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)
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)
US6867350B2 |
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 |
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
[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).
[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
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