCTCTTCAAGTCCAGCAGT CTCTT

CCTGTCATTGATCTTGCAGGTCTGGAAGATACTGATCAACGCATCAAGATTGTCAGT CAAAT

AGCCCAAGCATCTCAGGAATGGGGTTTCTTTCAGATAATAAATCATGACATACCTGT GTCATT

GCTAGAGACTGTGAAGCGTGTTTCACAGGAGTTCTTTGATCTTCCTCTTGAAGAGAG ACGGA

AACAGTGTCCTGTCAGGCCTGGTGTTCACATGCTTGAAGGCTATGGCCGGTTCTTTG ACATC

TCTGATGACACGGTCCTGGACTGGGTTGATACCCTAGTTCATTATATTTCTCCAGAG TGGGC

CAAAGCAGTTGAGCACTGGCCCAAAAACCCCTCCACATACAGAGAAACATATGAAAA ATACG

GTGAAGAGGTAATGAAGGTTATGGAGAAGTTGCTGGGTCTTCTTTCCCAGGGTTTGG GGCT

GGACCCAAAGTATATCCAAACCCTCAATAAGGAATCCCTGCTACAAGTCAGAATCAA TTATTA

CCCTCCTTGCCCTCAGCCAGATATGGTGAATGGGTTTAAACCCCATTCAGATGTCGA TATGC

TCACTGTTCTGCTGGATGATGGGGTGGACGGTCTCCAGGTTCGGAAAGATGAGGATT GGTT

CACTGTGCCCTCTATTCCTGGAGCTCTTATTATCAACATCGGGGATTTGTTACAGAT AGTAA

GCAATGGGAAATACAAGAGTGCCGAGCACCGGGCAGTAGCGAATACAAAGCAGAGTC GCA

TGTCTATGGTCATGTTTTTGAGACCACAAGAGGATGTGTTGATTGATACTGCTCCCG AACTG

ATCGATGAAGCTCATCCCAGCTTGTACAAAGCCGTTAAAGCTGGGGAGTACGAAACT GAGT

ATAATAGCAAGGATTTTCGAGGAAAAGACGCTGTACATACTTTACGTATAGAACAGG CGTAG

GAAGTCAATGTCTAGTCCTTCAATTGCATTTTTATAAGATGTCTATCTAGAGAACTA TTCAAG

GTATTTGAGTGGAAACTATAACTATAAGATAGCTGTAGGTGTTTTGAGTAAAAGATG TAATTT

GCTAGCATATTATATATGCAAAATAAACATAGGGGTATTTCATTGTTTTGAGTGGGT GTTTCA

GTGCCACGTGTTTGGGCATTTTGAGTGGGTATTTCATTGTTTTGAGTGGGTGTTTCA TTGTC

ACTTGGTTGTGTGCGTTTTGAGTGGAAGATGTAATTTAGAGGTATAATATTTTGTTT GGAAGT

CCCTACTTATTAGATTTTTGGAAATTTGGTTAAATATTGATTTGTCTTGTTTAAATT GGTTTTTT

GATATATGGATTTAGCAAGCTTAAAACTTTTTGCGACAAAAAAAAAA

194 CTCGCGTTCMTTCTGCMGTGGGCCATTTGMTTTTCCACAGAMCATAACCCTAGATTGG

TTTGGAAGGTCGAGTTCGATTCTCCAGGTCTGTATGCTTTCCTATATGTTTTTAGCC TTATCC

TTMGATCATTTTTCGGGTCTCAGAMGAGGTTGATTGGTTATMTMCCAGMTMATGATG

GAGTCTCTGCGAMACTGGTGTATTATGCTTGTGTTTCGAGAGGCCCAGTAATTGTTG CCGA

ATACMTGATTTAGGGGACGCGGAGCAACTGGCAATAGCTGTTGAGTGCTTAGGTAGA GCC

CCTCCATTCCACAGCAGATTCACACACACTATTAAAAACAGAAGATACAGTTTTCTC ATGGAT

TCTGAGTTTGTATATTATGCAATAGTTGACGAGGCCCTTCCGAAAGTGAMGTTTTTT CTTTC

TTAGAGCAGGTGAGGGATGAGTTCMGAGACTGCTCAGGGCCMGGGTTTGTCAMTAGT A

AGGACGAAATCCTGCAGGGTTGTGGCCTGGGTGATGATTTTGCCTCCACATTTAGAC GCTT

GGTTGCCCCACTCGTTGGGATCCCCCAMCCGAAAAGCGCAGGATGGAGGMGMGAAGC

MGTGCCCGCCGGCAAGAGGATGAGACCGAGACCGAGGTTTGCTCCCCCACTGCTTCG GC

ACCACTGTATGGGAAACCCCAACCTGATTCCAMCCTMAAAGGATAAAMGTCTCTCTG CT

CTATACCGCCTTTMTTTTGMGACAMCAMCACGMMGMGMGGTGAGGGATCMGTG

ACTCAGGTAAGAGAGATCATCATGGAGAGCAGTGGCAAGGCATTGGATMCGGTCAGM GC

TCGAGGTTACGGTGGATGGAAATACTGGAGGTGCTGCAGCCCTTTCTTTGCAGAGGA CTGC

TAGTATGAGMCTAMGGTCAGCAGATTGCACAGAGAATGTGGTGGCGCMTGTTAGGGT T

GTTCTCCTTTTGGATTTCGTTGTTTGCACMTACTGTTTGTTGTGTGGCTCTGCATCT GTCGT

GGTTTTAMTGCGTTTCAGACTGATGGAGTACGTCTCTTGGATAMCCTTTTCMGATGT GTA

GCTGTTTTCCTTTTAAGCTCCAATCGGCCGCTTTTCMCTGCAATCTAGTGMTCGMTM TA

TGACTCTTAAATATATACTGTAMTATAGATTTGTGGTGGCACGAAGAGGCTTCGMTA ATGT

GACCTTCATGTTTTGGGTTCAGGAGGCCACTGTATTAGTATTGCTGTTGGTTAGCCA GTGTT

TCAGAGTGTMTAGATACMATGGGCTATTGTATGGGTCCTGGGAAGATATAGGAGAAT TTG

GTTTGATTCTTGTACATTCTTCAGATGCCATATMCATTAMGGGTGCATTCGTTTGAT CAAT

GAAGGAAAACTGGTGTTGAMCACGGAAAAAAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEQ ID NO Sequence

195 GCAAAACACTCCCCCCGCCCGCCCCCCCCGCCCGCAACTCGCTCCGCCCGGCTTTTTCTC TCTCGCTCGCTCGCTCGCGATTCTTTTGCTCTTCCGCAAATCCCTAGTCGAGAGTTAGGT TT CGTAACAGTACACGGAAGATGTCGCCCTCTGATTCTTCACGGGAGGAATATGTGTACATG G

CCAAGTTAGCTGAACAGGCTGAGCGGTACGAGGAGATGGTGGATTTCATGGAGAAAG TTGC CAAGACTGTGGACGTCGAGGAGCTAACCGTTGAGGAACGTAACCTTTTGTCTGTGGCGTA C AAGAATGTGATTGGGGCCAGGAGGGCATCGTGGAGGATCATTTCTTCCATTGAGCAGAAG G AAGAGAGCAGGGGTAACACCGATCATGTCTCGATCATTAAGGACTACAGGGGAAAGATCG A GTCCGAGCTCAGCAAGATCTGTGAAGGCATTCTCAGCCTTCTTGAGTCGCATCTCATTCC TT CAGCCTCCTCTGCTGAGTCCAAGGTGTTTTACCTTAAAATGAAAGGTGATTACCACAGGT AT CTGGCAGAGTTTAAGACTGCGACTGAAAGGAAAGAAGCTGCCGAGAGCACTTTATTGGCC T

ACAAATCTGCTCAGGATATTGCTGGGGCCGAACTGGCTTCTACTCACCCAATTAGGC TGGG

ACTTGCGCTGAACTTCTCTGTTTTCTACTATGAAATACTTAACTCTCCTGATCGGGC TTGCGC

TCTTGCAAAGCAGGCATTTGATGAGGCCATAGCTGAGTTGGATACGCTGGGCGAGGA ATCA

TACAAGGACAGTACATTGATCATGCAACTTCTTCGAGATAACTTGACTCTGTGGACT TCTGAT

CTTACGGATGAAGCTGGGGATGACATTMGGAAGCTTCGAAACTGGAGTCTGGAGAGG GG

CAGCAATGATTTGCTAGGATGATGTCAGTACTTTAATGATATTTTGCACCGTCGTAG ATGCCT

TGTGGTTTGTCACAGTGAAGATTATTTATGAACTGAGAGTGCTATAAGTTGTTTCTC TAGTGT

TCCTTGATGAGATTCGGGTTGGTCTTTAGAGTGTTCTAATGGATATTACTATCTCAA ATTGTC

GGTTCCCGTGTGCGCTCTTTCGTGCTGCCTAGTTTAAATTGCACGGACCCGTTGCAT GTGAT

TATAGATTTCTTTCTTTATCAGTTAATGCTAAGACAGTTCAAGGAAAAAAAAAA

196 GATCGTCCATAGTGTGACCAGGATCAAGCGCTCTACATATCGTGCAACTATCACAATCAG GT

CACAACAATGACGGAAGGATCAAACTACGACTTCTTGTTCAAGGTTGTACTCATCGG AGACT

CTGGCGTCGGGAAATCAAACTTGCTCTCGCGGTTTACCAGGAATGAATTCAACCTGG ACTC

CAAGTCTACCATCGGAGTCGAGTTCGCTACTAGATCTGTTCAAGTAGATTCCAAGAC AGTCA

AAGCCCAGATCTGGGATACGGCGGGTCAGGAGCGATACCGTGCTATCACTTCAGCCT ACTA

CCGAGGTGCTGTCGGGGCTCTTCTCGTATACGACATTGCCAAGCACCCCACATACCA GAAT

GTGCACCGGTGGTTGAAGGAGCTCCGTGATCACGCAGACTCCAACATTGTCATCATG CTTG

TCGGGAACAAGAGCGATCTCAAGCATTTGCGAGCTGTCCCTACAGACGAGGCGAAAG CCTT

TGCTACCGAGAACAACTTGTCGTTCATCGAGACGTCGGCATTGGACGCTTCCAACGT CGAG

GCCGCTTTTCAGAATATCCTGTCTGATATCTACCACATCGTAGCAAAGAAGAACCTC GAGAA

CTCGAGCGATGTGATTCAGCCGTTGGAAGGCCGCGGCATCGATATCGCAAAGTCGGA GGA

TGATGGCGGTGCCAAACAGGGCGGCAAATGCTGCTAAAGCGAGTCTCACCCCAGGGT TCTT

GATTTATGTGATCGGCTCGATTTATGCGGCGTCACTTGATTGCGCGCAGCCTGTCGG ATGT

GATTCTCGTCTACATCCCGAATCCGACTATCTATCACGCTTTCCTTTCTTTTGTCAC CATTCT

TGTATGACTTGTAAACAGTACGCAGATTCGATATCCTATTCGGCATAAAAAAAAAA

TABLE 2: Cell signaling genes sequences (continued)

SEξQ ID NO Sequence

197 CTCAATGATCAGACλACAATCTCATCCAGCCGTTCTCACATCAAATCTTGCGAACTCGG AAA

TTAGCGTTCAATATACATTGAGTAAAAGCAGATACTAGATGATACTTTAAACGCTCG GTCCCG

AGTTCGATCACTGTCGGGTCACGCAACCAACTGCCAGAAGAATGCAGAGGCCGTCGA AGAC

GTCTGTGGGCTATGCGATTCCGGACGAGGTTTTGAAGTGCGTGATGGGGTACCTGGA GGA

GCCGTGCGATCGCAGTGCGGTTTCCCTGGTCTGCAAGAGGTGGAACCGTGTGGATGC GCT

CACTCGCAAGCACGTTACCATTGCGTTCTGTTACACCATAAGCCCCTCGGATCTCGG TGCA

CGGTTCCCCGAGCTTGAGTCGCTGAAATTGAAGGGAAAGCCCAGGGCTTCCATGTTT AATT

TGATTCCCCAGGACTGGGGCGGATACGCGGAGCCGTGGATTAATGAGATTTCCCAGA CGTT

GCTCTGCTTAAAGGCTCTTCATTTGCGCAGAATGATCGTTACGGATGAGGATCTCAG GGCTT

TGGCTCGCGCCCGCGGCCACATTCTGCAGGTTCTTAAACTGGAGAAGTGCTCGGGGT TTTC

GACTCTCGGGCTTCTCGAAGTCGCACGGTCCTGCAGATCTCTTAGGGTCTTGTTTTT AGAG

GAAAGTACTATTGAAGATGAAGGTGGAGAATGGTTACATGAGCTTGCTCTTCATAAT TCTTCA

TTGGAAGTTTTGAACTTCTACATGACAGGTTTGGAAAATGTTAATGTTAATGACCTT GAGATG

ATAGCAACAAACTGTCGATCTCTGACCTCATTCAAGATAAGTGAATGTGATATTCTG GATTTA

AGAAATGTATTCAAGAAGGCCACAGCATTGGAAGAGTTTGGCGGTGGGTCATTTAGT AGCA

GTGAAGAGCAGGCTGTAGAACCAAATATTTATGAAATGGTTAAATTCCCTACAAATT TGATGT

CATTGTCAGGACTGAATTACATGAGTGAGACTGAATTACCAGTTGTATTTCCACGAG CATCTT

CACTAAAGAAACTGGATTTGCAGTATACACTTTTGAGCACAGAAAACTATTGCCAGT TGTTAC

AGTCGTGCATTAATATTGAAATTCTTGAGGTTACGAATGCGATTGGAGATAGAGGGT TAGAA

GTAGCAGCTGAGAATTGTAAAAAATTAAGGCGACTTAGAGTGGAGCGTGGGGAAGAT GAAG

CTGGTTTGGAGGGTCAGCAAAACTTTGTTTCTCACAAAGGGCTTTCAGTTATAGCTC AAGGC

TGTCCCAATCTAGAGTACATTGCTGTGTATGTTTCAGATATGACTAACTCAGCCTTA GAATCT

GTTGGTAAATTTTGCAAAAATCTGAGGGATTTTCGGCTAGTCTTGCTAGACAAGAAA GAACA

AGTGACTGACCTCCCACTAGACAATGGTGTCATGGCTCTGCTGCTTGGGTGCCAAAA GTTG

AAGAGGTTTGGATTTTACCTAAGGCCTGGAGGATTGACGGACATAGGCCTTGGTTAC ATTG

GAAAGTTTAGTAGCAATGTGAGGTGGATGCTTCTGGGTTATGTCGGAGAGACTGACT TTGG

GCTTCTTGAGTTCTCGAAGGGATGCCCAAATTTGGAGAAACTTGAATTAAGGGGTTG TTGCT

TCAGCGAATATGCATTATCTGTGGCAGCGCTTAGCTTGAGGTCTCTAAAATATATCT GGGTT

CAGGGCTACAATGCAACGCCATCTGGATTTGATCTTCTAGCTATGGAGCGCCCTTTC TGGAA

CATAGAGTTTACTCCAGCTTCTCAAGTGACAGTGGATGGTTTTAATTTGGAAGAAGA AATTAC

AGAGAAGCCAGCACAGATATTGGCTTATTATTCGCTTGCAGGAAGACGAACAGACCA TCCA

GATTCAGTAATTCCTTTAAGCTTATCCTCATGGAATCGTCAGCTCCAGCATGTATAT GAATAT

TCTCTTTTCCATGCATATGAATATTAAGTTGCTGTGTTATAGTTATTATTGGTGTGG ATCTATG

TACATTTTAACCTTCTAAGGAGTGGAGCGTATAAATGGTTATGGTGTCAGTTATACT TCCTCG

GCATGCCTTTTGAAAACTATAAAGGCAAGAAGAATTAGCCACGCATGGCCCTTGTGC CTGTC

TTCCGCCTGCAAGCATGGATTTTATGCTGACTGCTTCAACGTTATATGGAGATGGAT TCCTT

AATCTGTCGCATTTAAGAGGAAAGCCCTGCTTTGTCAAATCTTATGCCTGCTGTCTG TATATT

ACGCAGAGGATTTGTCCATCTATAACATGATCGTCGATCGTCACTACTTTACCACAG AAATG

AATGCAGGCAACTCCTTGAGGAGCTTCTAGATCTATTCTTTCTTGAGGCTATCACAT TCTAGA

AGAAAATGGTGGCTTACTCGAAGCTGAGGACTCAGAATGTATTTATGCTTGAGATTA CATCA

TATTAACATGTAAGTTTATTGGAATCTGAAAATTCCTGATGTATCCATTTGTGGGAC TTTCGG

TCAGTACAAAAAGACTCAACATATGCCAAGGATTCCTGATTTGATTTGAGGTAGAGA AGGGT

TCGGAGTTCTCATTTGAGATTATGGCAAGTTAGAAAATCAGAAGGATGATTAAAAGC TGAAG

ATTCCTTGCATTTAGAATTGGGATCAGACTTCTAAAGCTAAGCCTGGTCTATCTGTA TTTCTC

ATTTCACCATTGCGAGGTTTGCATCTTTAAATCATGGATTTCTTTCAATAATTTGTA GCTTTCT

CGTGCTAACAAGACAAATTTCTGCCTAGTGTGGAGAGTTCAAAGCCTACAGTTTGAT TTCTTT

TTCTTTTCGCTAAAGAAAATTGATTCGCATAAAGACAAAGGACATACTGCTACTATG TTTGTA

GAATCCACAATTATTTGTACATATTCAATGTGTTTTATATAGCTTAATACAAGTAGT CTGTACG

TATCCTGTAAAAAAAAAA

TABLE 3 Cell Signaling Protein Sequences

TABLE 3: Cell signaling protein sequences (continued)

TABLE 3: Cell signaling protein sequences (continued)

TABLE 3: Cell signaling protein sequences (continued)

TABLE 3: Cell signaling protein sequences (continued)

TABLE 3: Cell siqnalinα protein sequences (continued)

TABLE 3: Cell signaling protein sequences (continued)

TABLE 3: Cell signaling protein sequences (continued)

TABLE 3: Cell signaling protein sequences (continued)

TABLE 3: Cell signaling protein sequences (continued)

TABLE 3: Cell signaling protein sequences (continued)

TABLE 3: Cell signaling protein sequences (continued)

TABLE 3: Cell signaling protein sequences (continued)

TABLE 3: Cell signaling protein sequences (continued)

TABLE 3: Cell signaling protein sequences (continued)

TABLE 3: Cell signaling protein sequences (continued)

TABLE 3: Cell signaling protein sequences (continued)

TABLE 3: Cell signaling orotein sequences (continued)

TABLE 3: Cell signaling protein sequences (continued)

TABLE 3: Cell signaling protein sequences (continued)

TABLE 3: Cell signaling protein sequences (continued)

TABLE 3: Cell signaling protein sequences (continued)

TABLE 4 Cell Signaling Oligonucleotide Sequences

SEQ ID NO Sequence

395 ATGGTCTTATGCGATGGTGCAGTTAGTAGACTGTTGGTCTGTATTTACTTATTTAACAGA

396 TTTACCTTAAGATGAAAGGTGATTACCACAGGTATCTGGCAGAGTTTAAGACTGCGACTG

397 AATAATTCTATAGACTCACACTACCAATGGTTCACAAAGTGATTGTGGTAGACATATGTC

398 ATTAATTATGCAGCTTCTAAGGGACAATCTGACATTATGGACTTCTGACATCCCTGAGGA

399 TCTTAGTGGGCGCTGGATTGCATCATCAGACGGGTCAAATAATATATAATTAGAAGTGTA

400 ATAATGTGTAATTCCAAATTATGAGGTATATTTGCAATAAACAAAATGCAGGTCATTTTG

401 GAACATAGACGAACTAGCTGCTCTGGACACTATAGATGCCGGGAAGCTATTTAGTGTCGG

402 GGTCGGGAAGACGTCTCTCATGAACCAGTACGTCAACCGCAAGTTCAGTAACCAGTACAA

403 AATTGGAAAACGCTCTTGGGTTTGTGAACGTGCTTCTCACTGCTTTAGTGTTGGTTTTCA

404 AATTCTGCATTGAGTGTAGCAGATCCCTTCTATTAGATTATTCATATGACTATGTGACTG

405 TTCAATATCTCAATTGAACACGATAAAAGGCCTCCATGTCTATGCAGATTGTTGCCTACT

406 GTGGTCTGCTACCAATCTTTCTATGATAATGGTACCGTTTCTATTATATTAGAGTATATG

407 TTGCACTGTCTTATTTTATCAATTTGTATCCTAATACGTGGCCAATGAACTTTACGGTTT

408 AAGAAATATATAACAATGTGAGCAGGAAGGTTCTAAATTCAGATGCTTATAAAGCAGAGC

409 TTCAGTTGCACAGTAAACATGTCTGTATCCTGTGCAGTAGGACTCTTGTAACTAGTCTGT

410 TTTTGAAGGTTAATAAAAGTATTACGCTAGAACAATTACAGAGGCTGCTTGTCCGTGCTC

411 CTCAAGAACTGTAGCATATGTTATGACCATTGCAAAGGTTTTAACTGCTGCGGTATCATG

412 AAATCGTGCGTTGTGAAATTGGTTGTGTATAATCTCTAGAATCCAAAGGCTTACGGGTCA

413 GAACTGTCTTCGGGCGAGTTTAATCATGTATCTGATTTACGATCGGTGTTGTGAACGTCG

414 TCCCAACCGTTGGGGGATTTTTTGACGAGTCAGTACCAAATTTATAGTTGCCTACTGACC

415 TATATTTTTCTCTTACACAAAATGTCGTCAGATATAAATTGGTCTGGGAATTGTCGATGC

416 TGCATTGGATTCTACCAATGTCGAGAGTGCATTCTTGACTGTCTTGACCGAGATATTCAA

417 TGTATCAGATTCTACGTGGACTGAAGTATATCCACTCTGCGAATGTTATTCATAGAGACT

418 TCCATGTACTAGGTTTCCTATCTAACCTGTAAATAGCCTTATTGCTATGAGACTTCAGGC

419 TTGAATCTTAGTTATGCTCCTGGGATCCCTGGAAGTGAGCTAACTAAGTTAATCCGTCAT

420 TATGTAGATCTTTGTGGCTGTAACATGTACTTCTTGCTTACCTGTTCGATGCTATATAAT

421 GAGTGCCACAGGATTACCCTGTCAGGACTATATGGTCTTGTCGTTGGTTGTGGGGATAAA

422 CAACTTGTCGAATCACTTCGCAACCGGATTCAAAATGAGGCTACTGTTGCATACTACTTG

423 TGTTTTTAGGACACAATGTATTAGGTGCTTGATGCTAGCGCGGACACATTGTATTATTTT

424 CATCAGACGGTGAATCCAAAGTATTTTACTATAAGATGAAGGGAGACTACTACCGTTATC

425 AAAGATAACTGATTTACCCCTGGACAATGGTGTCAGGGCTATTTTAAGGGGATGTGAAAA

426 AGATTCTAACATAGTTATTATGATGGCTGGGAACAAGTCTGATTTGAACCACCTAAGAGC

427 TATTTGAACTCTGTCCCAATATGTACTTTGATTTATGGATTGTAACGATGTACTCAATTG

428 GTCATTGTGACTCATGTTAGTATTTGACATGATTCGTGTTAAATTATTTATGAAATATTG

429 AGAATTGGTCCGTGATAGTGCCACCQGAGGTTGAGATCTATGAGCTTAAAACTAATGCTT

430 GGAGTCTTCAACGGCGGTGATGTAAAATATCTATCCCAATGTATACCTCCTGTCCTGGAA

431 ATGAGGGAGTTAATTTATAGGGAAGCGCTTGCATTTAATCCCGAGTATCTACAGTAATGG

432 TTTTTAAGAAGTGATAATGCACGAAGATATGTAAGACAGCTTCCACAGTACCCAAGACAG

433 TGCAAGGGTATCGACAGTCTGCATGTCGTGAAGGTCCCCGAGTGTTCGAATTTAGGTCTT

434 GCCAGATGTCTAATGCGGCCTTACTTACCATAGCTCGGAACCGTCCTAACATGACTCGAT

435 ATGATAGTAACTGGCCAGAACCTGACCGTGTGGGACGGCAAGAACTTGAGATTGTAATGG

436 TTTCCAGACTATTCTCTCAGAGATATACAGGATAATTAGTAAGAAGCCTCTGTCCTCAGA

437 AATCCGGGAGGGTGTACCAGGACTATTGTGAGGCCATGAGCAGACTGTCTCTAGGAATAA

438 CCCTTGGGATGCGTATACGATGCGGCTCAAGGTGTATCAATTCGTGTTACAGATACCATT

439 TTTGTAATCCCCCTGAATAATGGAGTTACTATTGATCAGTGGATATTGCTTACTATGTTG

440 GATTTTTAACCCCACGGTTGTTTATGATCACTTGGGCGAAATATACTCCGCACTCATTGT

441 GACAAGTTAAGACTATTCTAGAACCATATTTAGCAGTGGTCTGTAAGCAGGTCTTACAAG

442 CAGCGTCGGCCACTCTCGATAAAACTCTGGCCGCCTAGTCAAAGTACTAGGATTATGCTT

443 TCATTCCTTATGCAGTTGTGGCAATAGATTTGCCATGTTAAGTAGTGAATAGAGAACCCT

444 TGATCCTGGCGATGCGTTCTTGGTGCCAACCCCTTACTATGCAGGATTTGATCGAGATTT

445 TTCTTGTTGGTTCCTGCATTGAGAGAGACCTAATTGCTTGATGTCCTGTAATTTGTAAAA

446 CTTTACATGGTCCTTCATTATACTATAGCCTATAGAAGAAATACATTTGCATGTATAGTT

TABLE 4: Cell signaling oligonucleotide sequences (continued)

SEQ ID NO Sequence

447 TCTCTAGATCCTTAGATTAAGGTTTGATCTGTGTATATGCTGTGTCGTTGCCTGAGAATG

•448 GGATGACGATTTGTTTCAAGATCGTTTTAGCATTGCATACAACCTTGACCGAGAGTTTGG

449 CTTGACTCGATATCTTTGTGCTGTTGTCTGTAGTATATATCAGTACCAGTTAGTTTTACT

450 TTGGATTTGCTAGGATCTAACTGCCTCACGTTGGAGAGACTGGCGTTTTGCGGTAGCGAT

451 CAAAGCAGATACAGCTGTTGCCAAAAGTCTGAATAAGGAGTTCGGGCCAATTATGAAGGA

452 CGACTCTAACATTGTTATAATGCTTGTGGGGAATAAGGC-TGATTTGCGACATTTACGTG C

453 CTGCCTTAGCATTAACGGGAACCACATGGGTGTGCATGTGTGGATTATGAAAGAGTATGG

454 TTCTTTTGAATTCGCTATCCAGTGTTGGTCAAATTTTAGCCAATAATTTAAGTTGTTTCT

455 ATGGAGCTAGTCGTTTGACTAGTACCTGTATGTAGATCTAATGGAAGCTACAGAGTTCTG

456 TTCGATGCGAAGTCTAATGACTATCGTGTTGTCAGGATTATCCGATACCTAGGTATTCGC

457 AAGAATCTTGAAGTAGGTGAAGAGTAGGATATGTTCTTTCTAGTTTAAGGTAATTTGAAT

458 GATGCTTCGGGCAGTGAAATTGCTGTTCGAGAACTAATGAAGGAACCTTCTTGACTAGTT

459 GTTCACTTCATTACGTTTTATGCGCCACTCTGGGGAGCAATCCTTTATAACGGTTTTTCA

460 GTTTTGCTCCTGTACCGTGAGACTCTCGTTTGGTACGATTTAGATACCGGTGACGTTGAG

461 AAAGGCGACTCGTGTTCATAGAAACATCTGCTAAGACTGCCACTAATGTTAGCAAACTGT

462 GGTCTTGTGGTTATATATGCCAGTTGTCTCTTTTACAGTGAGTTTTGTGTAACTCCTAAA

463 GACAGAGATCGCTAAAACCATAGAATCCGAGCTACAGAAGTTTGAAAACGGAAGTGGGAT

464 GAATCTCATTCTGACCCTGGCTCGTGAATACTTTCATATGTACACAGTATTTCACCGGAC

465 GGAGTTGTGTAGTGTTACTCTCCCGAATCAGACATTAAACACTTACTTCTACATGAGGCC

466 TGTTACTAAGAATAGGGTCTTGTTTCATGGTCTACTAATGTAATGAATCTCGCTCTTTAT

467 ACTTTCAGTACAAATAACTCACTCGTTCAATAATTTCCGTGGGCTGTGTTAATTTTAAAG

468 AGAGCAGTGATGGTCAGGCATATAAAGTTTATGTTTACCGCACTGTTGCTGGACCAAGGA

469 GATTAATTAMTCGGATTCCCCGAAATGGGATGACGTGCTATAAGGACGTAGCCACTGCC

470 GAACAATCCGCCCATGTACAGGGAGACCTCTTTCACAGAGTATTTTGGGTATTACCTCTC

471 ' TCTCTGCTCATTACCGTTTCAGTGGCTGATAATGGATTCCCACGATGCAATTGCGATGAC

472 TAGAAAATGCCTTTGCAGAAGTGCTAACGCAGATCTACCGTACCACTAGTAAGAAGACAG

473 GTTTTGTACTATTGGCGTTTGGCAGAAGTTATTTGGCCAGTACGTAGCTGGCTAAACAAG

474 TTTCACGGGGCATCTCTACACTGATGTAAATAATGTACTTATTTATAGCTGACAGTCGAG

475 AATTATTAAAGTGGACATCGTTTGTTTTATGTGACACACCTGACACTAATATTCGTAATT

476 TCTCCTAGTGTTGGTGTACTGTTGTAATCAATGGAAAGGTATGTTAGGCGACGATATTAT

477 CTTGGAAATGCTTACTTGCGAGTATCCTTACATTGAATGCACCAATCCGGCTCAAATTTA

478 TTCCTCTGGTGCTTCTACATTTATTACCTCAAGCGCAATGTTTACGTCCCGAAGGATGAG

479 TGGTAGCATCGGTAGACTACATCTATGCTGTAAACTATTCCTATCCTATAATAGTTGCAT .

480 CCAATCCAATGTTATTTCTTATTAGCGCTAAGACCTTACCTCTGGATCCCTTCGTTGAAA

481 TAGATTGATCGATTTGAAGGCTATCTACTTTCAAAAGGATACATGTTGTGCTTATGATTA

482 AATCAAATGCATTCTTGAGTGATGTCCTACTTAATTTGTCTTTCATGACGCGGCTTTTCT

483 GATGTCGTTTGGTATGATTTACATGCTAGGTACATCAATAGGGTAGATATAAGGGGCATG

484 AGTTTATTAATGTAGGATTTCCCTTTTATAGTTAAAAGAGTGATTAGGTGGGGTTAGACC

485 ATATCACAGAGCGTCCATGGTCTGCCACTATCTCTATTTGACAATTTGTAATATGTAATT

486 ATATACGTTTACACGAGAGAAATAAATTACAATCTGCGATTATATCCCGATCCACTAGCT

487 GGTCCTTCAAAGTACGTGGGCTCAAATAAAGCGTTAATATGTATGGTAACTGGTACTTCA

488 GGGGTGTTAATCAAACGTTTACTTGTGTAACCAGTGTAGAGATAGAATTGTACTCTAGTA

489 GAAGGGCTGACAGATACAGGTCTTGGTTATATTGGCGAGTACAGCACTAATGTAAGGTGG

490 GAAATACCAAGGGCACTAGAGTTCAAGTAGACGTTTATAATTTAACCGGCCATTCAACAT

491 TTCAGTGGGGCAGAGACTCTGATTGCGTACAGCAACTTTAGTGTATTATATCAAGGTCAT

492 AGAACGAGTTTATGCATGAGAAGCTATGATCCCATGGTTATTAGGGTGTAGGTCATTATT

493 TGAATATTGTACCTGAGAGCATTCATTGACTTGTAATGAATGTACACTCTCTTGGTCTCT

494 TTGTACTAGACTATACTATGGGACGCCTAACCTGTCATTTAAAAATGTGAGACTGTTCGT

495 ATTGTGTATTCCTAATCTGAGCCAACTATTGGCCTCTACTTTATTATCATTGGACATTAA

496 TCAATACTTTCCAAGGGGTTCGCAAGGTCTTTTGCAATGTCTAGCCAGATTATTCCATGT

497 AGAAGCCCTTCCGTGTCTTCGATATACGTGCCCGATCTTGTAGACAATCTTTAGTATATG

498 TCTTTTGGCATAGTGTTTCCTGATGCACGGTGCAGATATATGACTTGGCATCTAGATCAG

499 GGAAAAACTTTGACCGATTTCTGGAATCACTTATAGTTGAATTCGAGCAGGTTCTCATTT

500 ACAAAAGACCAGTAGGACATTATGGGGTCTTAACTTGGTGTGTATACCATGGCTATTAAA

501 TTGGCGAATCTACTGTTTTCTACTATAAAATGAAAGGAGACTACTACCGTTATCTGGCTG

TABLE 4: Cell signaling oligonucleotide sequences (continued)

SEQ ID NO Sequence

502 GTGAAATGTGATAATCTTATAGTGTATTAGGATTAGGATTAGATTACCAGGCTTTCCTGC

503 ATGGTAGTTTACCAGATTATATGGTTACTATCAACTGTTCGATTGTTCTAGTGTGCAGTA

504 TCAGACGTTAGAACTCTGGTTAGCTGTGCATCCTATAGTAACGTCTCTGTAATACGGTGT

505 AATTTGGAACTCAATTATCATGGCCATATCAAATGCGAAATGAAGGGTGTCATTGTTTCT

506 TTTGTGCACCCTGTTACAACTCGCCAGTATAGGTCTAAATCTGCATTTACACAACCCACT

507 AGATTGGAGTTGTGTATTCTAAATCGAGGCCAGCTATTGGGCCTTATGCGATTATTATTA

508 GGTTCTGGTTATAAACTTATGTTCAATAAAGAATTAQAATTAGATTAATCTATATAGGAA

509 TTCAGTCATCCTAAACTGCAGGTCTACTTCCGAGAGTTGTTGAAACCCGTTTAGATTCTA

510 ATTCGAACCTCGACTATTCAGTTTCCGATGCGGTCAGAGACAAGCTGCGGCTTATGAGAG

511 GGTTTAAGTTAGGTTGGAACTTTGAAGTACATTAGTGTTCTGCACTTTATATCCTAAGTT

512 TTATTACATTACCTGGGTAAGAAGTGGAGTTTAGCTGCTCAGAGGCAGATAGTAACAAGC

513 AGCTATTATTTGTTTGAGGAGCAATGGACATGACACCTACATATTTATTTAAGGTAGGGA

.514 GAATTTCCGTGGTTATGGCTCTGCTACATATGGGCAACCTGTTAGGGCTATCCTACTAAA

515 AATAAGGTGGATTATTAAATCGCGTATTTTTAACTTATCTAATATCTATTTACTGACTCG

516 GACATCTCCGCTCTTTAGTTAATGGGTCTCTCATTTCCTGAACGTCTAGGCAGGCCTATC

517 GCCTTTCTAATCGAGCAGATATTGATGGACTGAACACGATGTGTATATGGAGCGTGCTTT

518 TTAAAGGGCTGAAGAGAAGTCGATCGGTGTACGTTGTTGTCGTCAGGTTGCAGGTTCGAA

519 TAATTGCCCCGCTGTGGACATATAAATATCATGTCCGTTGGTGTGAGTAGATATCATGTC

520 TTTCGATAATTCAATTTCCGACGCGGTCAGAACCAAGCTGAGGCAAATGCGAGATGTCAT

521 ACTGTTGGTGGAAATATGTGATGCCAAATGCTAGGAAAAATTATTTAGATATTATTGCAT

522 ATTTTACGGAGAGCATAAGCTATAAAAGCAAATCGGTCTGCAGTGTATTATCGACATCCC

523 CTTCTTACTGCTTCAGCTCTACAAATTAGTGTGGGGGGCGAGCAGTCGAGCCTATAAGTT

524 CACTTGGCACCCTGCGGACACAAGTCCTAGGTTTAATCGCATATGTTGGCGTGACTAGAT

525 TGACTGATTTGCTTGGCACTCCGTCAACAGAAACACTTTCTAGGATCCGCAATGAGAAGG

526 GCATGTCAGTTTTAAGAGACAAGCACCCTGCTATTGCTCTGTATGATTTATTAGTGAACC

527 AGCTTGCACCAACGTAGGTCACCAGTTAATATGCATTCTTCTTTCAGAAATTCAAGGAAG

528 ATAAGTTTGTAGCTATCAACATGACTAAGCTTTAGTGAAGGGCTATACAATGCATCTTTA

529 GGAGGCTATTGGTTAATACATATAAAGGGTGGTAAAGCGCTGTTCATATTTTTCCTAGAA

530 GGAAGAACTTTGCGTTTCCCTGCATTTCTACTTGTACCCTTATTCATTCATTCMGAAAA

53.1 ATCTTGATTACTTGGCAGTCCTTTCTAGATACAATCCTTTCGAGGCATTTATATTCATTT

532 GTGCTGTAGATATGTTCAAGAGACAATTTGCTCATCTAGAGGAACACTATAGTAAAGGTG

533 CCAGAACCTACTAAACTGGATGCTAAATGAGCCAGACGTTCCAAATAATAGACAGTTAAC

534 AGACCTCTTAATCCATGGTGAGAGCATGAGGTCTAATAAGTTCGGAACCGTGTATTCATC

535 AAGTAACATTTTGTGCAGACAGTGGTTACAACTTTGAAAATTGGAAGCTGGGCTATTTTC

536 TTTTCGAAAGCTCATCGAGCAGCTATAGAAACATTAATGCATGAAAGAGATCTAAATATT

537 TGCAAATTAGTACCATTCGACAGCTGCCACCTGCCCATTGTTTGATTCCACGTGGCACAG

538 TTTGAAGTGAGTAACACCTAGACATGACATTGTACAACTTAAAGAACAATAGAAATTTGC

539 TTTACAGTTGTAGTTGTTTGCACGAATTGTTGAGTAACTTCTTTACTCATTTGAGGGTTT

540 TTGATCTTATGGATCTGACAAACAATGCACTGATTTATTCGTATGAGACCAAAAAATCTC

541 GATGATCCAAGGTATCTCGTCATGTCCTTAAGAGCTTGGTTTCTCTTTCTATCCCAGTTT

542 GCAAATGAACAGCCTGGCAGATTCCTAGTCTGGAATTAGGCAGTAAATAGTTATTTAATT

543 ACATCTAAGTGGTTTTATGTACATATAAGAAACTGGCATGTTTATGAGTGGAACAACTTT

544 CTGTAAAACTTATCTTTGTATATAACAAGATTGAGCATGCCTAGAATAGAAAGAACAATT

545 TTAATCAAATCTGCAGTGTTAACCACCTGTTATCTACATGGGATTCTTACAAGCTATTCT

546 AAGTGGTTATGATTATCCAAAGTTCGTATCCGCAGATTACATGACAGTGTATGCTGCGCA '

547 AAGATGAGATGTAGAGATGGATAAAGTTTGAATATATCTCAAAGCACGGCCTTGAGTTTT

548 AATTAATACCGGTTGAGTTTGTTCGGTTACACAATATATGACTTCATGATTAGCCATTTA

549 AAATGTCGGGTCGCAGAAATCCGCTGTTGAATATCCCAATTCCTGCTCGGCAACAGACTC

550 AGAGCGAGTCTTTTATAACAGGTTATTTTATTGTAAGAAAGCACACTTGTTTATGTGTAA

551 TCCACATGCACGGTCCAGTCCTCAGTGTTCACCCATAAGGACACCCCATGTTTGTTAATG

552 AATGCTCGGACACAGTAAATTAAATTCACTCGAGAATAAGTTCCTCGCCATTCACAATAA

553 CTTAGGCTTGAGCCCTAGATGCTGTACACAGAGCAGAATAATAGTGATGTATTAAGTAAT

554 GGATATCTGAGGTATTGATGTTGTACGATCCTCAGATCTACCTTTGATGCGTTATGCTGA

555 GAACTATGCTTTAACCTCTTTCAAATGTGTTTGTCAAATGCTTTCATAGCTTTATATATT

556 ATCATAATAGACATTCAAGTGATGACACCCTATGGTAAAACAATGGTTTCCAGATTCCAT

TABLE 4; Cell signaling oligonucleotide sequences (continued)

SEQ ID NO Sequence

557 AAATAAAGTATAGAATATTACAGTATGTCCACTCACTCTTCCAGGGTTTCCCCGATGGAT

558 TATGGTTCAGTATCAAGCCCAAAAGGGACAACAACCATGCAGTCCCTCTGTACTGTAAGA

559 CAGTGTAGAGCATCTTCAGGCACAAGGACTACAGTATTACGGCGGATGATCAGTATAGCT

560 CAAAAAGTTTTGGAGTAATTGAGTAAATTATCCAATATGGTATTTGACCTCCTAAACAAA

561 GTTTTCTCAAAGTCGTAATAAATTTGTTTAGAAATTGTTGTACTGTTAATGCCCAACCGG

562 CATTTTATCAATTAGAAGGACAACTTTTATGAAAGCAGGATAATTCTAGGTGTAGTGCTA

563 TTTTCAAGTTTTTAAGACAGTTAAATACTCCTATCCTGTGGTGTCTGGATAAACATACCA

564 TGTGTAATCCATTAGCAAGGTCCTTGACAGCATTTTAAGCTGTAAGTTTAGAAGGTTTCA

565 TATGCTTGAATTTAAGTAGATTGGAGCTGTGAGACAGATGATTATATTCTCGACTTTTCT

566 TTTATTCATTTTAGTGAGTGGAAGGAGAGGACATTTTTATGGGTCTGCCACAGAAATTGA

567 TGAACAAGCACCAAAGTTTGGTAGTTGGAAAGACTAAATGAAATCATTATGAGTATATTC

568 CATTTGCATATTTAGAGGATATTCAAATGAGATTTATGAAGACATATGGCCGTGTGGCTC

569 ATGTTCCATGCCTAACAGGTATTGAGATTCAGGTCTATGTAGTAGTTTATCGTATACATC

570 GCTGCAGATAAGTCCCTTTACATTAAATGATTGGAAATTCTATACCCGGCTAAATGTTGT

571 TATTTTCAGGGAAAATGTCGCCTGCGGAGTCTTCTCGTGAAGAAAGTGTGTATATGGCCA

572 TTTATGTACTTTGAGTGTCTGACTAGAGAAGCATCATCGCTAGAATTAAGGAGGATGCCT

573 AATTTTTCGTTATTCAATGCATGTTTTCTCCTTACAGGAATTGCGAGCCTCTCGAGTCTT

574 AATCTCATCCAGCCGTTCTCACATCAAATCTTGCGAACTCGGAAATTAGCGTTCAATATA

575 TGCCATGTGTTTAAGATTTCCGCATGTATACCGGCACTATTAACATATGCAAGTATTCAT

576 TAATTTCTATACGTAGTACGTTTTTGAGATTTTGTGTGTTATAAAGCCACATGTTATGCT

577 GATGTTTCCGTATGCATTTATTGTCTCGGAAGTCTTGTTATTTCTAGGCTTTTGTTCTTC

578 TATGGACTTACTCGCAAGCAGCTCGACCGTGATATCTGGGTATAACTAACTAGCTATAAA

579 TCTAGAGAACTATTCAAGGTATTTGAGTGGAAACTATAACTATAAGATAGCTGTAGGTGT

580 CTGTAAATATAGATTTGTGGTGGCACGAAGAGGCTTCGAATAATGTGACCTTCATGTTTT 581 GGATATTACTATCTCAAATTGTCGGTTCCCGTGTGCGCTCTTTCGTGCTGCCTAGTTTAA 582 CTTTTGTCACCATTCTTGTATGACTTGTAAACAGTACGCAGATTCGATATCCTATTCGGC 583 TGTATATTACGCAGAGGATTTGTCCATCTATAACATGATCGTCGATCGTCACTACTTTAC

TABLE 7 Nucleotide Sequence of the DNA Construct pWVR202

SEQ ID NO Sequence

584 CGCCGGCGTTGTGGATACCTCGCGGAAAACTTGGCCCTCACTGACAGATGAGGGGCGGAC

GTTGACACTTGAGGGGCCGACTCACCCGGCGCGGCGTTGACAGATGAGGGGCAGGCT CG

ATTTCGGCCGGCGACGTGGAGCTGGCCAGCCTCGCAAATCGGCGAAAACGCCTGATT TTA

CGCGAGTTTCCCACAGATGATGTGGACAAGCCTGGGGATAAGTGCCCTGCGGTATTG ACAC

TTGAGGGGCGCGACTACTGACAGATGAGGGGCGCGATCCTTGACACTTGAGGGGCAG AGT

GCTGACAGATGAGGGGCGCACCTATTGACATTTGAGGGGCTGTCCACAGGCAGAAAA TCCA

GCATTTGCAAGGGTTTCCGCCCGTTTTTCGGCCACCGCTAACCTGTCTTTTAACCTG CTTTT

AAACCAATATTTATAAACCTTGTTTTTAACCAGGGCTGCGCCCTGTGCGCGTGACCG CGCAC

GCCGAAGGGGGGTGCCCCCCCTTCTCGAACCCTCCCGGCCCGCTAACGCGGGCCTCC CA

TCCCCCCAGGGGCTGCGCGCCTCGGCCGCGAACGGCCTCACCCCAAAAATGGCAGCG CT

GGCAGTCCATAATTGTGGTTTCAAAATCGGCTCCGTCGATACTATGTTATACGCCAA CTTTG

AAAACAACTTTGAAAAAGCTGTTTTCTGGTATTTAAGGTTTTAGAATGCAAGGAACA GTGAAT

TGGAGTTCGTCTTGTTATAATTAGCTTCTTGGGGTATCTTTAAATACTGTAGAAAAG AGGAAG

GAAATAATAAATGGCTAAAATGAGAATATCACCGGAATTGAAAAAACTGATCGAAAA ATACC

GCTGCGTAAAAGATACGGAAGGAATGTCTCCTGCTAAGGTATATAAGCTGGTGGGAG AAAA

TGAAAACCTATATTTAAAAATGACGGACAGCCGGTATAAAGGGACCACCTATGATGT GGAAC

GGGAAAAGGACATGATGCTATGGCTGGAAGGAAAGCTGCCTGTTCCAAAGGTCCTGC ACTT

TGAACGGCATGATGGCTGGAGCAATCTGCTCATGAGTGAGGCCGATGGCGTCCTTTG CTCG

GAAGAGTATGAAGATGAACAAAGCCCTGAAAAGATTATCGAGCTGTATGCGGAGTGC ATCA

GGCTCTTTCACTCCATCGACATATCGGATTGTCCCTATACGAATAGCTTAGACAGCC GCTTA

GCCGAATTGGATTACTTACTGAATAACGATCTGGCCGATGTGGATTGCGAAAACTGG GAAG

AAGACACTCCATTTAAAGATCCGCGCGAGCTGTATGATTTTTTAAAGACGGAAAAGC CCGAA

GAGGAACTTGTCTTTTCCCACGGCGACCTGGGAGACAGCAACATCTTTGTGAAAGAT GGCA

AAGTAAGTGGCTTTATTGATCTTGGGAGAAGCGGCAGGGCGGACAAGTGGTATGACA TTGC

CTTCTGCGTCCGGTCGATCAGGGAGGATATCGGGGAAGAACAGTATGTCGAGCTATT TTTT

GACTTACTGGGGATCAAGCCTGATTGGGAGAAAATAAAATATTATATTTTACTGGAT GAATTG

TTTTAGTACCTAGATGTGGCGCAACGATGCCGGCGACAAGCAGGAGCGCACCGACTT CTTC

CGCATCAAGTGTTTTGGCTCTCAGGCCGAGGCCCACGGCAAGTATTTGGGCAAGGGG TCG

CTGGTATTCGTGCAGGGCAAGATTCGGAATACCAAGTACGAGAAGGACGGCCAGACG GTC

TACGGGACCGACTTCATTGCCGATAAGGTGGATTATCTGGACACCAAGGCACCAGGC GGGT

CAAATCAGGAATAAGGGCACATTGCCCCGGCGTGAGTCGGGGCAATCCCGCAAGGAG GGT

GAATGAATCGGACGTTTGACCGGAAGGCATACAGGCMGAACTGATCGACGCGGGGTT TTC

CGCCGAGGATGCCGAAACCATCGCAAGCCGCACCGTCATGCGTGCGCCCCGCGAAAC CTT

CCAGTCCGTCGGCTCGATGGTCCAGCAAGCTACGGCCAAGATCGAGCGCGACAGCGT GCA

ACTGGCTCCCCCTGCCCTGCCCGCGCCATCGGCCGCCGTGGAGCGTTCGCGTCGTCT CGA

ACAGGAGGCGGCAGGTTTGGCGAAGTCGATGACCATCGACACGCGAGGAACTATGAC GAC

CAAGAAGCGAAAAACCGCCGGCGAGGACCTGGCAAAACAGGTCAGCGAGGCCAAGCA GG

CCGCGTTGCTGAAACACACGAAGCAGCAGATCAAGGAAATGCAGCTTTCCTTGTTCG ATATT

GCGCCGTGGCCGGACACGATGCGAGCGATGCCAAACGACACGGCCCGCTCTGCCCTG TTC

ACCACGCGCAACAAGAAAATCCCGCGCGAGGCGCTGCAAAACAAGGTCATTTTCCAC GTCA

ACAAGGACGTGAAGATCACCTACACCGGCGTCGAGCTGCGGGCCGACGATGACGAAC TGG

TGTGGCAGCAGGTGTTGGAGTACGCGAAGCGCACCCCTATCGGCGAGCCGATCACCT TCA

CGTTCTACGAGCTTTGCCAGGACCTGGGCTGGTCGATCAATGGCCGGTATTACACGA AGGC

CGAGGAATGCCTGTCGCGCCTACAGGCGACGGCGATGGGCTTCACGTCCGACCGCGT TGG

GCACCTGGAATCGGTGTCGCTGCTGCACCGCTTCCGCGTCCTGGACCGTGGCAAGAA AAC

GTCCCGTTGCCAGGTCCTGATCGACGAGGAAATCGTCGTGCTGTTTGCTGGCGACCA CTAC

ACGAAATTCATATGGGAGAAGTACCGCAAGCTGTCGCCGACGGCCCGACGGATGTTC GACT

ATTTCAGCTCGCACCGGGAGCCGTACCCGCTCAAGCTGGAAACCTTCCGCCTCA

TGTGCGGATCGGATTCCACCCGCGTGAAGAAGTGGCGCGAGCAGGTCGGCGAAGCCT GC

GAAGAGTTGCGAGGCAGCGGCCTGGTGGAACACGCCTGGGTCAATGATGACCTGGTG CAT

TGCAAACGCTAGGGCCTTGTGGGGTCAGTTCCGGCTGGGGGTTCAGCAGCCAGCGCT TTA

CAAAGGAGTCTAGAAGATCCTGGCATTTCAGGAACAAGCGGGCACTGCTCGACGCAC TTGC TTCGCTCAGTATCGCTCGGGACGCACGGCGCGCTCTACGAACTGCCGATAGACAACTGTC A CGGTTAAGCGAGAAATGAATAAGAAGGCTGATAATTCGGATCTCTGCGAGGGAGATGATA T

TABLE T Nucleotide Sequence of the DNA Construct pWVR202 (continued)

SEQ ID NO Sequence

TTGATCACAGGCAGCAACGCTCTGTCATCGTTACAATCAACATGCTACCCTCCGCGA GATCA

TCCGTGTTTCAAACCCGGCAGCTTAGTTGCCGTTCTTCCGAATAGCATCGGTAACAT GAGCA

AAGTCTGCCGCCTTACAACGGCTCTCCCGCTGACGCCGTCCCGGACTGATGGGCTGC CTG

TATCGAGTGGTGATTTTGTGCCGAGCTGCCGGTCGGGGAGCTGTTGGCTGGCTGGTG GCA

GGATATATTGTGGTGTAMCAAATTGACGCTTAGACMCTTAATAACACATTGCGGACG TTTT

TMTGTACTGGGGTGGTTTTTCTTTTCACCAGTGAGACGGGCMCAGCTGATTGCCCTT CAC

CGCCTGGCCCTGAGAGAGTTGCAGCAAGCGGTCCACGCTGGTTTGCCCCAGCAGGCG AM

ATCCTGTTTGATGGTGGTTCCGAMTCGGCAAMTCCCTTATAMTCAAAAGMTAGCCCG A

GATAGGGTTGAGTGTTGTTCCAGTTTGGMCMGAGTCCACTATTAMGMCGTGGACTCC A

ACGTCAMGGGCGMAMCCGTCTATCAGGGCGATGGCCCACGGCCGCTCTAGAACTAGT

GGATCCCCCCTACGTGCGATCTAGTAACATAGATGACACCGCGCGCGATMTTTATCC TAGT

TTGCGCGCTATATTTTGTTTTCTATCGCGTATTAMTGTATMTTGCGGGACTCTMTCA TM

MACCCATCTCATAMTAACGTCATGCATTACATGTTMTTATTACATGCTTMCGTMTTC AA

CAGAAATTATATGATAATCATCGCMGACCGGCAACAGGATTCAATCTTMGAMCTTTA TTG

CCAMTGTTTGMCGATCCCTCAGMGAACTCGTCAAGMGGCGATAGMGGCGATGCGCT

GCGAATCGGGAGCGGCGATACCGTAAAGCACGAGGAAGCGGTCAGCCCATTCGCCGC CM

GCTCTTCAGCAATATCACGGGTAGCCMCGCTATGTCCTGATAGCGGTCCGCCACACC CAG

CCGGCCACAGTCGATGAATCCAGMAAGCGGCCATTTTCCACCATGATATTCGGCMGC AG

GCATCGCCATGGGTCACGACGAGATCCTCGCCGTCGGGCATGCGCGCCTTGAGCCTG GCG

MCAGTTCGGCTGGCGCGAGCCCCTGATGCTCTTCGTCCAGATCATCCTGATCGACMG AC

CGGCTTCCATCCGAGTACGTGCTCGCTCGATGCGATGTTTCGCTTGGTGGTCGAATG GGCA

GGTAGCCGGATCAAGCGTATGCAGCCGCCGCATTGCATCAGCCATGATGGATACTTT CTCG

GCAGGAGCAAGGTGAGATGACAGGAGATCCTGCCCCGGCACTTCGCCCMTAGCAGCC AG

TCCCTTCCCGCTTCAGTGACAACGTCGAGCACAGCTGCGCAAGGMCGCCCGTCGTGG CC

AGCCACGATAGCCGCGCTGCCTCGTCCTGGAGTTCATTCAGGGCACCGGACAGGTCG GTC

TTGACAAAMGMCCGGGCGCCCCTGCGCTGACAGCCGGMCACGGCGGCATCAGAGCAG

CCGATTGTCTGTTGTGCCCAGTCATAGCCGAATAGCCTCTCCACCCMGCGGCCGGAG MC

CTGCGTGCMTCCATCTTGTTCMTCATCTGTTAATCAGAAAAACTCAGATTMTCGACA MT

TCGATCGCACAMCTAGAAACTAACACCAGATCTAGATAGAAATCACAMTCGAAGAGT AAT

TATTCGACAAAACTCAMTTATTTGMCAMTCGGATGATATTTATGAMCCCTMTCGAGA A

TTMGATGATATCTMCGATCAMCCCAGAAMTCGTCTTCGATCTMGATTAACAGMTCTA

AACCAMGAACATATACGAMTTGGGATCGMCGAAMCAAMTCGMGATTTTGAGAGAAT

AAGGAACACAGAMTTTACCTTGATCACGGTAGAGAGAATTGAGAGAAAGTTTTTMGA TTTT

GAGMATTGAMTCTGMTTGTGMGMGAAGAGCTCTTTGGGTATTGTTTTATAGMGMG

MGMGMMGACGAGGACGACTAGGTCACGAGAMGCTMGGCGGTGMGCMTAGCTAA

TAATAAAATGACACGTGTATTGAGCGTTGTTTACACGCMAGTTGTTTTTGGCTAATT GCCTT

ATTTTTAGGTTGAGGAAAAGTATTTGTGCTTTGAGTTGATAMCACGACTCGTGTGTG CCGG

CTGCMCCACTTTGACGCCGTTTATTACTGACTCGTCGACMCCACMTTTCTAACGGTC GT

CATAAGATCCAGCCGTTGAGATTTMCGATCGTTACGATTTATATTTTTTTAGCATTA TCGTTT

TATTTTTTAMTATACGGTGGAGCTGAAMTTGGCMTMTTGMCCGTGGGTCCCACTGCA

TTGMGCGTATTTCGTATTTTCTAGMTTCTTCGTGCTTTATTTCTTTTCCTTTTTGTT TTTTTT

TGCCATTTATCTMTGCAAGTGGGCTTATAMATCAGTGMTTTCTTGGAMAGTMCTTCT T

TATCGTATMCATATTGTGMATTATCCATTTCTTTTMTTTTTTAGTGTTATTGGATAT TTTTG

TATGATTATTGATTTGCATAGGATMTGACTTTTGTATCMGTTGGTGMCMGTCTCGTT M

MMGGCMGTGGTTTGGTGACTCGATTTATTCTTGTTATTTMTTCATATATCAATGGAT CTT

ATTTGGGGCCTGGTCCATATTTAACACTCGTGTTCAGTCCAATGACCAATMTATTTT TTCAT

TAATAACMTGTMCMGMTGATACACAAMCATTCTTTGMTAAGTTCGCTATGMGMGG

GAACTTATCCGGTCCTAGATCATCAGTTCATACAAACCTCCATAGAGTTCMCATCTT AMCA

AGGATATCCTGATCCGTTGACGGCGCGCCMGCGGCCGCAAMCCCCTCACAMTACATM

MAAAATTCTTTATTTAATTATCAMCTCTCCACTACCTTTCCCACCMCCGTTACAATC CTGA

ATGTTGGAAAAAACTAACTACATTGATATAAAAAAACTACATTACTTCCTAMTCATA TCAAM

TTGTATAMTATATCCACTCACTTGGACAMTTGCCCATAGTTGGAMGATGTTCACCAA GTC

MCAAGATTTATCAATGGAAMATCCATCTACCAAACTTACTTTCMGAAAATCCMGGAT TA

TAGAGTAAAAAATCTATGTATTATTMGTCAAMAGAAMCCAMGTGMCMATATTGATGT

ACMGTTTGAGAGGATMGACATTGGMTCGTCTAACCAGGAGGCGGAGGMTTCCCTAGA

CAGTTAMAGTGGCCGGMTCCCGGTAAAAMGATTAAMTTTTTTTGTAGAGGGAGTGCT T

GMTCATGTTTTTTATGATGGAAATAGATTCAGCACCATCAAAAACATTCAGGACACC TAAM

TABLE 7: Nucleotide Sequence of the DNA Construct pWVR202 (continued)

SEQ ID NO Sequence

TTTTGAAGTTTAACAAAAATAACTTGGATCTACAAAAATCCGTATCGGATTTTCTCT AAATATA

ACTAGAATTTTCATAACTTTCAAAGCAACTCCTCCCCTAACCGTAAAACTTTTCCTA CTTCAC

CGTTAATTACATTCCTTAAGAGTAGATAAAGAAATAAAGTAAATAAAAGTATTCACA AACCAA

CAATTTATTTCTTTTATTTACTTAAAAAAACAAAAAGTTTATTTATTTTACTTAAAT GGCATAAT

GACATATCGGAGATCCCTCGAACGAGAATCTTTTATCTCCCTGGTTTTGTATTAAAA AGTAAT

TTATTGTGGGGTCCACGCGGAGTTGGAATCCTACAGACGCGCTTTACATACGTCTCG AGAA

GCGTGACGGATGTGCGACCGGATGACCCTGTATAACCCACCGACACAGCCAGCGCAC AGT

ATACACGTGTCATTTCTCTATTGGAAAATGTCGTTGTTATCCCCGCTGGTACGCAAC CACCG

ATGGTGACAGGTCGTCTGTTGTCGTGTCGCGTAGCGGGAGAAGGGTCTCATCCAACG CTAT

TAAATACTCGCCTTCACCGCGTTACTTCTCATCTTTTCTCTTGCGTTGTATAATCAG TGCGAT

ATTCTCAGAGAGCTTTTCATTCAAAGGTATGGAGTTTTGAAGGGCTTTACTCTTAAC ATTTGT

TTTTCTTTGTAAATTGTTAATGGTGGTTTCTGTGGGGGAAGAATCTTTTGCCAGGTC CTTTTG

GGTTTCGCATGTTTATTTGGGTTATTTTTCTCGACTATGGCTGACATTACTAGGGCT TTCGTG

CTTTCATCTGTGTTTTCTTCCCTTAATAGGTCTGTCTCTCTGGAATATTTAATTTTC GTATGTA

AGTTATGAGTAGTCGCTGTTTGTAATAGGCTCTTGTCTGTAAAGGTTTCAGCAGGTG TTTGC

GTTTTATTGCGTCATGTGTTTCAGAAGGCCTTTGCAGATTATTGCGTTGTACTTTAA TATTTT

GTCTCCAACCTTGTTATAGTTTCCCTCCTTTGATCTCACAGGAACCCTTTCTTCTTT GAGCAT

TTTCTTGTGGCGTTCTGTAGTAATATTTTAATTTTGGGCCCGGGTTCTGAGGGTAGG TGATT

ATTCACAGTGATGTGCTTTCCCTATAAGGTCCTCTATGTGTAAGCTGTTAGGGTTTG TGCGT

TACTATTGACATGTCACATGTCACATATTTTCTTCCTCTTATCCTTCGAACTGATGG TTCTTTT

TCTAATTCGTGGATTGCTGGTGCCATATTTTATTTCTATTGCAACTGTATTTTAGGG TGTCTC

TTTCTTTTTGATTTCTTGTTAATATTTGTGTTCAGGTTGTAACTATGGGTTGCTAGG GTGTCTG

CCCTCTTCTTTTGTGCTTCTTTCGCAGAATCTGTCCGTTGGTCTGTATTTGGGTGAT GAATTA

TTTATTCCTTGAAGTATCTGTCTAATTAGCTTGTGATGATGTGCAGGTATATTCGTT AGTCAT

ATTTCAATTTCAAGCGATCCCCCGGGCTGCAGGCTAGCTAAAAGTACTTTTCCTAGG ATCGA

TGGGTGTTATTTGTGGATAATAAATTCGGGTGATGTTCAGTGTTTGTCGTATTTCTC ACGAAT

AAATTGTGTTTATGTATGTGTTAGTGTTGTTTGTCTGTTTCAGACCCTCTTATGTTA TATTTTT

CTTTTCGTCGGTCAGTTGAAGCCAATACTGGTGTCCTGGCCGGCACTGCAATACCAT TTCGT

TTAATATAAAGACTCTGTTATCCGTGAGCTCGAATTTCCCCGATCGTTCAAACATTT GGCAAT

AAAGTTTCTTAAGATTGAATCCTGTTGCCGGTCTTGCGATGATTATCATATAATTTC TGTTGA

ATTACGTTAAGCATGTAATAATTAACATGTAATGCATGACGTTATTTATGAGATGGG TTTTTAT

GATTAGAGTCCCGCAATTATACATTTAATACGCGATAGAAAACAAAATATAGCGCGC AAACT

AGGATAAATTATCGCGCGCGGTGTCATCTATGTTACTAGATCGCGGCCGCATTTAAA TGGG

CCCTGTTAACTGGTACCTTAATTAAAAGTTTAAACTATCAGTGTTTGACAGGATATA TTGGCG

GGTAAACCTAAGAGAAAAGAGCGTTTATTAGAATAATCGGATATTTAAAAGGGCGTG AAAAG

GTTTATCCGTTCGTCCATTTGTATGTGCATGCCAACCACAGGGTTCCCCAGATC

AHy. Dkt. No. 044463-0530

U(

O

WASH 1631515.1

Atty. Dkt. No. 044463-0530

o NT = not tested - No effect observed