Background Information The use of mass spectrometers, including those which perform tandem mass spectrometry (MS/MS), are known to be useful in determining amino acid sequences. Currently available spectrometers are capable of presenting a wide mass range of ions, MS/MS providing daughter ion analysis of a single parent mass. The parent ion is selected by use of a frequency of applied supplemental voltage and the daughter ions are ejected by scanning. From this it is possible to obtain a reconstructed parent ion spectrum from a large number of successive daughter ion scans.

Parent ions may also be excited by pulses of energy at their resonant frequency, the daughter ions may be ejected from the ion trap at their resonant frequency.

The available means for determining unique amino acid sequence lacks specificity.

Ion trap mass spectrometers, such as those manufactured by the Finnigan Corporation, employ an electrostatic field in which ions are formed and stored by use of a quadrupole trapping field. In a tandem

quadrupole ion trap mass spectrometer, ions are formed and stored in an ion trap and then mass selected by a mass analyzer wherein the ions are dissociated by means of a collision induced dissociation with a gas or surface and the fragment ions are analyzed by means of a mass or energy analyzer. During the operation of a tandem quadrupole ion trap mass spectrometer product ions, or daughter ions, are produced by isolating a precursor ion, or parent ion, which has undergone the collision induced dissociation. The collision induced dissociation can occur by applying an excitation waveform between end cap electrodes. A radio frequency voltage generator can be used to supply an RF voltage between the end caps and a ring electrode which provides the quadrupole field for trapping ions. A supplemental RF generator is coupled to the end caps to resonate trapped ions at their axial resonant frequencies. These excited ions undergo fragmentation upon the colliding with a surface or buffer gas, such as helium, placed within the buffer trap. An end cap is perforated to allow unstable ions in the field of the ion trap to exit and be detected by an electron multiplier. The magnitude and/or frequency of the fundamental RF voltage can be varied for providing mass selection. The goal is to isolate a particular ion.

Commercially available quadrupole ion trap mass spectrometers capable of tandem mass spectrophotometry are capable of isolating a single parent ion by inducing

a collision dissociation to produce daughter ions which are resonantly ejected from an ion trap for detection by a mass-selective instability scan.

Alternative techniques that should also be noted include the application of simultaneous excitation voltages or waveforms across the end caps.

After any characteristic daughter ions in the trap have been ejected, application of a parent ion resonant excitation waveform, can result in some parent ions that are resonantly ejected resulting in false positive readings during the detection of the characteristic daughter ions.

Sample mass may be analyzed by any combination of ionization and mass spectrometer. The ionization method may include, but is not limited to such methods as electron ionization, chemical ionization, fast atom bombardment, desorption chemical ionization, plasmadeorption, thermospray, atmospheric pressure chemical ionization, MALDI or electrospray ionization (ESI). Principally the ionization method will be MALDI or ESI. Prior art mass spectrometer formats are known to be useful either singly or in various combinations for use in analyzing translation products. These formats may include, but are not limited to, ionization (I) techniques, including but not limited to matrix assisted laser desorption (MALDI), continuous or pulsed electrospray (ESI) and related methods (e. g. , IONSPRAY or

THERMOSPRAY), or massive cluster impact (MCI); these ion sources can be matched with detection formats including linear or non-linear reflection time-of-flight (TOF), single or multiple quadropole, single or multiple magnetic sector, Fourier Transform ion cyclotron resonance (FTICR), ion trap, and combinations thereof (e. g. , ion-trap/time-of-flight). For ionization, numerous matrix/wavelength combinations (MALDI) or solvent combinations (ESI) can be employed.

With regard to the mass spectrometer, per se, there are several types of tandem mass spectrometers that could be used to generate the patterns of MS/MS spectra that are the substrate for the program. These mass spectrometers generate both parent ions in the +1 (MALDI and ESI) and the +2, +3, +4 etc charge state (ESI). The program takes the charge state of the parent into consideration as part of the data associated with the parent ion. The types of mass analyzer mass analyzers include the quadropole, octopole, ion trap or QUISTOR, time of flight (TOF) Time of Flight with reflectron, the Fourier transformed ion cyclotron resonance (FTICR also called FTMS), magnetic and electromagnetic sector.

The tandem mass spectrometer mass consist of the homogenous or heterogenous combination of two or more of any of these devices in any order (Hybrid instrument).

The fragmentation method may include post source decay of the parent ion or its fragment, or collision-activated or

collision-induced decomposition of the parent ions, or fragment ions, or metastable ions with a relatively immobile target such as gas molecules or other parent or fragment ions, or photons or electrons or solid objects.

The combinations may preferentially include the quadropole or octopole ion trap, the Quadropole-Quadropole (DC and rf or rf only) -TOF, the ion trap-FTMS, the TOF-TOF, the ion trap-TOF, or the TOF-PSD-TOF. The signal resulting from the instrument may be mathematically transformed or filtered.

In view of this, sequence determination of an unknown protein or peptide from mass spectral data can be difficult due to the voluminous number of possible sequences consistent with the molecular weight of the amino acid. Multiple samples result in readings that are unacceptable for most applications due to offsets in samples, preparations, device manufacture, noise filtration, technician sample handling, and so forth.

Further, recent advancements in amino acid synthesis have allowed the generation of millions of peptide and protein sequences.

Thus, what is needed in the art is a method of analyzing the voluminous amounts of data that is being produced by such devices.

SUMMARY OF THE INVENTION The present invention satisfies this need through a method of determining unique amino acid sequences between two groups of samples as analyzed by mass spectrometer, such as a quadrupole ion trap. MS data from multiple samples is received from an MS ion trap, the data being normalized and may include noise reduction. MS data (dta) is provided in an ASCII format. The data may include noise reduction of the MS as a filter setting forth data files (dta). The Raw data is placed into an Inner-sample pattern match performed by merging same ions to form a first group (patient) and a second group (control). Each group is then pattern matched pairwise by merging ions with the same pattern between two samples taken from each group, to form an inter-group pattern match. The pattern provides a first group of unique ions, a second group of unique ions, and a third group having common ions between the first and second group.

This is used to create data directories for use with the data files. The software bundled with the MS unit, such as SEQUEST, can then be used for word matching. In this manner an Inter-group comparison is performed for protein matching (multiple ions) and peptide matching (single ions).

In operation, samples are first prepared wherein daughter ions ejected having a particular Dalton range for each DTA sample are merged and the DTA's represented

by a single charge state. Parent ions are also merged by scan numbers and the differences of each parent ion mass drop thereby creating a working file for each of the samples which contain data of all DTA's.

Each working file is queried to obtain the parent mass (Mqi) and charge state (Cqi) for each parent ion (Qi) and a target working file is then queried to obtain target DTA list (T1-Tm) having a parent mass (Mtl-Mtm) drop in the range of Mqi 1. 5 Dalton and where their charge states (Ctl-Ctm) is the same as Cqi.

The parent ion is compared with each of the daughter patterns, the daughter ions that match are removed and the use of a scoring system is used to record each match.

The scoring system provides a cumulative score; Qratio (matched/Total_Query ratio); T_ratio (matched/Total Target ratio) and t_score (3* ((Q_ratio + T ratio)/2) *Rs) where Rs is the acceptable ratio (in %) of matched over total.

The common ions (samplel2_common) having matched candidates between Qi and Tj are recorded, and unmatched candidates are separated into separate files (samplel unique) and (sample2_unique), the samples are compared to obtain pair matches of parent mass and charge state. The matches are then clustered and the daughter ion patterns are compared within each of the clusters, calculating the ratio of the matched sample #/Total sample # (Rc) wherein the ion will be included in a final group-common list if

Rc > Rm.

A single file can then be constructed naming Groupx whole (uniques + commons) for each file which contains DTA names (s), parent mass, charge state, and all daughter ions. DTA directories are then constructed based on the above files to recover all the DTAs with different charge states, recover original data format for each DTA, recover original file name for each DTA, and create supporting files for a SEQUEST or similar type search for further filtering. Groups can then be summarized on protein names to generate files: a. Groupluniquewith name, b. Group2 unique with name, c. Groupl unique without-name, d. Group2 unique without name ; wherein Groupuniquewithoutname list is used for optional databases searches, and Group__ : unique-with-name list is used directly for further analysis such as data mining.

An objective of the invention is to provide a method of finding unique protein species between groups of samples provided through mass spectrometry.

Another objective of the invention is to disclose an algorithm for subtracting of common ions between ion samples providing a base for optional database searches for use in further analysis.

Another objective of the invention is to teach the use of ion subtraction between two samples by taking advantage of daughter ion pattern in MS2 spectrum and scan numbers for parent ions.

Still another objective of the invention is to teach the use of ion subtraction with multiple filters in sequence.

Still another objective of the invention is to disclose the use of a scoring system and/or matching ratio for locating of common ions.

Another objective of the invention is to disclose the use of a word-matcher.

Other objectives and advantages of this invention will become apparent from the following description taken in conjunction with the accompanying drawings wherein are set forth, by way of illustration and example, certain embodiments of this invention. The drawings constitute a part of this specification and include exemplary embodiments of the present invention and illustrate various objects and features thereof.

BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is a flow chart for the pattern matcher program of the instant invention; Figure 1A is a continuation of the flow chart of Figure 1; Figure 2 is a flow chart of inner sample pattern matching; Figure 3 is a flow chart of inner group pattern matching; Figure 4 is a flow chart of inter group pattern

matching; Figure 5 is a chart comparing scan numbers versus sequence of the common ions to be MS/MS.

DETAILED DESCRIPTION Referring now in general to the Figures, input data (DTA's) are obtained from a mass spectrometer, such as a Finnigan, or the like MS, that is converted into an ASCII format. The DTA can be obtained from software bundled with the particular MS, such as Sequest, Qstar, Sonar, and so forth. The MS or software may include noise reduction provisions particular to the MS device for normalization of the DTA. The DTA collected include MS spectrum data for a specific ion, or peptide, and in particular the Parent Mass and Charge State, and the daughter ion mass and intensity pairs to form a working file.

For data preparation, daughter peak merging is performed by merging all daughter ions ejected within the range of 0. 3 Dalton. It is well known that the machine reading of the mass of an ion, both parent ions and daughter ions, produces variations. Variations claimed by manufacturers is 0. 3 dalton, however, variations of 1. 5 daltons has been observed in parent masses and variations of 1 daltons has been observed in daughter ion masses. Thus, daughter ions which drop in the same range are considered the same daughter ions as it is very

rare for two different daughter ions from b and y series to have masses so close. A list is created of all daughter ions that are represented by only one charge state wherein the different charge state does not change the daughter composition, and the scan number is the same.

The parent ions in each sample are then merged with adjacent scan number and the differences of the masses of the parent ion drop within the range of about 0.5-1. 0 Dalton. The above principles are used to create a working file for each sample which contains detailed data of all DTA's, including DTA file name and scan number, parent mass and charge state, and a list of the daughter ion masses and intensity pairs.

Daughter ion subtraction takes place between a first query sample (Samplel) compared to a second sample (Target). The working file, previously generated as defined above, is read for each of the parent ions in Query DTA (qi) to obtain parent mass (Mqi) and charge state (Cqi). The Target working file is queried with both Mqi and Cqi, to obtain the target DTA list (T1-Tm) with their parent masses (Mtl-Mtm) drop in the range of Mqi 1. 5 Dalton, and their charge states (Ctl-Ctm) is the same to Cqi: Mtj=Mqi 1. 5 Dalton Ctj=Cqi Where l<_jsm Qi is compared with each of the Tj in T1-Tm list of

daughter patterns. If no match is found, the query MS2 is placed in a unique list. If a match is found, the match is filtered by comparison by a scoring system.

In the scoring system, each daughter ion (Qik) in Qi is compared to the whole list of daughters (Tjl-Tjn) in Tj. It is considered as a match, and Qik and Tjg will be removed from Qi and Tj, respectively, if |Qik-Tjg| si 1 Dalton, where lsgsn The match is awarded a score based on the following scheme (for partition = 4): Score =5, if Qik-Tjg) si 0.25 Dalton; Score =4, if #Qik-Tjg# #~ 0. 50 Dalton; Score =2, if #Qik-Tjg# #~ 0. 75 Dalton; Score =1, if #Qik-Tjg# #~ 1. 00 Dalton.

The comparison will provide the following values: a. S: cumulative score; b. Q_ratio : matched/Total_Query ratio; c. T_ratio : matched/Total_Target ratio; d. t_score = 3* ((Q_ratio + T-ratio)/2) *Rs Rs: acceptable ratio (in%) of matched over total.

The comparison will be considered as a pattern match candidate, to be included into the list of matched candidates QT, if the following conditions are met: a. S > Score ; b. Total_Target > Td and Total_Query > Td; c. 1 s Total_Query or Total_Query/Total_Target s 2.

If the QT list contains a single candidate, then take this candidate as the match and remove Qi and Ti from Query and Target list, respectively.

If the QT list contains more than one match candidates, the list is filtered to find a match by the

following method: a. Calculate DQT: DQT = Medium (Scan_Qi)-Medium (Scan Tj) Note: scan number for a DTA can be a range. b. Compare DQT to Standard DQT between the samples by trend: DQT = ScanQl-ScanTl or DQT = ScanQi-ScanTj.

Where Scan_Qi and Scant are considered the best match between two samples. If DQT > 1 and Dqt < 1, then it is likely that Tj belongs to a different peptide and Tj is to be removed from QT list. c. Compare Dqt to FQT between the sample by distance: FQT = k * ((Scan_Qi + Scan_Tj)/2) Where k is the slope of a linear function Scan_QT=f (dqt) = k * dqt +b. The function of f (dqt) is proximated to linear correlation. d. Choose the Tj with the highest score Sj from remaining QT list to be the final match.

It should be noted that each of the DTA's have a specific scan number, which is the indication when an ion has been out of a column and analyzed by MS/MS. The sequence of a scan number for a sample is fairly stable.

However, the scan numbers shift between sample runs. If there is the same ion in both samples to be compared, scan number of this ion in one of the samples will differ from another sample. The distance of this same ion in two samples is the function of the scan numbers, in the range of 20 (scan number 600) -400 (scan number 4000).

Figure 5 depicts a typical curve drawn with the data from extracted common ions from two samples as discussed in this disclosure.

After all the Query DTAs have been used for comparisons, a consensus file is generated which contains the common ions between the two samples. Files are generated for ions unique to each sample: a. samplel2_common (each matched ions'DTA names, parent masses, charge states, pattern daughters). b. samplelunique ; c : sample2 unique.

5. Within each group, pairing samples in all possible ways to the pairwise comparison as above. The total number of the comparison is given out by: 2 (I-1 I=n Where n is the number of samples with the group.

The samplel2_common files are merged and, and hash all the entries (pair matches) with parent mass + charge state. Cluster all the entries on their parent mass +

charge state, with variation of 1.5 Dalton. So, the members of each clusters are considered the candidates for extended matches outside of the original pairwise matches.

Daughter ion pattern comparison is performed within each of the clusters on the pattern daughter ions. The ratio Rc (the matched sample &num /Total sample #) is then calculated. The ion will be included in the final group common list if: Rc 2 Rm If there is any mismatch within the cluster, then create another cluster to include them. Rc is calculated for each of these sub-clusters, and evaluated as follows: Rc 2 Rm One file is generated for each group: Groupx whole (uniques + commons), which should contain: DTA names (s), parent mass, charge state, all daughter ions.

The scoring system is repeated to compare the 2 final group files. The final files generated are: a. Groupl unique ; b. Group2 unique ; c. Groupl2_common.

The 3 DTA directories are reconstructed based on the above files. The DTA reconstruction should be: a. Recover all the DTAs with different charge

states; b. For each DTA, recover original data format; c. For each DTA, recover original file name; d. Create supporting files for software (e. g.

SEQUEST, QStar) search.

The software bundled with the MS can be further used to compare the peptide sequences among those single ions.

This allows the uncharacterized ions to be reviewed in view of their correlation among those ions tagged with the same peptide sequence. The sequences predicated by the bundled program, such as SEQUEST, is not of interest in this step, rather, the correlations are of interest.

Further, the sequences predicated along with the protein name associated with the sequence provide research assistance.

The SEQUEST Search allows further filtering: However, instead of having M*N number of SEQUEST searches, there are only 3 summary results: a. One for common ones, which is optional, for reference; b. One for Groupl; c. One for Group2.

2. Subtracting Groupl and Group2 summary files on protein names generates files: a. Groupluniquewithname ; b. Group2 unique with name ; c. Groupluniquewithoutname ;

d. Group2uniquewithoutname.

Groupuniquewithoutname list should be used for optional databases searches, e. g. , with 6 reading frame databases.

Group-unique-with-name list can be used directly for further analysis, including data mining.

Example 1. Unique Proteins in control group.

Proteins sharing keywords with the subtracted.

(Format: Protein name and IDs: Keywords) gi|2258128|emb|CAA69 complement 9 [homo sapiens] [mass=60398] : complement C05ADEE16G02. 0791.0793. 2. dta C05ADEE16G02. 2549.2549. 3. dta C05ADEE16G02.2537. 2539.2. dta 0145ADEE17G02. 2909.2909. 2. dta C05ADEE16G02.1803. 1805.2. dta C05ADEE16G02. 1666.1676. 2. dta 0145ADEE17G02. 2064.2074. 2. dta 0154ADEE16G02. 2064.2064. 2. dta C05ADEE16G02. 2062.2064. 2. dta 0154ADEE16G02. 2235. 2239. 2. dta The Rest of the Unique Proteins. gil2230021prflIO4011 : fibrin beta [homo sapiens] [mass=50763] C05ADEE16G02. 2294.2324. 2. dta C05ADEE16G02. 1281.1283. 2. dta C07ADEE16G02. 1281.1284. 2. dta C07ADEE16G02. 1581.1587. 3. dta C07ADEE16G02. 2310.2312. 2. dta 0154ADEE16G02. 2672.2690. 2. dta C05ADEE16G02. 0811.0813. 3. dta C07ADEE16G02. 0811.0813. 3. dta 0145ADEE17G02. 2665.2667. 2. dta 0145ADEE17G02. 1962.1964. 2. dta 0145ADEE17G02. 1217.1223. 3. dta 0145ADEE17G02. 1219.1221. 2. dta C07ADEE16G02. 1219.1221. 2. dta 0154ADEE16G02. 1206.1208. 2. dta 0145ADEE17G02. 1203.1205. 2. dta 0154ADEE16G02. 1721. 1723. 3. dta C07ADEE16G02. 0797.0801. 2. dta C05ADEE16G02. 0807.0809. 2. dta C07ADEE16G02. 1343.1345. 2. dta 0145ADEE17G02. 1012.1014. 2. dta

0154ADEE16G02. 1959. 1961. 2. dta C05ADEE16G02. 1959.1961. 2. dta Summary list, refer above for IDs and DTA files. complement 9 [homo sapiens] [mass=60398] fibrin beta [homo sapiens] [mass=50763] Example 2. Unique single ions in control group.

Unique Single Ions in Control Group, With Multiple Samples Matches For Peptide 2 : ADSQAQLLLSTWGVFTAPGLHLK gi ! 15079348 C05ADEE16G02. 2824. 2832. 3. dta C07ADEE16G02. 2834. 2834. 2. dta 3 : AEMEVQMMKKELDQK gil17563838 C05ADEE16G02. 0916. 0918. 3. dta C07ADEE16G02. 0918. 0920. 3. dta 0145ADEE17G02. 1321. 1323. 3. dta 2 : ALDRHQNSPAPR gil20544433 C07ADEE16G02. 1363. 1363. 2. dta 0154ADEE16G02. 1751. 1753. 2. dta 3 : ALFATSTAGLLRCPR gil21229522 C07ADEE16G02. 0643. 0643. 3. dta C05ADEE16G02. 0647. 0649. 3. dta 0154ADEE16G02. 1033. 1035. 3. dta 2 : ANELIKLVGLEGK gill6080327 0145ADEE17G02. 2463. 2469. 1. dta 0154ADEE16G02. 2468. 2470. 2. dta 2 : APVAGLSGAAGGSTLYSFEAK gil21244270 C05ADEE16G02. 2391. 2391. 3. dta 0145ADEE17G02. 2487. 2487. 2. dta 2 : AQEGPDAEIIGGERSVFYLLMK gil12644073 C05ADEE16G02. 1730. 1732. 3. dta 0145ADEE17G02. 2126. 2128. 3. dta 2 : ASDSVQSALKNR gil15238480 C07ADEE16G02. 1036. 1038. 3. dta C05ADEE16G02. 1038. 1038. 3. dta 2 : ASLTRTPPTASLTR gi ! 18594161 C05ADEE16G02. 1712. 1714. 2. dta C07ADEE16G02. 1720. 1722. 2. dta 3 : CLDSVLGEFAFPDEFVVE gil7522626 C05ADEE16G02. 2296. 2314. 3. dta C07ADEE16G02. 2328. 2358. 3. dta 0154ADEE16G02. 2698. 2700. 3. dta 2 : DALTGHLRTHSVGKPHK gil1911483 C05ADEE16G02. 1837. 1841. 3. dta 0145ADEE17G02. 2230. 2234. 3. dta 2 : DAVKFGRMSK girl1082764 C05ADEE16G02. 1503. 1507. 2. dta 0154ADEE16G02. 1893. 1895. 2. dta C05ADEE16G02. 1893. 1895. 2. dta 2 : DEINSLIGQKNVLFFK gil15896245 C07ADEE16G02. 1465. 1465. 2. dta 0145ADEE17G02. 1849. 1849. 2. dta 2 : DRVLMGPARTGGR gil17554264 C05ADEE16G02. 1255. 1265. 2. dta 0154ADEE16G02. 1651. 1665. 2. dta 2 : DWLFSLKISEVK gil20502693 C07ADEE16G02. 0787. 0793. 2. dta 0145ADEE17G02. 1199. 1199. 2. dta 2 : DYIFGNYIER gill0092579 C05ADEE16G02. 1630. 1632. 2. dta C07ADEE16G02. 1641. 1643. 2. dta 2 : EGTIGDMAILGITESFQVKR gil11493524 C05ADEE16G02. 2136. 2188. 3. dta 0154ADEE16G02. 2562. 2564. 3. dta 2 : EHLVQATPENLQEAR gil10092579 C07ADEE16G02. 0853. 0857. 3. dta C05ADEE16G02. 0864. 0864. 3. dta 2 : EKVLAYK gil19913514 C07ADEE16G02. 1914. 1914. 1. dta 0145ADEE17G02. 2294. 2294. 1. dta 2 : ELINYNAFARDFK gil8250394 C05ADEE16G02. 1877. 1887. 2. dta 0145ADEE17G02. 2274. 2274. 2. dta 2 : EMEVYRVTESLQR gi ! 14249254 0154ADEE16G02. 1979. 1981. 2. dta 0145ADEE17G02. 1984. 1988. 2. dta 2 : EPNNNIGRKH gil17440552 C05ADEE16G02. 1235. 1245. 2. dta C07ADEE16G02. 1239. 1239. 2. dta

2 : FSAEALRCHPR gil29389 C05ADEE16G02. 2003. 2005. 2. dta C07ADEE16G02. 2014. 2016. 2. dta 3 : GALAQAQEVSLGADVGRNPR gil17474963 0145ADEE17G02. 2380. 2380. 2. dta C05ADEE16G02. 2503. 2507. 3. dta C07ADEE16G02. 2523. 2525. 3. dta 2 : GDGTDGVGSMPCGR gil18580732 0154ADEE16G02. 1528. 1528. 2. dta 0145ADEE17G02. 1529. 1531. 2. dta C05ADEE16G02. 1529. 1531. 2. dta 2 : GEVQAMLGQSTEELR gill480096 C05ADEE16G02. 1362. 1384. 2. dta 0154ADEE16G02. 1739. 1739. 2. dta 3 : GHPFLQEECKAPAR gil20550933 C05ADEE16G02. 1024. 1026. 3. dta 0154ADEE16G02. 1030. 1030. 3. dta C07ADEE16G02. 1030. 1030. 3. dta 0145ADEE17G02. 1430. 1435. 3. dta 2 : GLLDQGIPSK gil18375646 C07ADEE16G02. 1157. 1157. 3. dta 0154ADEE16G02. 1552. 1552. 3. dta 2 : GLRKMLDNFDCFGDK gil20380096 0145ADEE17G02. 1241. 1241. 3. dta C05ADEE16G02. 1241. 1241. 3. dta C07ADEE16G02. 1241. 1241. 3. dta 0145ADEE17G02. 1639. 1639. 3. dta 0154ADEE16G02. 1639. 1639. 3. dta C07ADEE16G02. 1639. 1639. 3. dta 2 : GLVLVVGSTGSGKSTSLASMIDHR gi ! 14090413 C07ADEE16G02. 1175. 1181. 3. dta C05ADEE16G02. 1186. 1190. 3. dta 2 : GVAVLHIGGGSEVEVNEK gil17864606 0154ADEE16G02. 1172. 1174. 3. dta C05ADEE16G02. 1172. 1174. 3. dta 0145ADEE17G02. 1173. 1175. 3. dta 2 : GWQVYGLALDSDTAPTLR gil21243805 C05ADEE16G02. 0807. 0809. 3. dta 0154ADEE16G02. 1206. 1208. 3. dta 2 : GWRPYEIHSVTPIDEILNMFK gil8923754 C05ADEE16G02. 1616. 1618. 3. dta C07ADEE16G02. 1635. 1637. 3. dta 2 : HAQEELPPPPPQKKR girl118685 C07ADEE16G02. 0839. 0841. 3. dta C05ADEE16G02. 0848. 0848. 3. dta 2 : HLALGCFGLNR gil16805179 C07ADEE16G02. 0877. 0879. 2. dta C05ADEE16G02. 0884. 0886. 2. dta 2 : HTWSLLKEMAK gil11493656 C05ADEE16G02. 2300. 2306. 1. dta 0154ADEE16G02. 2698. 2700. 2. dta 2 : IARNIYIKVGEDQVFPPK gil20535619 C05ADEE16G02. 2051. 2057. 3. dta C07ADEE16G02. 2062. 2074. 3. dta 2 : ILAITFTKK gi ! 12045098 0154ADEE16G02. 2259. 2265. 2. dta C05ADEE16G02. 2328. 2328. 1. dta 2 : KEGDGKGK gil12843573 C05ADEE16G02. 0920. 0922. 2. dta 0145ADEE17G02. 1327. 1329. 2. dta 0154ADEE16G02. 1327. 1329. 2. dta 4 : LAALSTATTVHHQSQHAVTTCYGR gil20891466 C05ADEE16G02. 2401. 2423. 2. dta C07ADEE16G02. 2423. 2439. 3. dta 0145ADEE17G02. 2761. 2763. 3. dta 0145ADEE17G02. 2783. 2783. 2. dta 2 : LAGRILGMGDVASLAEK gil3024639 C05ADEE16G02. 2393. 2397. 2. dta 0154ADEE16G02. 2778. 2784. 2. dta 2 : LAPPPVAELR gil3915680 C07ADEE16G02. 0970. 0976. 2. dta 0154ADEE16G02. 1374. 1376. 2. dta 2 : LLWLVLQPFFYSLR gi ! 18583655 C05ADEE16G02. 2017. 2019. 3. dta 0145ADEE17G02. 2400. 2404. 3. dta 2 : LNNGEITQHR gil29565 C07ADEE16G02. 0580. 0583. 2. dta C05ADEE16G02. 0584. 0586. 2. dta 2 : LRGEAAAGAAGMKR gil17939383 C07ADEE16G02. 0680. 0680. 2. dta 0154ADEE16G02. 1081. 1081. 2. dta

2 : LSSLTPCPN gil8922394 0154ADEE16G02. 1107. 1109. 2. dta 0145ADEE17G02. 1108. 1108. 2. dta 3 : LSWLEGGVR gil15643398 C07ADEE16G02. 0783. 0783. 2. dta C05ADEE16G02. 0784. 0789. 2. dta 0154ADEE16G02. 1186. 1196. 2. dta 2 : MGGAAWDGEKLSVGSGK gi ! 20473307 C05ADEE16G02. 1047. 1066. 3. dta 0154ADEE16G02. 1452. 1456. 3. dta 2 : MGPTTSPVPR gil20541193 0145ADEE17G02. 1261. 1263. 2. dta C05ADEE16G02. 1261. 1263. 2. dta C07ADEE16G02. 1265. 1267. 2. dta 2 : MLAPSGSSGVWR girl6912282 C05ADEE16G02. 0518. 0520. 2. dta 0154ADEE16G02. 0898. 0900. 2. dta 2 : MQLVDHRGGGGGGGKGGR gill3787204 0145ADEE17G02. 1024. 1024. 3. dta 0154ADEE16G02. 1024. 1024. 3. dta C07ADEE16G02. 1024. 1024. 3. dta 0154ADEE16G02. 1421. 1421. 3. dta 2 : NGWLNLEFENR gil20541427 C07ADEE16G02. 2062. 2074. 2. dta 0154ADEE16G02. 2434. 2436. 2. dta 2 : NPIVLSMYFTKQLYR gi) 14733277 C05ADEE16G02. 1146. 1146. 2. dta 0145ADEE17G02. 1537. 1537. 2. dta 2 : NYADQISRLEERESEMK gi ! 10432429 C05ADEE16G02. 1446. 1450. 3. dta C07ADEE16G02. 1455. 1457. 3. dta 2 : PERVLIIGGGDGGVVR gil10945607 C05ADEE16G02. 1078. 1078. 3. dta C07ADEE16G02. 1092. 1092. 3. dta 2 : PIENRILILPSVTR girl1071965 C07ADEE16G02. 0735. 0737. 3. dta 0145ADEE17G02. 1137. 1143. 3. dta 2 : PSIPQQEHTAVAKHGPTEKTLR gil20553669 C05ADEE16G02. 0774. 0776. 3. dta 0154ADEE16G02. 1176. 1182. 3. dta 3 : QEHDLVFAVR gil21243872

C05ADEE16G02. 2409. 2409. 1. dta C07ADEE16G02. 2419. 2421. 2. dta 0145ADEE17G02. 2755. 2781. 1. dta 2 : RILNRLQPR gil17456789 C07ADEE16G02. 0605. 0605. 3. dta 0154ADEE16G02. 0996. 0998. 3. dta 3 : RIMVITVSLIMLR gi ! 14042829 C07ADEE16G02. 1042. 1044. 3. dta C05ADEE16G02. 1043. 1045. 3. dta 0154ADEE16G02. 1446. 1474. 3. dta 2 : RLGSVQR gil20551188 C07ADEE16G02. 0597. 0599. 2. dta C05ADEE16G02. 0598. 0600. 2. dta 2 : RPAPSGGASGDLRAFGTR gil1082358 C07ADEE16G02. 0580. 0583. 3. dta C05ADEE16G02. 0584. 0586. 3. dta 2 : RQDELIVLNVSGR gi ! 14739334 C07ADEE16G02. 2998. 3006. 2. dta C05ADEE16G02. 3002. 3002. 2. dta 3 : RQQMQDFFLAHK gil10952524 C07ADEE16G02. 0623. 0627. 3. dta C05ADEE16G02. 0633. 0637. 3. dta 0145ADEE17G02. 1032. 1034. 3. dta 2 : RSPTGSTTSRASTVSTK gil7513102 C05ADEE16G02. 1110. 1144. 3. dta 0154ADEE16G02. 1522. 1546. 3. dta 2 : RYNLSLLQTLMFNSARMSFR gi ! 18978275 C07ADEE16G02. 1968. 1972. 3. dta 0154ADEE16G02. 2341. 2351. 3. dta 2 : SAFKAVLHQPLKVIR girl7662659 C05ADEE16G02. 1503. 1507. 3. dta 0145ADEE17G02. 1511. 1513. 3. dta C07ADEE16G02. 1511. 1513. 3. dta 2 : SEAEDASLLSFMQGYMK gil224917 C07ADEE16G02. 2192. 2192. 3. dta 0154ADEE16G02. 2546. 2552. 2. dta 2 : SGSYSYLEERK gil21360806 C07ADEE16G02. 0936. 0938. 2. dta C05ADEE16G02. 0941. 0943. 2. dta 3 : SIVHPSYNSNTLNNDIMLIK gil15988427 C07ADEE16G02. 1517. 1519. 3. dta C07ADEE16G02. 1673. 1673. 3. dta 0145ADEE17G02. 1908. 1910. 2. dta 2 : SNDMNWAHRASR gil106716 C05ADEE16G02. 2136. 2188. 2. dta 0145ADEE17G02. 2567. 2583. 2. dta 4 : SPLGEEMR gil2392352 C05ADEE16G02. 0821. 0823. 2. dta C07ADEE16G02. 0821. 0823. 2. dta C05ADEE16G02. 0832. 0832. 2. dta 0145ADEE17G02. 1227. 1229. 2. dta 0154ADEE16G02. 1228. 1230. 2. dta C05ADEE16G02. 1228. 1230. 2. dta 2 : SQNDFDLVPWLQIATQLISK gil1154664 C05ADEE16G02. 1068. 1070. 3. dta C07ADEE16G02. 1070. 1072. 3. dta 2 : SSSVGCLAEASAR gil10047175 0154ADEE16G02. 1222. 1224. 2. dta 0145ADEE17G02. 1225. 1225. 2. dta C07ADEE16G02. 1225. 1225. 2. dta 3 : TATSEYQTFFNPR gill335344 0145ADEE17G02. 1406. 1408. 2. dta C05ADEE16G02. 1406. 1408. 2. dta C07ADEE16G02. 1415. 1421. 2. dta 0145ADEE17G02. 1812. 1812. 2. dta 2 : TMGYSQEIVEK gil20562022 C05ADEE16G02. 2009. 2009. 1. dta 0145ADEE17G02. 2388. 2390. 1. dta 2 : TSPSNSKNICMPTTDNNNNSSSSTDDTK gil256818 C05ADEE16G02. 0973. 0979. 3. dta 0145ADEE17G02. 1381. 1381. 3. dta 2 : TVFPGAVPVLPASPPPK gill0864047 C07ADEE16G02. 0849. 0855. 3. dta 0145ADEE17G02. 1356. 1358. 2. dta 0154ADEE16G02. 1356. 1358. 2. dta C05ADEE16G02. 1356. 1358. 2. dta 2 : VESLFLDERMSLTQRIGK gil17457181 C05ADEE16G02. 0842. 0842. 3. dta 0154ADEE16G02. 1238. 1240. 3. dta 2 : VGFYESDVMGR gil17455493 C07ADEE16G02. 1290. 1290. 2. dta 0145ADEE17G02. 1683. 1683. 2. dta C07ADEE16G02. 1683. 1683. 2. dta

2 : VIEMVTNLVNINTNK gil20543383 C05ADEE16G02. 1320. 1320. 2. dta C07ADEE16G02. 1331. 1331. 2. dta 2 : VIERYMPRAFGR gilll499504 C05ADEE16G02. 1738. 1738. 2. dta 0154ADEE16G02. 2139. 2145. 2. dta 2 : VLNPPATFLYR gil21232394 C07ADEE16G02. 1265. 1267. 3. dta 0145ADEE17G02. 1657. 1659. 3. dta 3 : VLLPQVGKLFKK gil6322590 C07ADEE16G02. 0747. 0751. 3. dta C05ADEE16G02. 0753. 0753. 3. dta 0154ADEE16G02. 1153. 1155. 3. dta 3 : VTVAGIEQRFCQQCSR gil15227896 C05ADEE16G02. 0960. 0964. 3. dta C07ADEE16G02. 0966. 0968. 3. dta 0145ADEE17G02. 1366. 1368. 3. dta 0154ADEE16G02. 1366. 1368. 3. dta 2 : WIAPAGITHDPR gil21233290 C07ADEE16G02. 2328. 2358. 2. dta 0145ADEE17G02. 2671. 2673. 2. dta 3 : WEQLIAFK gil6759114 C05ADEE16G02. 1871. 1873. 1. dta C07ADEE16G02. 1894. 1896. 1. dta 0145ADEE17G02. 2260. 2264. 1. dta 2 : WQQGHQLAIMKGFQK gil12834350 0154ADEE16G02. 1278. 1280. 3. dta C05ADEE16G02. 1484. 1486. 3. dta 2 : YEDKTCPLKK gil16080632 C05ADEE16G02. 0928. 0928. 1. dta 0145ADEE17G02. 1340. 1340. 1. dta 2 : YLKAIR gil21242998 C05ADEE16G02. 0878. 0880. 1. dta 0145ADEE17G02. 1279. 1279. 1. dta 2 : YSKLKEK gil13431562 C05ADEE16G02. 0462. 0466. 2. dta 0154ADEE16G02. 0560. 0562. 2. dta 2 : YTWHEATLGK gi ! 11065769 C07ADEE16G02. 0637. 0637. 3. dta 0154ADEE16G02. 1010. 1010. 3. dta 3 : Apolipoprotein e [homo sapiens] C05ADEE16G02. 2062.2064. 3. dta 0145ADEE17G02. 2066.2068. 2. dta C05ADEE16G02. 2066.2068. 2. dta C07ADEE16G02. 2082.2082. 2. dta 1: Hypothetical protein xp_106741 [homo sapiens] C05ADEE16G02.0938. 0951.3. dta 1: Similar to glyceraldehyde 3-phosphate dehydrogenase, liver [homo sapiens] 0145ADEE17G02. 2757. 2759. 3. dta Example 3. Proteins and single ions subtracted by either pattern matching or word matching Protein substracted based on both pattern-matching and IDs. gi#11761629#ref#NP_0 : a-alpha fibrinogen [homo sapiens] gi#178345#gb#AAA9879 : alloalbumin venezia [homo sapiens] [mass=69227] gil4502149lreflNP_00 : apolipoprotein a-ii precursor [homo sapiens] gill7873OIgblAABOO48 : apolipoprotein b-100 precursor [homo sapiens] [mass=515558] gi#178855#gb#AAA5176 : apolipoprotein j precursor [homo sapiens] [mass=48803] gi#1314244#gb#AAA997 : complement c4b precursor [homo sapiens] [mass=188405] gi#20545719#ref#XP_0: complement component 3 precursor [homo sapiens] [mass=187148] gil14577919lreflNP_0 : complement component 4a preproprotein; acidic c4 ; rodgers form of c4; complement component 4s [homo sapiens] [mass=192336] gi#1070458#pir##KUHU : ferroxidase (ec 1. 16.3. 1) precursor - human [mass=122652] gi#223918#prf##10043 : fibrinogen alphaa [homo sapiens] [mass=49397] gil20178280lsplP0267 : fibrinogen gamma chain precursor (pro2061)

gil11761631lreflNP_0 : fibrinogen, beta chain preproprotein ; fibrinogen, b beta polypeptide gill6933542lreflNS-0 : fibronectin 1, isoform 1 preproprotein; cold-insoluble globulin gi#1212947#emb#CAA25 : haptoglobin [homo sapiens] [mass=38452] gi#11435220#ref#XP 0 : inter-alpha (globulin) inhibitor, hl polypeptide [homo sapiens] gi#125000#sp#P19823#: inter-alpha-trypsin inhibitor heavy chain h2 precursor (iti heavy chain h2) hyaluronan-associated protein) (shap) gi#229479#prf##74052: lipoprotein gln i [homo sapiens] gi#178775#gb#AAA5174 : proapolipoprotein [homo sapiens] [mass=28962] gil20551100lreflXP-0 : similar to dj34f7. 4 (complement component 4a) [homo sapiens] Protein subtracted based on names.

No Match with the same name, but different IDs Common Single Ions Between Patient and Control Groups AKRELSQGISK: gil20471541 patient: 2 12ADEE15G02. 0958.0960. 2. dta 18ADEE16G02. 0978.0980. 2. dta control: 2 C07ADEE16G02. 0966.0968. 2. dta 0145ADEE17G02. 1366.1368. 2. dta 0154ADEE16G02. 1366.1368. 2. dta APKPKAAK: gil4885377 patient: 3 31ADEE16G02. 0685.0689. 2. dta 20ADEE16G02. 0698.0700. 2. dta 18ADEE16G02. 0705.0707. 2. dta control: 2 C07ADEE16G02. 0700.0702. 2. dta 0145ADEE17G02. 1100.1102. 2. dta EALAKGK: gil4885231 patient: 3

12ADEE15G02. 0655.0655. 2. dta 20ADEE16G02. 0668.0670. 2. dta 18ADEE16G02. 0679.0681. 2. dta control: 2 C05ADEE16G02. 0670.0674. 2. dta 0154ADEE16G02. 1071.1073. 2. dta EHVDVIAK: gil20544347 patient: 2 31ADEE16G02. 1267.1271. 1. dta 18ADEE16G02. 1293. 1293. 1. dta control: 3 C05ADEE16G02.1285. 1287.1. dta C07ADEE16G02. 1286.1288. 1. dta 0154ADEE16G02. 1679.1681. 1. dta FEDGVLDPDYPR: gil139653 patient: 3 20ADEE16G02. 1301.1303. 2. dta 31ADEE16G02. 1306.1312. 2. dta 12ADEE15G02. 1325.1327. 2. dta 18ADEE16G02. 1325.1327. 2. dta control: 2 C05ADEE16G02. 1316.1318. 2. dta 0145ADEE17G02. 1725.1725. 2. dta FEEHKNEKDMAK: gil4894370 patient: 3 12ADEE15G02. 1523.1552. 2. dta 12ADEE15G02. 1556.1558. 2. dta 20ADEE16G02. 1556.1558. 2. dta 18ADEE16G02. 1563.1563. 2. dta control: 2 0145ADEE17G02. 1561.1563. 2. dta 0154ADEE16G02. 1561.1563. 2. dta C05ADEE16G02. 1561.1563. 2. dta C07ADEE16G02. 1571.1575. 2. dta FSEMQNERR: gil21361704 patient: 2 20ADEE16G02. 2009.2015. 2. dta 20ADEE16G02. 2021.2023. 2. dta 31ADEE16G02. 2021. 2023. 2. dta control: 2 C05ADEE16G02. 2017.2019. 2. dta 0145ADEE17G02. 2400.2404. 2. dta HTLNQIDEVK: gil2521981 patient: 3 20ADEE16G02. 0766.0768. 2. dta 18ADEE16G02. 0772.0774. 2. dta 31ADEE16G02. 0773. 0773. 2. dta

control: 2 0154ADEE16G02. 1172. 1174. 2. dta C05ADEE16G02.1172. 1174.2. dta 0145ADEE17G02. 1173.1175. 2. dta LDDIVDSVLATGIQR: gi ! 11359042 patient: 2 12ADEE15G02. 1735.1735. 2. dta 18ADEE16G02. 1735.1735. 2. dta 31ADEE16G02. 1740.1746. 2. dta control: 2 C05ADEE16G02. 1730.1732. 2. dta C07ADEE16G02. 1744.1744. 2. dta PAERGLPAPK: gi ! 1076013 patient: 4 20ADEE16G02. 1865.1869. 2. dta 12ADEE15G02. 1870.1874. 2. dta 31ADEE16G02. 1873.1877. 2. dta 18ADEE16G02. 1873.1879. 2. dta control: 3 C05ADEE16G02. 1867.1869. 2. dta C07ADEE16G02. 1886.1892. 2. dta 0145ADEE17G02. 2256.2258. 2. dta QVVTFVVLLSLCLLK: gi#18572033 patient: 2 18ADEE16G02.1373. 1377.3. dta 12ADEE15G02. 1377.1381. 3. dta control: 3 C05ADEE16G02.1378. 1386.3. dta C07ADEE16G02. 1379.1383. 3. dta 0145ADEE17G02. 1774.1786. 3. dta TYLPAVDEK: gi 1114022 patient: 2 31ADEE16G02. 0957.0959. 2. dta 18ADEE16G02. 0982.0984. 2. dta control: 3 C07ADEE16G02. 0972.0974. 2. dta C05ADEE16G02. 0975.0977. 2. dta 0154ADEE16G02. 1380.1380. 2. dta C05ADEE16G02.1380. 1380.2. dta YVDKAILGDEDDMFR: gi ! 11499013 patient: 2 18ADEE16G02. 1781.1785. 3. dta 12ADEE15G02. 1786.1788. 3. dta control: 3 C05ADEE16G02. 1789.1791. 3. dta C07ADEE16G02. 1796.1798. 3. dta 0145ADEE17G02. 2180.2182. 3. dta

Alpha2-hs glycoprotein [homo sapiens] patient: 4 18ADEE16G02. 1261.1263. 3. dta 31ADEE16G02. 1261.1263. 3. dta 31ADEE16G02. 0764.0766. 2. dta 18ADEE16G02. 1235.1237. 3. dta 31ADEE16G02. 1235.1237. 3. dta 12ADEE15G02. 1252.1254. 3. dta control: 3 C05ADEE16G02. 1255.1265. 3. dta 0145ADEE17G02. 1649.1651. 3. dta C07ADEE16G02. 1261.1269. 3. dta Angiotensinogen (serine (or cysteine) proteinase inhibitor, clade a patient: 3 18ADEE16G02. 1625. 1625. 2. dta 20ADEE16G02. 1604.1606. 2. dta 31ADEE16G02. 2238.2242. 2. dta control: 6 C05ADEE16G02. 2234.2236. 2. dta C07ADEE16G02. 2260.2260. 3. dta C07ADEE16G02. 2828.2830. 3. dta 0145ADEE17G02. 2611.2613. 2. dta 0145ADEE17G02. 2617.2617. 3. dta 0145ADEE17G02. 3185.3187. 3. dta Chain a, crystal structure of benzamidine inhibited bovine pancreatic trypsin at modelled patient: 3 18ADEE16G02. 1523.1527. 2. dta 31ADEE16G02. 1395.1397. 2. dta 12ADEE15G02. 1415.1415. 2. dta control: 2 0154ADEE16G02. 1917.1917. 2. dta C07ADEE16G02. 1523.1532. 2. dta Complement component 5 [homo sapiens] patient: 3 18ADEE16G02. 3297.3299. 3. dta 31ADEE16G02. 3339.3341. 3. dta 12ADEE15G02. 3317.3325. 3. dta control: 2 C05ADEE16G02. 3354.3356. 3. dta C07ADEE16G02. 3354.3358. 3. dta Ig heavy chain-human patient: 1 18ADEE16G02. 0768.0770. 2. dta 31ADEE16G02. 0768.0770. 2. dta control: 3 C05ADEE16G02. 0774.0776. 2. dta

C07ADEE16G02. 0765.0767. 2. dta 0154ADEE16G02. 1176.1182. 2. dta Lipoprotein ciii [homo sapiens] patient: 1 18ADEE16G02. 2158.2166. 2. dta control: 5 C05ADEE16G02. 0953.0955. 2. dta C05ADEE16G02.2170. 2178.2. dta C07ADEE16G02. 0948.0954. 2. dta 0145ADEE17G02. 2551.2555. 2. dta 0145ADEE17G02. 1356.1358. 2. dta 0154ADEE16G02. 1356.1358. 2. dta C05ADEE16G02. 1356.1358. 2. dta Vitronectin precursor (serum spreading factor) (s-protein) (v75) [contains: vitronectin v65 subunit; vitronectin v10 subunit; somatomedin b] patient: 4 18ADEE16G02.1257. 1257.3. dta 18ADEE16G02. 2076.2076. 2. dta 18ADEE16G02. 1233.1233. 3. dta 31ADEE16G02. 1233.1233. 3. dta 12ADEE15G02. 1315.1321. 2. dta control: 3 0154ADEE16G02. 1641.1645. 3. dta 0145ADEE17G02. 1251.1253. 3. dta C05ADEE16G02. 1251.1253. 3. dta C07ADEE16G02. 1257.1257. 3. dta Common Single Ions Between Patient and Common Groups KTYSPAKYGK: gil5174563 patient: 2 20ADEE16G02. 0683.0685. 2. dta 12ADEE15G02. 0693.0695. 2. dta 18ADEE16G02. 0693.0695. 2. dta common: 2 12ADEE15G02. 0659.0661. 2. dta 0154ADEE16G02. 1085.1087. 2. dta MCDNCCKDSAFERTNITEYCR: gil1172898 patient: 2 20ADEE16G02. 1687.1687. 3. dta 18ADEE16G02. 1693. 1693.3. dta common: 3 C07ADEE16G02. 1716.1718. 3. dta 0154ADEE16G02. 2084.2084. 3. dta

0145ADEE17G02. 2090.2096. 3. dta Common Single Ions Between Control and Common Groups FKGYYKIAR: gil17933636 control: 2 0154ADEE16G02. 1272.1274. 3. dta 0145ADEE17G02. 1275.1281. 3. dta common: 2 C07ADEE16G02. 0869.0873. 3. dta C05ADEE16G02. 0872.0874. 3. dta MAEMLVQLVRRIEK : gil13385746 control: 2 C07ADEE16G02. 0686.0688. 3. dta C05ADEE16G02. 0689.0691. 3. dta common: 2 12ADEE15G02. 0659.0661. 3. dta 0154ADEE16G02. 1085.1087. 3. dta Example 4. Unique proteins in patient group Proteins sharing keywords with the subtracted.

(Format: Protein name and IDs: Keywords) gil178853lgblASB5939 apolipoprotein e [homo sapiens] [mass=36207]: apolipoprotein 31ADEE16G02. 2065.2067. 2. dta 12ADEE15G02. 2002.2002. 2. dta 12ADEE15G02. 0677.0679. 2. dta 31ADEE16G02. 0677.0679. 2. dta 20ADEE16G02. 1184.1190. 2. dta 18ADEE16G02. 1201 ; 1215. 2. dta 31ADEE16G02. 2061.2063. 3. dta 18ADEE16G02. 1361.1361. 2. dta 18ADEE16G02. 1028.1028. 2. dta 31ADEE16G02. 1028.1030. 2. dta 31ADEE16G02. 2007.2011. 2. dta 12ADEE15G02. 0781.0781. 2. dta 31ADEE16G02. 0781.0781. 2. dta 12ADEE15G02. 1015.1015. 2. dta 20ADEE16G02. 1015.1017. 2. dta 18ADEE16G02. 1990.1996. 2. dta 20ADEE16G02. 1350.1352. 2. dta 18ADEE16G02. 0719.0725. 2. dta 18ADEE16G02. 0689.0689. 2. dta 31ADEE16G02. 0685.0689. 2. dta

18ADEE16G02. 2048.2056. 2. dta 12ADEE15G02. 0781.0781. 2. dta 31ADEE16G02. 0781.0781. 2. dta 12ADEE15G02. 1011.1013. 2. dta 20ADEE16G02. 1013.1013. 2. dta 18ADEE16G02. 2046.2050. 3. dta 12ADEE15G02. 2000.2000. 2. dta 12ADEE15G02. 0867.0867. 2. dta 18ADEE16G02. 0867.0869. 2. dta 20ADEE16G02. 0867.0869. 2. dta The Rest of the Unique Proteins. gil577055lembICAA249 : gamma-fibrinogen chain fragment [homo sapiens] [mass=7031] 18ADEE16G02. 1453. 1461. 2. dta 31ADEE16G02. 1427.1429. 2. dta 12ADEE15G02. 1439.1455. 2. dta 20ADEE16G02. 1440.1442. 2. dta gill7066105lemblCADl : titin [homo sapiens] [mass=3816218] 12ADEE15G02. 0948.0950. 2. dta 20ADEE16G02. 0941.0943. 2. dta 12ADEE15G02. 0937.0939. 2. dta 18ADEE16G02. 0937.0939. 2. dta 31ADEE16G02. 0937.0939. 2. dta 18ADEE16G02. 1565.1572. 3. dta 31ADEE16G02. 1913.1915. 3. dta 12ADEE15G02. 0532.0534. 3. dta 18ADEE16G02.1755. 1761.3. dta 12ADEE15G02. 1260.1262. 3. dta 31ADEE16G02. 1089.1119. 2. dta 12ADEE15G02. 1556.1558. 2. dta 20ADEE16G02. 1556.1558. 2. dta Summary list, refer above for IDs and DTA files. apolipoprotein e [homo sapiens] [mass=36207] gamma-fibrinogen chain fragment [homo sapiens] [mass=7031] titin [homo sapiens] [mass=3816218] Example 5. Unique single ions in patient group Unique Single Ions in Patient Group, With Multiple Sample Matches For Peptides 2: AADDTWEPFASGK gil2135953 12ADEE15G02. 1383. 1383. 2. dta 18ADEE16G02. 1391. 1395. 2. dta 2 : AAKGAKPEPAPAPPPPGAK gi ! 18598655 31ADEE16G02. 0826. 0828. 3. dta 20ADEE16G02. 0833. 0835. 3. dta 2 : AEDTAVYYCARDIQLDAFDIWGQ gil13171474 18ADEE16G02. 1411. 1411. 3. dta 20ADEE16G02. 1411. 1411. 3. dta 31ADEE16G02. 1411. 1411. 3. dta 18ADEE16G02. 1425. 1427. 3. dta 2 : AETVIIGGGCVGVSLAYHLAKAGMK gil7019365 20ADEE16G02. 1937. 1943. 3. dta 31ADEE16G02. 1949. 1951. 3. dta 2 : APAAAEMLLRSKS gill7451900 31ADEE16G02. 2297. 2347. 2. dta 12ADEE15G02. 2304. 2306. 2. dta 18ADEE16G02. 2304. 2306. 2. dta 2 : APLARLHPPIK gil21244563 18ADEE16G02. 2376. 2380. 1. dta 31ADEE16G02. 2399. 2401. 1. dta 2 : APWIPPNPTSPLASPKCAAWLKVK gil7512882 12ADEE15G02. 0937. 0939. 3. dta 18ADEE16G02. 0937. 0939. 3. dta 31ADEE16G02. 0937. 0939. 3. dta 20ADEE16G02. 0941. 0943. 3. dta 2 : CCGGTVIQTQACTPSR gill8584772 20ADEE16G02. 1060. 1062. 3. dta 18ADEE16G02. 1071. 1079. 3. dta 2 : DINYVNPVIK gil14735486 20ADEE16G02. 1231. 1235. 2. dta 12ADEE15G02. 1240. 1240. 2. dta 2 : DKEFLVFETSDIAISLKWLVEDIK gill2045184 20ADEE16G02. 2495. 2497. 3. dta 31ADEE16G02. 2549. 2551. 3. dta 3 : DKVILLDETLNAIATELKPR gil13508310 31ADEE16G02. 0843. 0853. 3. dta 12ADEE15G02. 0851. 0855. 3. dta 18ADEE16G02. 0871. 0873. 3. dta 20ADEE16G02. 0871. 0873. 3. dta 2 : DSALSTPRAELAQQWFVLALR gil21231993 20ADEE16G02. 1174. 1176. 3. dta 12ADEE15G02. 1188. 1192. 3. dta

2 : DVEGDSVPK gil20482245 31ADEE16G02. 0817. 0822. 2. dta 18ADEE16G02. 0827. 0829. 2. dta 20ADEE16G02. 0827. 0829. 2. dta 2 : DVWGIEGPIDAAFTR girl139653 20ADEE16G02. 2049. 2053. 2. dta 31ADEE16G02. 2083. 2087. 2. dta 2 : DYWSTVK gui) 224917 31ADEE16G02. 1034. 1036. 1. dta 12ADEE15G02. 1054. 1060. 2. dta 2 : EGAGSSALK gil10436629 31ADEE16G02. 0904. 0908. 2. dta 20ADEE16G02. 0915. 0917. 2. dta 2 : EHSGTRLHPCTRCTVK gi|20548673 31ADEE16G02. 1762. 1766. 2. dta 18ADEE16G02. 1773. 1773. 2. dta 2 : ENLSPEDFK gil15668768 12ADEE15G02. 0722. 0722. 2. dta 20ADEE16G02. 0729. 0735. 2. dta 2 : EPAEKPGLGR gil11498871 20ADEE16G02. 0939. 0945. 2. dta 18ADEE16G02. 0962. 0964. 2. dta 2 : EQGISLANVVPHK gil7435945 31ADEE16G02. 0813. 0813. 3. dta 12ADEE15G02. 0819. 0819. 3. dta 20ADEE16G02. 0819. 0819. 3. dta 2 : GPEGIGKPGAAGAPGQPGIPGTK gil18105032 20ADEE16G02. 1440. 1442. 3. dta 18ADEE16G02. 1453. 1461. 3. dta 2 : GQPKDATDWCCQKHDCCYAHLK gil7242177 18ADEE16G02. 2382. 2386. 3. dta 31ADEE16G02. 2393. 2395. 3. dta 2 : GSPAINVAVHVFR gil1336728 20ADEE16G02. 1354. 1356. 2. dta 12ADEE15G02. 1356. 1356. 2. dta 2 : GWVTDGFSSLK gil224917 12ADEE15G02. 1590. 1594. 2. dta 12ADEE15G02. 1592. 1592. 1. dta 2 : HQLWSSPPR gi ! 14783228 18ADEE16G02. 1737. 1745. 2. dta 20ADEE16G02. 1743. 1743. 2. dta 2 : IDDLFDQLKGARVFSK git 6002795 20ADEE16G02. 1821. 1823. 3. dta 18ADEE16G02. 1833. 1835. 3. dta 20ADEE16G02. 1833. 1835. 3. dta 2 : IELEHSIGAIQHSLSR gil16077314 20ADEE16G02. 1436. 1438. 3. dta 18ADEE16G02. 1447. 1447. 3. dta 2 : KAWARK git 9827811 12ADEE15G02. 0929. 0929. 2. dta 20ADEE16G02. 0949. 0949. 2. dta 31ADEE16G02. 0949. 0949. 2. dta 2 : KIILTESYCKSELCILSTQTR gil18595923 12ADEE15G02. 0781. 0781. 3. dta 31ADEE16G02. 0781. 0781. 3. dta 20ADEE16G02. 0792. 0794. 3. dta 2 : KSIKIDDLK gill6804979 18ADEE16G02. 0845. 0845. 2. dta 20ADEE16G02. 0845. 0845. 2. dta 18ADEE16G02. 0853. 0853. 2. dta 2 : LAAQLFSNTTANAIR gil422517 31ADEE16G02. 1163. 1171. 2. dta 12ADEE15G02. 1176. 1210. 2. dta 2 : LAMRGYPMLTTMCPGPQKK gil20546026 12ADEE15G02. 0821. 0825. 3. dta 18ADEE16G02. 0835. 0839. 3. dta 2 : LGALNSSLQLLEDRLHQLSLK gi ! 14043093 12ADEE15G02. 0795. 0795. 3. dta 31ADEE16G02. 0795. 0795. 3. dta 20ADEE16G02. 0798. 0800. 3. dta 2 : LHEMNKHEETVSVAMR gil20468266 12ADEE15G02. 1040. 1040. 3. dta 31ADEE16G02. 1040. 1040. 3. dta 20ADEE16G02. 1049. 1058. 3. dta 2 : LIEPICPQFAEYVWRK gil8569090 20ADEE16G02. 1709. 1709. 2. dta 12ADEE15G02. 1723. 1723. 2. dta 2 : LIQLKPQEEETHDEIFGGLSKVHQK gil20482517 18ADEE16G02. 1931. 1931. 3. dta 12ADEE15G02. 1934. 1934. 3. dta 2 : LLLNKSASAQNELMLLDMLK gill9ll5107

20ADEE16G02. 1013. 1013. 3. dta 12ADEE15G02. 1015. 1015. 3. dta 2 : LMDQNLK gil14010352 12ADEE15G02. 0915. 0915. 1. dta 20ADEE16G02. 0919. 0919. 1. dta 2 : LQKAIEEEEARMR gil11360154 20ADEE16G02. 0927. 0929. 3. dta 18ADEE16G02. 0943. 0945. 3. dta 31ADEE16G02. 0943. 0945. 3. dta 2 : LSDAEPEVR gil20480773 20ADEE16G02. 0776. 0778. 2. dta 18ADEE16G02. 0784. 0786. 2. dta 2 : LSILTEK gil20546459 12ADEE15G02. 0564. 0566. 1. dta 20ADEE16G02. 0634. 0636. 1. dta 2 : LTLIEKPCPR gil18558922 20ADEE16G02. 1663. 1665. 2. dta 18ADEE16G02. 1677. 1681. 2. dta 2 : MTSSFHGIRPPQLEQPEKMPVLK gil12839853 20ADEE16G02. 1273. 1275. 3. dta 12ADEE15G02. 1280. 1282. 3. dta 2 : NAMRVTLDATGNEGSWLFIQPFWK gill7366458 12ADEE15G02. 0805. 0815. 3. dta 18ADEE16G02. 0814. 0820. 3. dta 2 : NGDDSDNGDGADVK gil11061640 20ADEE16G02. 1281. 1281. 3. dta 12ADEE15G02. 1287. 1289. 3. dta 2 : NIAQFGEMIRLKTGR gil346690 18ADEE16G02. 2124. 2124. 2. dta 12ADEE15G02. 2134. 2138. 2. dta 2 : NIHFSWDILAK gi ! 11078753 12ADEE15G02. 2294. 2298. 1. dta 18ADEE16G02. 2318. 2322. 1. dta 2 : NLLENLSGGSTFK gil2129238 31ADEE16G02. 0748. 0748. 2. dta 18ADEE16G02. 0761. 0761. 2. dta 2 : NPAIFGFLLSAK gil6319547 12ADEE15G02. 1025. 1027. 3. dta 12ADEE15G02. 1044. 1046. 3. dta 18ADEE16G02. 1044. 1046. 3. dta 2 : PLTTSPAPAPPPR gil14747828 20ADEE16G02. 1047. 1053. 2. dta 12ADEE15G02. 1052. 1056. 2. dta 2 : PSGNSSSGGKIWQGEPARVR gil5453900 31ADEE16G02. 0748. 0748. 3. dta 18ADEE16G02. 0761. 0761. 3. dta 2 : PSPQRNTTNDIAHIQNEEIMSLQMK gil20554181 20ADEE16G02. 1910. 1925. 3. dta 12ADEE15G02. 1922. 1924. 3. dta 2 : QDFTVKTVSGER gil20470381 12ADEE15G02. 0807. 0809. 3. dta 20ADEE16G02. 0807. 0809. 3. dta 18ADEE16G02. 0812. 0812. 3. dta 2 : QDMIVRTTQEKLK gil20070257 18ADEE16G02. 0845. 0845. 3. dta 20ADEE16G02. 0845. 0845. 3. dta 18ADEE16G02. 0853. 0853. 3. dta 4 : QIFSILAATPGVQVEK gi) 11061648 31ADEE16G02. 1087. 1097. 3. dta 12ADEE15G02. 1108. 1110. 3. dta 20ADEE16G02. 1112. 1116. 3. dta 18ADEE16G02. 1126. 1136. 3. dta 2 : QPTQEEILFQVAQAGEVDK gil1708635 20ADEE16G02. 1156. 1160. 3. dta 12ADEE15G02. 1167. 1169. 3. dta 2 : QPVPAGWPGWYER gil21233559 18ADEE16G02. 1833. 1835. 3. dta 20ADEE16G02. 1833. 1835. 3. dta 12ADEE15G02. 1840. 1840. 3. dta 2 : QTDEQLHRMGAPR gil21241051 20ADEE16G02. 1739. 1741. 2. dta 31ADEE16G02. 1853. 1855. 2. dta 2 : QYEQNIMDHKLNLDLLTQSTSSSR gil20536830 18ADEE16G02. 1656. 1662. 3. dta 12ADEE15G02. 1661. 1661. 3. dta 2 : RDRAPFVFTSDMAYVINGGDK gil13632400 31ADEE16G02. 0621. 0623. 3. dta 18ADEE16G02. 0637. 0639. 3. dta 2 : RIADLRSDLGPEIR gil21230680 12ADEE15G02. 1731. 1739. 1. dta 18ADEE16G02. 1731. 1757. 1. dta

4 : SKEQLTPLIK girl4502149 31ADEE16G02. 0912. 0914. 2. dta 20ADEE16G02. 0933. 0935. 2. dta 20ADEE16G02. 0949. 0949. 3. dta 31ADEE16G02. 0949. 0949. 3. dta 18ADEE16G02. 0949. 0952. 3. dta 2 : SLPWSAARQLR gil21231002 12ADEE15G02. 0439. 0441. 3. dta 31ADEE16G02. 0499. 0501. 3. dta 2 : SLSLAQNLLER gil18560704 20ADEE16G02. 1074. 1096. 2. dta 18ADEE16G02. 1091. 1120. 2. dta 3 : SPELQAEAK gil4502149 12ADEE15G02. 0612. 0614. 2. dta 20ADEE16G02. 0612. 0614. 2. dta 12ADEE15G02. 0616. 0618. 1. dta 31ADEE16G02. 0635. 0637. 1. dta 4 : SSGTSYPDVLK gi ! 15988427 31ADEE16G02. 0975. 0977. 2. dta 20ADEE16G02. 0987. 0989. 2. dta 12ADEE15G02. 0991. 0993. 2. dta 18ADEE16G02. 1004. 1010. 2. dta 2 : SSQSVLYSSNSK girl1730075 18ADEE16G02. 1992. 1994. 2. dta 31ADEE16G02. 2013. 2015. 2. dta 3 : SSSRPKVSATAAAAAGK gil8250399 20ADEE16G02. 1019. 1021. 2. dta 12ADEE15G02. 1038. 1038. 1. dta 18ADEE16G02. 1040. 1042. 2. dta 2 : TIENSQCTKVEEDFNLATKIISK gi) 13469731 31ADEE16G02. 2254. 2256. 3. dta 20ADEE16G02. 2262. 2266. 3. dta 2 : TQLQSFSQYIENRPEMK gill7441098 31ADEE16G02. 1445. 1457. 3. dta 12ADEE15G02. 1451. 1453. 3. dta 2 : VAVARAQGLGGQLR gil21231008 18ADEE16G02. 2338. 2342. 2. dta 31ADEE16G02. 2371. 2371. 2. dta 3 : VEGNEVIIENFIGEK gi) 11499493 18ADEE16G02. 2280. 2282. 2. dta 31ADEE16G02. 2285. 2287. 2. dta 31ADEE16G02. 2291. 2311. 1. dta

4: VKSPELQAEAK gil4502149 12ADEE15G02. 0645.0647. 2. dta 12ADEE15G02. 0651. 0653. 2. dta 31ADEE16G02. 0651.0653. 2. dta 20ADEE16G02. 0658.0660. 2. dta 18ADEE16G02. 0667.0669. 2. dta 31ADEE16G02. 0667.0669. 2. dta 3: VPGPAFGHQIAYCNLLPR gi) 20538746 31ADEE16G02. 0881.0885. 3. dta 20ADEE16G02. 0891.0895. 3. dta 18ADEE16G02. 0904.0906. 3. dta 2: VYVSLGALKMHIRTHTLPCK gil399449 31ADEE16G02. 2469.2505. 3. dta 18ADEE16G02. 2482.2486. 3. dta 2: YIHTGEK gill3374557 20ADEE16G02. 0893.0893. 2. dta 12ADEE15G02. 0893.0895. 2. dta 2: YWITADK gil19115051 12ADEE15G02. 1042.1050. 1. dta 18ADEE16G02. 1057.1059. 1. dta 6: Apolipoprotein a-ii precursor [homo sapiens] 12ADEE15G02. 0925.0927. 2. dta 20ADEE16G02. 2683.2685. 2. dta 31ADEE16G02. 0659.0663. 3. dta 31ADEE16G02. 2745.2759. 2. dta 31ADEE16G02. 2753.2765. 3. dta 31ADEE16G02. 2904.2918. 3. dta 1: C9 complement protein [homo sapiens] 18ADEE16G02. 1799.1799. 2. dta 1: Chain c, crystal structure of the human alpha-thrombin-haemadin complex: an exosite ii-binding inhibitor 20ADEE16G02. 1436.1438. 2. dta 1: Gvpl gene in phhl homolog [rhizobium rhizogenes] 18ADEE16G02. 1749.1751. 3. dta 1: Prothrombin [homo sapiens] 20ADEE16G02. 1401.1405. 2. dta 31ADEE16G02. 1401.1405. 2. dta The examples illustrate the summarization of Groupl unique_with_name ; Group2 unique_with_name ; Groupl-unique

without-name and Group2uniquewithoutname ; wherein Groupuniquewithoutname list is used for optional databases searches, and Group_unique_with_name list is used directly for further analysis such as data mining.

It is to be understood that while we have illustrated and described certain forms of our invention, it is not to be limited to the specific forms or arrangement of the steps herein described and shown. It will be apparent to those skilled in the art that various changes may be made without departing from the scope of the invention and the invention is not to be considered limited to what is shown in the drawings and described in the specification.

Although the instant invention has been exemplified in the context of an ion-trap device, it is to be understood that the sample mass may be analyzed by any combination of ionization and mass spectrometer. The ionization method may include, but is not limited to such methods as electron ionization, chemical ionization, fast atom bombardment, desorption chemical ionization, plasmadeorption, thermospray, atmospheric pressure chemical ionization, MALDI or electrospray ionization (ESI). Principally the ionization method will be MALDI or ESI.

Prior art mass spectrometer formats are known to be useful either singly or in various combinations for use

in analyzing translation products. These formats may include, but are not limited to, ionization (I) techniques, including but not limited to matrix assisted laser desorption (MALDI), continuous or pulsed electrospray (ESI) and related methods (e. g. , IONSPRAY or THERMOSPRAY), or massive cluster impact (MCI); these ion sources can be matched with detection formats including linear or non-linear reflection time-of-flight (TOF), single or multiple quadropole, single or multiple magnetic sector, Fourier Transform ion cyclotron resonance (FTICR), ion trap, and combinations thereof (e. g. , ion-trap/time-of-flight). For ionization, numerous matrix/wavelength combinations (MALDI) or solvent combinations (ESI) can be employed. Subattomole levels of protein have been detected, for example, using ESI (Valaskovic, G. A. et al. , (1996) Science 273: 1199-1202) or MALDI (Li, L. et al. , (1996) J. Am. Chem. Soc.

118: 1662-1663) mass spectrometry. ES mass spectrometry has been introduced by Fenn et al. (J. Phys. Chem. 88, 4451-59 (1984); PCT Application No. WO 90/14148) and current applications are summarized in recent review articles (R. D. Smith et al., Anal. Chem. 62,882-89 (1990) and B. Ardrey, Electrospray Mass Spectrometry, Spectroscopy Europe, 4,10-18 (1992) ). MALDI-TOF mass spectrometry has been introduced by Hillenkamp et al.

("Matrix Assisted UV-Laser Desorption/Ionization: A New Approach to Mass Spectrometry of Large Biomolecules,"

Biological Mass Spectrometry (Burlingame and McCloskey, editors), Elsevier Science Publishers, Amsterdam, pp.

49-60,1990). With ESI, the determination of molecular weights in femtomole amounts of sample is very accurate due to the presence of multiple ion peaks which all could be used for the mass calculation.

With regard to electrospray, an electrospray is produced by applying a strong electric field under atmospheric pressure to a liquid passing through a capillary tube with a weak flux. The electric field is obtained by applying a potential difference of 3-6 kV between the capillary and the counter electrode separate by 0.3 to 2 cm producing electric fields of the order of 10 E6 V per cm. This field induces a charge at the liquid surface located at the end of capillary, which will break to form highly charged droplets. A gas injected co-axially at a low flow rate allows the dispersion of the spray to be limited in space. These droplets then pass either through a curtain of heated inert gas, most often nitrogen, or through a heated capillary to remove the last solvent molecules. "See for example"Mass spectrometry, principle and application" 2nd edition. 2001. Edmond de Hoffmann and Vincent Stroobant. John Wiley & Sons, New York. Page 35.

With regard to the mass spectrometer, per se, there are several types of tandem mass spectrometers that could be used to generate the patterns of MS/MS spectra that

are the substrate for the program. These mass spectrometers generate both parent ions in the +1 (MALDI and ESI) and the +2, +3, +4 etc charge state (ESI). The program takes the charge state of the parent into consideration as part of the data associated with the parent ion. The types of mass analyzer mass analyzers include the quadropole, octopole, ion trap or QUISTOR, time of flight (TOF) Time of Flight with reflectron, the Fourier transformed ion cyclotron resonance (FTICR also called FTMS), magnetic and electromagnetic sector. The tandem mass spectrometer mass consist of the homogenous or heterogenous combination of two or more of any of these devices in any order (Hybrid instrument). The fragmentation method may include post source decay of the parent ion or its fragment, or collision-activated or collision-induced decomposition of the parent ions, or fragment ions, or metastable ions with a relatively immobile target such as gas molecules or other parent or fragment ions, or photons or electrons or solid objects.

The combinations may preferentially include the quadropole or octopole ion trap, the Quadropole-Quadropole (DC and rf or rf only) -TOF, the ion trap-FTMS, the TOF-TOF, the ion trap-TOF, or the TOF-PSD-TOF. The signal resulting from the instrument may be mathematically transformed or filtered. The MASS analyzer may be directly or indirectly coupled to a number of devices, which are illustrated by, but not limited to, liquid chromatography or capillary electrophoresis, or free flow electrophoresis, or gel electrophoresis, or multidimensional chromatography, or multidimensional electrophoresis.