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Proteomics: the first decade and beyond

Nature Genetics volume 33, pages 311–323 (2003)Cite this article

Abstract

Proteomics is the systematic study of the many and diverse properties of proteins in a parallel manner with the aim of providing detailed descriptions of the structure, function and control of biological systems in health and disease. Advances in methods and technologies have catalyzed an expansion of the scope of biological studies from the reductionist biochemical analysis of single proteins to proteome-wide measurements. Proteomics and other complementary analysis methods are essential components of the emerging 'systems biology' approach that seeks to comprehensively describe biological systems through integration of diverse types of data and, in the future, to ultimately allow computational simulations of complex biological systems.

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Figure 1: Representation of a eukaryotic cell.

Katie Ris

Figure 2: The current status of proteomic technologies.

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Figure 3: Quantitative protein analysis from the cell to the identified protein.

Katie Ris

Figure 4: Time line indicating the convergence of different technologies and resources into a proteomic process.

Katie Ris

Figure 5: Quantitative proteomics using ICAT reagents.

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Figure 6: Quantitative proteomics and informatics.

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References

  1. Aebersold, R., Hood, L.E. & Watts, J.D. Equipping scientists for the new biology. Nat. Biotechnol. 18, 359 (2000).

    Article  CAS  PubMed  Google Scholar 

  2. Thornton, J. Structural genomics takes off. Trends Biochem. Sci. 26, 88–99 (2001).

    Article  CAS  PubMed  Google Scholar 

  3. Aebersold, R. & Patterson, S.D. Current problems and technical solutions in protein biochemistry. In PROTEINS: Analysis & Design (ed. Angeletti, R.H.) 3–120 (Academic, San Diego, 1998).

    Chapter  Google Scholar 

  4. Adams, M.D. et al. Initial assessment of human gene diversity and expression patterns based upon 83 million nucleotides of cDNA sequence. Nature 377, 3–174 (1995).

    CAS  PubMed  Google Scholar 

  5. Schena, M., Shalon, D., Davis, R.W. & Brown, P.O. Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science 270, 467–470 (1995).

    Article  CAS  PubMed  Google Scholar 

  6. Velculescu, V.E., Zhang, L., Vogelstein, B. & Kinzler, K.W. Serial analysis of gene expression. Science 270, 484–487 (1995).

    Article  CAS  PubMed  Google Scholar 

  7. Anderson, N.L., Hofmann, J.P., Gemmell, A. & Taylor, J. Global approaches to quantitative analysis of gene-expression patterns observed by use of two-dimensional gel electrophoresis. Clin. Chem. 30, 2031–2036 (1984).

    CAS  PubMed  Google Scholar 

  8. Tarroux, P., Vincens, P. & Rabilloud, T. HERMeS: A second generation approach to the automatic analysis of two-dimensional electrophoresis gels. Part V: Data analysis. Electrophoresis 8, 187–199 (1987).

    Article  CAS  Google Scholar 

  9. Aebersold, R.H., Leavitt, J., Saavedra, R.A., Hood, L.E. & Kent, S.B. Internal amino acid sequence analysis of proteins separated by one- or two-dimensional gel electrophoresis after in situ protease digestion on nitrocellulose. Proc. Natl. Acad. Sci. 84, 6970–6974 (1987).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Vandekerckhove, J., Bauw, G., Puype, M., Van Damme, J. & Van Montagu, M. Protein-blotting on polybrene-coated glass-fiber sheets. Eur. J. Biochem. 152, 9–19 (1985).

    Article  CAS  PubMed  Google Scholar 

  11. Tempst, P., Link, A.J., Riviere, L.R., Fleming, M. & Elicone, C. Internal sequence analysis of proteins separated on polyacrylamide gels at the submicrogram level: improved methods, applications and gene cloning strategies. Electrophoresis 11, 537–553 (1990).

    Article  CAS  PubMed  Google Scholar 

  12. Adams, M.D. et al. Complementary DNA sequencing: expressed sequence tags and human genome project. Science 252, 1651–1656 (1991).

    Article  CAS  PubMed  Google Scholar 

  13. Adams, M.D., Kerlavage, A.R., Fields, C. & Venter, J.C. 3,400 new expressed sequence tags identify diversity of transcripts in human brain. Nat. Genet. 4, 256–267 (1993).

    Article  CAS  PubMed  Google Scholar 

  14. Zhang, L. et al. Gene expression profiles in normal and cancer cells. Science 276, 1268–1272 (1997).

    Article  CAS  PubMed  Google Scholar 

  15. Bonaldo, M.F., Lennon, G. & Soares, M.B. Normalization and subtraction: two approaches to facilitate gene discovery. Genome Res. 6, 791–806 (1996).

    Article  CAS  PubMed  Google Scholar 

  16. Goffeau, A. et al. Life with 6000 genes. Science 274, 563–567 (1996).

    Article  Google Scholar 

  17. Venter, J.C. et al. The sequence of the human genome. Science 291, 1304–1351 (2001).

    Article  CAS  PubMed  Google Scholar 

  18. Lander, E.S. et al. Initial sequencing and analysis of the human genome. Nature 409, 860–921 (2001).

    Article  CAS  PubMed  Google Scholar 

  19. Fenn, J.B., Mann, M., Meng, C.K., Wong, S.F. & Whitehouse, C.M. Electrospray ionization for mass spectrometry of large biomolecules. Science 246, 64–71 (1989).

    Article  CAS  PubMed  Google Scholar 

  20. Karas, M. & Hillenkamp, F. Laser desorption ionization of proteins with molecular masses exceeding 10000 daltons. Anal. Chem. 60, 2299–2301 (1988).

    Article  CAS  PubMed  Google Scholar 

  21. Tanaka, K., Ido, Y., Akita, S., Yoshida, Y. & Yoshida, T. Detection of high mass molecules by laser desorption time-of-flight mass spectrometry. In Proc. 2nd Japan-China Joint Symp. Mass Spectrom. (eds. Matsuda, H. & Xiao-tian, L.) 185–188 (Osaka, Japan, 1987).

    Google Scholar 

  22. Tanaka, K. et al. Protein and polymer analyses up to m/z 100,000 by laser ionization TOF-MS. Rapid Commun. Mass Spectrom. 2, 151–153 (1988).

    Article  CAS  Google Scholar 

  23. Henzel, W.J. et al. Identifying proteins from two-dimensional gels by molecular mass searching of peptide fragments in protein sequence databases. Proc. Natl. Acad. Sci. USA 90, 5011–5015 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Mann, M., Hojrup, P. & Roepstorff, P. Use of mass spectrometric molecular weight information to identify proteins in sequence databases. Biol. Mass Spectrom. 22, 338–345 (1993).

    Article  CAS  PubMed  Google Scholar 

  25. Pappin, D.J.C., Hojrup, P. & Bleasby, A.J. Rapid identification of proteins by peptide-mass fingerprinting. Curr. Biol. 3, 327–332 (1993).

    Article  CAS  PubMed  Google Scholar 

  26. James, P., Quadroni, M., Carafoli, E. & Gonnet, G. Protein identification by mass profile fingerprinting. Biochem. Biophys. Res. Commun. 195, 58–64 (1993).

    Article  CAS  PubMed  Google Scholar 

  27. Yates, J.R., III, Speicher, S., Griffin, P.R. & Hunkapiller, T. Peptide mass maps: a highly informative approach to protein identification. Anal. Biochem. 214, 397–408 (1993).

    Article  CAS  PubMed  Google Scholar 

  28. Patterson, S.D. & Aebersold, R. Mass spectrometric approaches for the identification of gel-separated proteins. Electrophoresis 16, 1791–1814 (1995).

    Article  CAS  PubMed  Google Scholar 

  29. Eng, J.K., McCormack, A.L. & Yates, J.R., III . An approach to correlate tandem mass spectral data pf peptides with amino acid sequences in a protein database. J. Am. Soc. Mass Spectrom. 5, 976–989 (1994).

    Article  CAS  PubMed  Google Scholar 

  30. Mann, M. Sequence database searching by mass spectrometric data. In Microcharacterization of Proteins (eds. Kellner, R., Lottspeich, F. & Meyer, H.E.) 223–245 (VCH, Weinheim, 1994).

    Chapter  Google Scholar 

  31. Gras, R. & Muller, M. Computational aspects of protein identification by mass spectrometry. Curr. Opin. Mol. Ther. 3, 526–532 (2001).

    CAS  PubMed  Google Scholar 

  32. Wilm, M.S. & Mann, M. Electrospray and Taylor-Cone theory, Dole's beam of macromolecules at last? Int. J. Mass Spectrom. Ion Proc. 136, 167–180 (1994).

    Article  CAS  Google Scholar 

  33. Wilm, M. et al. Femtomole sequencing of proteins from polyacrylamide gels by nano-electrospray mass-spectrometry. Nature 379, 466–469 (1996).

    Article  CAS  PubMed  Google Scholar 

  34. Scheele, G.A. Two-dimensional gel analysis of soluble proteins. Characterization of guinea pig exocrine pancreatic proteins. J. Biol. Chem. 250, 5375–5385 (1975).

    CAS  PubMed  Google Scholar 

  35. Klose, J. Protein mapping by combined isoelectric focusing and electrophoresis of mouse tissues: a novel approach to testing for induced point mutations in mammals. Humangenetik 26, 231–243 (1975).

    CAS  PubMed  Google Scholar 

  36. O'Farrell, P.H. High resolution two-dimensional gel electrophoresis of proteins. J. Biol. Chem. 250, 4007–4021 (1975).

    CAS  PubMed  Google Scholar 

  37. Anderson, N.G. & Anderson, L. The human protein index. Clin Chem. 28, 739–748 (1982).

    CAS  PubMed  Google Scholar 

  38. Garrels, J.I. The QUEST system for quantitative analysis of two-dimensional gels. J. Biol. Chem. 264, 5269–5282 (1989).

    CAS  PubMed  Google Scholar 

  39. Garrels, J.I. & Franza, B.R. Jr. Transformation-sensitive and growth-related changes of protein synthesis in REF52 cells. A two-dimensional gel analysis of SV40-, adenovirus-, and Kirsten murine sarcoma virus–transformed rat cells using the REF52 protein database. J. Biol. Chem. 264, 5299–5312 (1989).

    CAS  PubMed  Google Scholar 

  40. Garrels, J.I. & Franza, B.R., Jr. The REF52 protein database. Methods of database construction and analysis using the QUEST system and characterizations of protein patterns from proliferating and quiescent REF52 cells. J. Biol. Chem. 264, 5283–5298 (1989).

    CAS  PubMed  Google Scholar 

  41. Anderson, N.L., Matheson, A.D. & Steiner, S. Proteomics: applications in basic and applied biology. Curr. Opin. Biotechnol. 11, 408–412 (2000).

    Article  CAS  PubMed  Google Scholar 

  42. Wilkins, M.R. et al. Progress with proteome projects: why all proteins expressed by a genome should be identified and how to do it. Biotech. Gen. Eng. Rev. 13, 19–50 (1995).

    Article  Google Scholar 

  43. Gygi, S.P., Rochon, Y., Franza, B.R. & Aebersold, R. Correlation between protein and mRNA abundance in yeast. Mol. Cell. Biol. 19, 1720–1730 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Lai, R. et al. Prognostic value of plasma interleukin-6 levels in patients with chronic lymphocytic leukemia. Cancer 95, 1071–1075 (2002).

    Article  CAS  PubMed  Google Scholar 

  45. Ritchie, R.F., Palomaki, G.E., Neveux, L.M. & Navolotskaia, O. Reference distributions for the negative acute-phase proteins, albumin, transferrin, and transthyretin: a comparison of a large cohort to the world's literature. J. Clin. Lab. Anal. 13, 280–286 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Gygi, S.P., Corthals, G.L., Zhang, Y., Rochon, Y. & Aebersold, R. Evaluation of two-dimensional gel electrophoresis-based proteome analysis technology. Proc. Natl. Acad. Sci. USA 97, 9390–9395 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Corthals, G.L., Wasinger, V.C., Hochstrasser, D.F. & Sanchez, J.C. The dynamic range of protein expression: a challenge for proteomic research. Electrophoresis 21, 1104–1115 (2000).

    Article  CAS  PubMed  Google Scholar 

  48. Gauss, C., Kalkum, M., Lowe, M., Lehrach, H. & Klose, J. Analysis of the mouse proteome. I. Brain proteins: separation by two-dimensional electrophoresis and identification by mass spectrometry and genetic variation. Electrophoresis 20, 575–600 (1999).

    Article  CAS  PubMed  Google Scholar 

  49. Rabilloud, T. Two-dimensional gel electrophoresis in proteomics: old, old fashioned, but it still climbs up the mountains. Proteomics 2, 3–10 (2002).

    Article  CAS  PubMed  Google Scholar 

  50. Herbert, B. Advances in protein solubilisation for two-dimensional electrophoresis. Electrophoresis 20, 660–663 (1999).

    Article  CAS  PubMed  Google Scholar 

  51. Gorg, A. et al. The current state of two-dimensional electrophoresis with immobilized pH gradients. Electrophoresis 21, 1037–1053 (2000).

    Article  CAS  PubMed  Google Scholar 

  52. Unlu, M., Morgan, M.E. & Minden, J.S. Difference gel electrophoresis: a single gel method for detecting changes in protein extracts. Electrophoresis 18, 2071–2077 (1997).

    Article  CAS  PubMed  Google Scholar 

  53. Rabilloud, T., Strub, J.M., Luche, S., van Dorsselaer, A. & Lunardi, J. A comparison between Sypro Ruby and ruthenium II tris (bathophenanthroline disulfonate) as fluorescent stains for protein detection in gels. Proteomics 1, 699–704 (2001).

    Article  CAS  PubMed  Google Scholar 

  54. Appella, E., Padlan, E.A. & Hunt, D.F. Analysis of the structure of naturally processed peptides bound by class I and class II major histocompatibility complex molecules. EXS 73, 105–119 (1995).

    CAS  PubMed  Google Scholar 

  55. Hunt, D.F. et al. Characterization of peptides bound to the class I MHC molecule HLA-A2.1 by mass spectrometry. Science 255, 1261–1263 (1992).

    Article  CAS  PubMed  Google Scholar 

  56. Henderson, R.A. et al. HLA-A2.1-associated peptides from a mutant cell line: a second pathway of antigen presentation. Science 255, 1264–1266 (1992).

    Article  CAS  PubMed  Google Scholar 

  57. Hunt, D.F. et al. Peptides presented to the immune system by the murine class II major histocompatibility complex molecule I-Ad. Science 256, 1817–1820 (1992).

    Article  CAS  PubMed  Google Scholar 

  58. Yates, J.R., III, McCormack, A.L., Schieltz, D., Carmack, E. & Link, A. Direct analysis of protein mixtures by tandem mass spectrometry. J. Prot. Chem. 16, 495–497 (1997).

    Article  CAS  Google Scholar 

  59. Spahr, C.S. et al. Simplification of complex peptide mixtures for proteomic analysis: reversible biotinylation of cysteinyl peptides. Electrophoresis 21, 1635–1650 (2000).

    Article  CAS  PubMed  Google Scholar 

  60. Wolters, D.A., Washburn, M.P. & Yates, J.R. III . An automated multidimensional protein identification technology for shotgun proteomics. Anal. Chem. 73, 5683–5690 (2001).

    Article  CAS  PubMed  Google Scholar 

  61. Link, A.J., Carmack, E. & Yates, J.R. III . A strategy for the identification of proteins localized to subcellular spaces: Application to E-coli periplasmic proteins. Int. J. Mass Spectrom. Ion Proc. 160, 303–316 (1997).

    Article  CAS  Google Scholar 

  62. Link, A.J. et al. Direct analysis of protein complexes using mass spectrometry. Nat. Biotechnol. 17, 676–682 (1999).

    Article  CAS  PubMed  Google Scholar 

  63. Mintz, P.J., Patterson, S.D., Neuwald, A.F., Spahr, C.S. & Spector, D.L. Purification and biochemical characterization of interchromatin granule clusters. EMBO J. 18, 4308–4320 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Patterson, S.D. et al. Mass spectrometric identification of proteins released from mitochondria undergoing permeability transition. Cell Death Diff. 7, 137–144 (2000).

    Article  CAS  Google Scholar 

  65. Spahr, C.S. et al. Towards defining the urinary proteome using liquid chromatography-tandem mass spectrometry I. Profiling an unfractionated tryptic digest. Proteomics 1, 93–107 (2001).

    Article  CAS  PubMed  Google Scholar 

  66. Sanders, S.L., Jennings, J., Canutescu, A., Link, A.J. & Weil, P.A. Proteomics of the eukaryotic transcription machinery: identification of proteins associated with components of yeast TFIID by multidimensional mass spectrometry. Mol. Cell. Biol. 22, 4723–4738 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Verma, R. et al. Proteasomal proteomics: identification of nucleotide-sensitive proteasome-interacting proteins by mass spectrometric analysis of affinity-purified proteasomes. Mol. Biol. Cell 11, 3425–3439 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Han, D.K., Eng, J., Zhou, H. & Aebersold, R. Quantitative profiling of differentiation-induced microsomal proteins using isotope-coded affinity tags and mass spectrometry. Nat. Biotechnol. 19, 946–951 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Simpson, R.J. et al. Proteomic analysis of the human colon carcinoma cell line (LIM 1215): Development of a membrane protein database. Electrophoresis 21, 1707–1732 (2000).

    Article  CAS  PubMed  Google Scholar 

  70. Rout, M.P. et al. The yeast nuclear pore complex: composition, architecture, and transport mechanism. J. Cell Biol. 148, 635–651 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Washburn, M.P., Wolters, D. & Yates, J.R.r Large-scale analysis of the yeast proteome by multidimensional protein identification technology. Nat. Biotechnol. 19, 242–247 (2001).

    Article  CAS  PubMed  Google Scholar 

  72. Patterson, S.D. Using MS fragment-ion data to identify proteins from large sequence databases. In Proteomics, Integrating Protein-based Tools and Applications for Drug Discovery (ed. Savage, L.M.) 127–135 (International Business Communications, Southborough, 1998).

    Google Scholar 

  73. Nuwaysir, L.M. & Stults, J.T. Electrospray ionization mass spectrometry of phosphopeptides isolated by on-line immobilized metal-ion affinity chromatography. J. Am. Soc. Mass Spectrom. 4, 662–669 (1993).

    Article  CAS  PubMed  Google Scholar 

  74. Ficarro, S.B. et al. Phosphoproteome analysis by mass spectrometry and its application to Saccharomyces cerevisiae. Nat. Biotechnol. 20, 301–305 (2002).

    Article  CAS  PubMed  Google Scholar 

  75. Hayes, B.K., Greis, K.D. & Hart, G.W. Specific isolation of O-Linked N-acetylglucosamine glycopeptides from complex mixtures. Anal. Biochem. 228, 115–122 (1995).

    Article  CAS  PubMed  Google Scholar 

  76. Greis, K.D. et al. Selective detection and site-analysis of O-GlcNAc-modified glycopeptides by β-elimination and tandem electrospray mass spectrometry. Anal. Biochem. 234, 38–49 (1996).

    Article  CAS  PubMed  Google Scholar 

  77. Davis, M.T. et al. Automated LC-LC-MS-MS platform using binary ion-exchange and gradient reversed-phase chromatography for improved proteomic analyses. J. Chromatogr. B 752, 281–291 (2001).

    Article  CAS  Google Scholar 

  78. Gygi, S.P., Rist, B., Griffin, T.J., Eng, J. & Aebersold, R. Proteome analysis of low-abundance proteins using multidimensional chromatography and isotope-coded affinity tags. J. Proteome Res. 1, 47–54 (2002).

    Article  CAS  PubMed  Google Scholar 

  79. Smith, R.D. et al. An accurate mass tag strategy for quantitative and high-throughput proteome measurements. Proteomics 2, 513–523 (2002).

    Article  CAS  PubMed  Google Scholar 

  80. De Leenheer, A.P. & Thienpont, L.M. Application of isotope dilution-mass spectrometry in clinical chemistry, pharmacokinetics, and toxicology. Mass Spectrom. Rev. 11, 249–307 (1992).

    Article  CAS  Google Scholar 

  81. Gygi, S.P. et al. Quantitative analysis of complex protein mixtures using isotope-coded affinity tags. Nat. Biotechnol. 17, 994–999 (1999).

    Article  CAS  PubMed  Google Scholar 

  82. Munchbach, M., Quadroni, M., Miotto, G. & James, P. Quantitation and facilitated de novo sequencing of proteins by isotopic N-terminal labeling of peptides with a fragmentation-directing moiety. Anal. Chem. 72, 4047–4057 (2000).

    Article  CAS  PubMed  Google Scholar 

  83. Cagney, G. & Emili, A. De novo peptide sequencing and quantitative profiling of complex protein mixtures using mass-coded abundance tagging. Nat. Biotechnol. 20, 163–170 (2002).

    Article  CAS  PubMed  Google Scholar 

  84. Zhou, H., Ranish, J.A., Watts, J.D. & Aebersold, R. Quantitative proteome analysis by solid-phase isotope tagging and mass spectrometry. Nat. Biotechnol. 20, 512–515 (2002).

    Article  CAS  PubMed  Google Scholar 

  85. Mirgorodskaya, O.A. et al. Quantitation of peptides and proteins by matrix-assisted laser desorption/ionization mass spectrometry using 18O-labeled internal standards. Rapid Commun. Mass Spectrom. 14, 1226–1232 (2000).

    Article  CAS  PubMed  Google Scholar 

  86. Yao, X., Freas, A., Ramirez, J., Demirev, P.A. & Fenselau, C. Proteolytic 18O labeling for comparative proteomics: model studies with two serotypes of adenovirus. Anal. Chem. 73, 2836–2842 (2001).

    Article  CAS  PubMed  Google Scholar 

  87. Uttenweiler-Joseph, S., Neubauer, G., Christoforidis, S., Zerial, M. & Wilm, M. Automated de novo sequencing of proteins using the differential scanning technique. Proteomics 1, 668–682 (2001).

    Article  CAS  PubMed  Google Scholar 

  88. Oda, Y., Huang, K., Cross, F.R., Cowburn, D. & Chait, B.T. Accurate quantitation of protein expression and site-specific phosphorylation. Proc. Natl. Acad. Sci. USA 96, 6591–6596 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Conrads, T.P. et al. Quantitative analysis of bacterial and mammalian proteomes using a combination of cysteine affinity tags and 15N-metabolic labeling. Anal. Chem. 73, 2132–2139 (2001).

    Article  CAS  PubMed  Google Scholar 

  90. Smith, R.D. et al. Rapid quantitative measurements of proteomes by Fourier transform ion cyclotron resonance mass spectrometry. Electrophoresis 22, 1652–1668 (2001).

    Article  CAS  PubMed  Google Scholar 

  91. Washburn, M.P., Ulaszek, R., Deciu, C., Schieltz, D.M. & Yates, J.R. III . Analysis of quantitative proteomic data generated via multidimensional protein identification technology. Anal. Chem. 74, 1650–1657 (2002).

    Article  CAS  PubMed  Google Scholar 

  92. Siebert, R., Rosenwald, A., Staudt, L.M. & Morris, S.W. Molecular features of B-cell lymphoma. Curr. Opin. Oncol. 13, 316–324 (2001).

    Article  CAS  PubMed  Google Scholar 

  93. Bangur, C.S. et al. Identification of genes over-expressed in small cell lung carcinoma using suppression subtractive hybridization and cDNA microarray expression analysis. Oncogene 21, 3814–3825 (2002).

    Article  CAS  PubMed  Google Scholar 

  94. van't Veer, L.J. et al. Gene expression profiling predicts clinical outcome of breast cancer. Nature 415, 530–536 (2002).

    Article  CAS  Google Scholar 

  95. Spellman, P.T. et al. Comprehensive identification of cell cycle-regulated genes of the yeast Saccharomyces cerevisiae by microarray hybridization. Mol. Biol. Cell 9, 3273–3297 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Hughes, T.R. et al. Functional discovery via a compendium of expression profiles. Cell 102, 109–126 (2000).

    Article  CAS  PubMed  Google Scholar 

  97. Roberts, C.J. et al. Signaling and circuitry of multiple MAPK pathways revealed by a matrix of global gene expression profiles. Science 287, 873–880 (2000).

    Article  CAS  PubMed  Google Scholar 

  98. Eisen, M.B., Spellman, P.T., Brown, P.O. & Botstein, D. Cluster analysis and display of genome-wide expression patterns. Proc. Natl. Acad. Sci. USA 95, 14863–14868 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Alter, O., Brown, P.O. & Botstein, D. Singular value decomposition for genome-wide expression data processing and modeling. Proc. Natl. Acad. Sci. USA 97, 10101–10106 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Ideker, T. et al. Integrated genomic and proteomic analyses of a systematically perturbed metabolic network. Science 292, 929–934 (2001).

    Article  CAS  PubMed  Google Scholar 

  101. Anderson, L. & Seilhamer, J. A comparison of selected mRNA and protein abundances in human liver. Electrophoresis 18, 533–537 (1997).

    Article  CAS  PubMed  Google Scholar 

  102. Futcher, B., Latter, G.I., Monardo, P., McLaughlin, C.S. & Garrels, J.I. A sampling of the yeast proteome. Mol. Cell. Biol. 19, 7357–7368 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Betts, J.C., Lukey, P.T., Robb, L.C., McAdam, R.A. & Duncan, K. Evaluation of a nutrient starvation model of Mycobacterium tuberculosis persistence by gene and protein expression profiling. Mol. Microbiol. 43, 717–731 (2002).

    Article  CAS  PubMed  Google Scholar 

  104. Griffin, T.J. et al. Complementary profiling of gene expression at the transcriptome and proteome levels in Saccharomyces cerevisiae. Mol. Cell. Proteomics 1, 323–333 (2002).

    Article  CAS  PubMed  Google Scholar 

  105. Adam, G.C., Cravatt, B.F. & Sorensen, E.J. Profiling the specific reactivity of the proteome with non-directed activity-based probes. Chem. Biol. 8, 81–95 (2001).

    Article  CAS  PubMed  Google Scholar 

  106. Adam, G.C., Sorensen, E.J. & Cravatt, B.F. Proteomic profiling of mechanistically distinct enzyme classes using a common chemotype. Nat. Biotechnol. 20, 805–809 (2002).

    Article  CAS  PubMed  Google Scholar 

  107. Greenbaum, D., Medzihradszky, K.F., Burlingame, A. & Bogyo, M. Epoxide electrophiles as activity-dependent cysteine protease profiling and discovery tools. Chem. Biol. 7, 569–581 (2000).

    Article  CAS  PubMed  Google Scholar 

  108. Lopez-Otin, C. & Overall, C.M. Protease degradomics: a new challenge for proteomics. Nat. Rev. Mol. Cell Biol. 3, 509–519 (2002).

    Article  CAS  PubMed  Google Scholar 

  109. Bogyo, M., Shin, S., McMaster, J.S. & Ploegh, H.L. Substrate binding and sequence preference of the proteasome revealed by active-site-directed affinity probes. Chem. Biol. 5, 307–320 (1998).

    Article  CAS  PubMed  Google Scholar 

  110. Cravatt, B.F. & Sorensen, E.J. Chemical strategies for the global analysis of protein function. Curr. Opin. Chem. Biol. 4, 663–668 (2000).

    Article  CAS  PubMed  Google Scholar 

  111. Greenbaum, D. et al. Chemical approaches for functionally probing the proteome. Mol. Cell. Proteomics 1, 60–68 (2002).

    Article  CAS  PubMed  Google Scholar 

  112. Kidd, D., Liu, Y. & Cravatt, B.F. Profiling serine hydrolase activities in complex proteomes. Biochemistry 40, 4005–4015 (2001).

    Article  CAS  PubMed  Google Scholar 

  113. Liu, Y., Patricelli, M.P. & Cravatt, B.F. Activity-based protein profiling: the serine hydrolases. Proc. Natl. Acad. Sci. USA 96, 14694–14699 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Withers, S.G. & Aebersold, R. Approaches to labeling and identification of active-site residues in glycosidases. Protein Sci. 4, 361–372 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Haystead, C.M., Gregory, P., Sturgill, T.W. & Haystead, T.A. γ-Phosphate-linked ATP-sepharose for the affinity purification of protein kinases. Rapid purification to homogeneity of skeletal muscle mitogen-activated protein kinase kinase. Eur. J. Biochem. 214, 459–467 (1993).

    Article  CAS  PubMed  Google Scholar 

  116. Turecek, F. Mass spectrometry in coupling with affinity capture-release and isotope-coded affinity tags for quantitative protein analysis. J. Mass Spectrom. 37, 1–14 (2002).

    Article  CAS  PubMed  Google Scholar 

  117. Kumazaki, T., Terasawa, K. & Ishii, S. Affinity chromatography on immobilized anhydrotrypsin: general utility for selective isolation of C-terminal peptides from protease digests of proteins. J. Biochem. 102, 1539–1546 (1987).

    Article  CAS  PubMed  Google Scholar 

  118. Fricker, L.D. et al. Identification and characterization of proSAAS, a granin-like neuroendocrine peptide precursor that inhibits prohormone processing. J. Neurosci. 20, 639–648 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Bures, E.J. et al. Identification of incompletely processed potential carboxypeptidase E substrates from CpEfat/CpEfat mice. Proteomics 1, 79–92 (2001).

    Article  CAS  PubMed  Google Scholar 

  120. Flint, A.J., Tiganis, T., Barford, D. & Tonks, N.K. Development of 'substrate-trapping' mutants to identify physiological substrates of protein tyrosine phosphatases. Proc. Natl. Acad. Sci. USA 94, 1680–1685 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Zhang, S.H., Liu, J., Kobayashi, R. & Tonks, N.K. Identification of the cell cycle regulator VCP (p97/CDC48) as a substrate of the band 4.1-related protein-tyrosine phosphatase PTPH1. J. Biol. Chem. 274, 17806–17812 (1999).

    Article  CAS  PubMed  Google Scholar 

  122. Belew, M. & Porath, J. Immobilized metal ion affinity chromatography. Effect of solute structure, ligand density and salt concentration on the retention of peptides. J. Chromatogr. 516, 333–354 (1990).

    Article  CAS  PubMed  Google Scholar 

  123. Posewitz, M.C. & Tempst, P. Immobilized gallium(iii) affinity chromatography of phosphopeptides. Anal. Chem. 71, 2883–2892 (1999).

    Article  CAS  PubMed  Google Scholar 

  124. Oda, Y., Nagasu, T. & Chait, B.T. Enrichment analysis of phosphorylated proteins as a tool for probing the phosphoproteome. Nat. Biotechnol. 19, 379–382 (2001).

    Article  CAS  PubMed  Google Scholar 

  125. Goshe, M.B. et al. Phosphoprotein isotope-coded affinity tag approach for isolating and quantitating phosphopeptides in proteome-wide analyses. Anal. Chem. 73, 2578–2586 (2001).

    Article  CAS  PubMed  Google Scholar 

  126. Zhou, H., Watts, J.D. & Aebersold, R. A systematic approach to the analysis of protein phosphorylation. Nat. Biotechnol. 19, 375–378 (2001).

    Article  CAS  PubMed  Google Scholar 

  127. Pandey, A. & Mann, M. Proteomics to study genes and genomes. Nature 405, 837–846 (2000).

    Article  CAS  PubMed  Google Scholar 

  128. Deshaies, R.J. et al. Charting the protein complexome in yeast by mass spectrometry. Mol. Cell. Proteomics 1, 3–10 (2002).

    Article  CAS  PubMed  Google Scholar 

  129. Hartwell, L.H., Hopfield, J.J., Leibler, S. & Murray, A.W. From molecular to modular cell biology. Nature 402, C47–C52 (1999).

    Article  CAS  PubMed  Google Scholar 

  130. Gavin, A.C. et al. Functional organization of the yeast proteome by systematic analysis of protein complexes. Nature 415, 141–147 (2002).

    Article  CAS  PubMed  Google Scholar 

  131. Ho, Y. et al. Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry. Nature 415, 180–183 (2002).

    Article  CAS  PubMed  Google Scholar 

  132. von Mering, C. et al. Comparative assessment of large-scale data sets of protein-protein interactions. Nature 417, 399–403 (2002).

    Article  CAS  PubMed  Google Scholar 

  133. Ranish, J.A. et al. The study of macromolecular complexes by quantitative proteomics. Nat. Genet. (in the press).

  134. Pease, A.C. et al. Light-generated oligonucleotide arrays for rapid DNA sequence analysis. Proc. Natl. Acad. Sci. USA 91, 5022–5026 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Hughes, T.R. et al. Expression profiling using microarrays fabricated by an ink-jet oligonucleotide synthesizer. Nat. Biotechnol. 19, 342–347 (2001).

    Article  CAS  PubMed  Google Scholar 

  136. van Berkum, N.L. & Holstege, F.C. DNA microarrays: raising the profile. Curr. Opin. Biotechnol. 12, 48–52 (2001).

    Article  CAS  PubMed  Google Scholar 

  137. Nadon, R. & Shoemaker, J. Statistical issues with microarrays: processing and analysis. Trends Genet. 18, 265–271 (2002).

    Article  CAS  PubMed  Google Scholar 

  138. Haab, B.B., Dunham, M.J. & Brown, P.O. Protein microarrays for highly parallel detection and quantitation of specific proteins and antibodies in complex solutions. Genome Biol. 2, RESEARCH0004 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Jenkins, R.E. & Pennington, S.R. Arrays for protein expression profiling: towards a viable alternative to two-dimensional gel electrophoresis? Proteomics 1, 13–29 (2001).

    Article  CAS  PubMed  Google Scholar 

  140. Zhou, H., Roy, S., Schulman, H. & Natan, M.J. Solution and chip arrays in protein profiling. Trends Biotechnol. 19, S34–S39 (2001).

    Article  CAS  PubMed  Google Scholar 

  141. McCafferty, J., Griffiths, A.D., Winter, G. & Chiswell, D.J. Phage antibodies: filamentous phage displaying antibody variable domains. Nature 348, 552–554 (1990).

    Article  CAS  PubMed  Google Scholar 

  142. Tramontano, A. et al. The making of the minibody: an engineered β-protein for the display of conformationally constrained peptides. J. Mol. Recognit. 7, 9–24 (1994).

    Article  CAS  PubMed  Google Scholar 

  143. Martin, F. et al. Coupling protein design and in vitro selection strategies: improving specificity and affinity of a designed β-protein IL-6 antagonist. J. Mol. Biol. 255, 86–97 (1996).

    Article  CAS  PubMed  Google Scholar 

  144. Koivunen, E., Wang, B. & Ruoslahti, E. Phage libraries displaying cyclic peptides with different ring sizes: ligand specificities of the RGD-directed integrins. Biotechnology 13, 265–270 (1995).

    CAS  PubMed  Google Scholar 

  145. McConnell, S.J. & Hoess, R.H. Tendamistat as a scaffold for conformationally constrained phage peptide libraries. J. Mol. Biol. 250, 460–470 (1995).

    Article  CAS  PubMed  Google Scholar 

  146. Nord, K., Nilsson, J., Nilsson, B., Uhlen, M. & Nygren, P.A. A combinatorial library of an α-helical bacterial receptor domain. Protein Eng. 8, 601–608 (1995).

    Article  CAS  PubMed  Google Scholar 

  147. Choo, Y. & Klug, A. Designing DNA-binding proteins on the surface of filamentous phage. Curr. Opin. Biotechnol. 6, 431–436 (1995).

    Article  CAS  PubMed  Google Scholar 

  148. Brody, E.N. et al. The use of aptamers in large arrays for molecular diagnostics. Mol. Diagn. 4, 381–388 (1999).

    Article  CAS  PubMed  Google Scholar 

  149. Holt, L.J., Enever, C., de Wildt, R.M. & Tomlinson, I.M. The use of recombinant antibodies in proteomics. Curr. Opin. Biotechnol. 11, 445–449 (2000).

    Article  CAS  PubMed  Google Scholar 

  150. Eklund, M., Axelsson, L., Uhlen, M. & Nygren, P.A. Anti-idiotypic protein domains selected from protein A-based affibody libraries. Proteins 48, 454–462 (2002).

    Article  CAS  PubMed  Google Scholar 

  151. Mitchell, P. A perspective on protein microarrays. Nat. Biotechnol. 20, 225–229 (2002).

    Article  CAS  PubMed  Google Scholar 

  152. Cahill, D.J. Protein and antibody arrays and their medical applications. J. Immunol. Methods 250, 81–91 (2001).

    Article  CAS  PubMed  Google Scholar 

  153. Walter, G., Bussow, K., Cahill, D., Lueking, A. & Lehrach, H. Protein arrays for gene expression and molecular interaction screening. Curr. Opin. Microbiol. 3, 298–302 (2000).

    Article  CAS  PubMed  Google Scholar 

  154. Schweitzer, B. et al. Multiplexed protein profiling on microarrays by rolling-circle amplification. Nat. Biotechnol. 20, 359–365 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Houseman, B.T. & Mrksich, M. Towards quantitative assays with peptide chips: a surface engineering approach. Trends Biotechnol. 20, 279–281 (2002).

    Article  CAS  PubMed  Google Scholar 

  156. Martzen, M.R. et al. A biochemical genomics approach for identifying genes by the activity of their products. Science 286, 1153–1155 (1999).

    Article  CAS  PubMed  Google Scholar 

  157. Houseman, B.T., Huh, J.H., Kron, S.J. & Mrksich, M. Peptide chips for the quantitative evaluation of protein kinase activity. Nat. Biotechnol. 20, 270–274 (2002).

    Article  CAS  PubMed  Google Scholar 

  158. Zhu, H. et al. Analysis of yeast protein kinases using protein chips. Nat. Genet. 26, 283–289 (2000).

    Article  CAS  PubMed  Google Scholar 

  159. Ren, B. et al. Genome-wide location and function of DNA binding proteins. Science 290, 2306–2309 (2000).

    Article  CAS  PubMed  Google Scholar 

  160. Krylov, A.S., Zasedateleva, O.A., Prokopenko, D.V., Rouviere-Yaniv, J. & Mirzabekov, A.D. Massive parallel analysis of the binding specificity of histone-like protein HU to single- and double-stranded DNA with generic oligodeoxyribonucleotide microchips. Nucleic Acids Res. 29, 2654–2660 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. MacBeath, G. & Schreiber, S.L. Printing proteins as microarrays for high-throughput function determination. Science 289, 1760–1763 (2000).

    CAS  PubMed  Google Scholar 

  162. Diehn, M., Eisen, M.B., Botstein, D. & Brown, P.O. Large-scale identification of secreted and membrane-associated gene products using DNA microarrays. Nat. Genet. 25, 58–62 (2000).

    Article  CAS  PubMed  Google Scholar 

  163. Zong, Q., Schummer, M., Hood, L. & Morris, D.R. Messenger RNA translation state: the second dimension of high-throughput expression screening. Proc. Natl. Acad. Sci. USA 96, 10632–10636 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Lee, K.B., Park, S.J., Mirkin, C.A., Smith, J.C. & Mrksich, M. Protein nanoarrays generated by dip-pen nanolithography. Science 295, 1702–1705 (2002).

    Article  CAS  PubMed  Google Scholar 

  165. Winzeler, E.A. et al. Functional characterization of the S. cerevisiae genome by gene deletion and parallel analysis. Science 285, 901–906 (1999).

    Article  CAS  PubMed  Google Scholar 

  166. Fields, S. & Song, O. A novel genetic system to detect protein-protein interactions. Nature 340, 245–246 (1989).

    Article  CAS  PubMed  Google Scholar 

  167. Tucker, C.L., Gera, J.F. & Uetz, P. Towards an understanding of complex protein networks. Trends Cell Biol. 11, 102–106 (2001).

    Article  CAS  PubMed  Google Scholar 

  168. Bartel, P.L., Roecklein, J.A., SenGupta, D. & Fields, S. A protein linkage map of Escherichia coli bacteriophage T7. Nat. Genet. 12, 72–77 (1996).

    Article  CAS  PubMed  Google Scholar 

  169. McCraith, S., Holtzman, T., Moss, B. & Fields, S. Genome-wide analysis of vaccinia virus protein-protein interactions. Proc. Natl. Acad. Sci. USA 97, 4879–4884 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Uetz, P. et al. A comprehensive analysis of protein-protein interactions in Saccharomyces cerevisiae. Nature 403, 623–627 (2000).

    Article  CAS  PubMed  Google Scholar 

  171. Ito, T. et al. Toward a protein-protein interaction map of the budding yeast: A comprehensive system to examine two-hybrid interactions in all possible combinations between the yeast proteins. Proc. Natl. Acad. Sci. USA 97, 1143–1147 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Ito, T. et al. A comprehensive two-hybrid analysis to explore the yeast protein interactome. Proc. Natl. Acad. Sci. USA 98, 4569–4574 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  173. Rain, J.C. et al. The protein-protein interaction map of Helicobacter pylori. Nature 409, 211–215 (2001).

    Article  CAS  PubMed  Google Scholar 

  174. Walhout, A.J. et al. Protein interaction mapping in C. elegans using proteins involved in vulval development. Science 287, 116–122 (2000).

    Article  CAS  PubMed  Google Scholar 

  175. Davy, A. et al. A protein-protein interaction map of the Caenorhabditis elegans 26S proteasome. EMBO Rep. 2, 821–828 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. Zhang, B., Kraemer, B., SenGupta, D., Fields, S. & Wickens, M. Yeast three-hybrid system to detect and analyze RNA-protein interactions. Methods Enzymol. 318, 399–419 (2000).

    Article  CAS  PubMed  Google Scholar 

  177. Tucker, C.L. & Fields, S. A yeast sensor of ligand binding. Nat. Biotechnol. 19, 1042–1046 (2001).

    Article  CAS  PubMed  Google Scholar 

  178. Heim, R., Prasher, D.C. & Tsien, R.Y. Wavelength mutations and posttranslational autoxidation of green fluorescent protein. Proc. Natl. Acad. Sci. USA 91, 12501–12504 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Tsien, R.Y. The green fluorescent protein. Annu. Rev. Biochem. 67, 509–544 (1998).

    Article  CAS  PubMed  Google Scholar 

  180. Tsien, R.Y. & Miyawaki, A. Seeing the machinery of live cells. Science 280, 1954–1955 (1998).

    Article  CAS  PubMed  Google Scholar 

  181. Kumar, A. et al. Subcellular localization of the yeast proteome. Genes Dev. 16, 707–719 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  182. Garrels, J.I. YPD—a database for the proteins of Saccharomyces cerevisiae. Nucleic Acids Res. 24, 46–49 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  183. Cherry, J.M. et al. SGD: Saccharomyces Genome Database. Nucleic Acids Res. 26, 73–79 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  184. Shiio, Y. et al. Quantitative proteomic analysis of Myc oncoprotein function. EMBO J. 21, 5088–5096 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  185. Guina, T. et al. Quantitative proteomic analysis of Pseudomonas aeruginosa indicates synthesis of quinolone signal in adaptation to cystic fibrosis airways. Proc. Natl. Acad. Sci. USA (in the press).

  186. Ewing, B., Hillier, L., Wendl, M.C. & Green, P. Base-calling of automated sequencer traces using phred. I. Accuracy assessment. Genome Res. 8, 175–185 (1998).

    Article  CAS  PubMed  Google Scholar 

  187. Ewing, B. & Green, P. Base-calling of automated sequencer traces using phred. II. Error probabilities. Genome Res. 8, 186–194 (1998).

    Article  CAS  PubMed  Google Scholar 

  188. Keller, A. et al. Experimental protein mixture for validating tandem mass spectral analysis. Omics 6, 207–212 (2002).

    Article  CAS  PubMed  Google Scholar 

  189. Caprioli, R.M., Farmer, T.B. & Gile, J. Molecular imaging of biological samples: localization of peptides and proteins using MALDI-TOF MS. Anal. Chem. 69, 4751–4760 (1997).

    Article  CAS  PubMed  Google Scholar 

  190. Stoeckli, M., Chaurand, P., Hallahan, D.E. & Caprioli, R.M. Imaging mass spectrometry: a new technology for the analysis of protein expression in mammalian tissues. Nat. Med. 7, 493–496 (2001).

    Article  CAS  PubMed  Google Scholar 

  191. Collings, B.A., Sudakov, M. & Londry, F.A. Resonance shifts in the excitation of the n = 0, K = 1 to 6 quadrupolar resonances for ions confined in a linear ion trap. J. Am. Soc. Mass Spectrom. 13, 577–586 (2002).

    Article  CAS  PubMed  Google Scholar 

  192. Medzihradszky, K.F. et al. The characteristics of peptide collision-induced dissociation using a high-performance MALDI-TOF/TOF tandem mass spectrometer. Anal. Chem. 72, 552–558 (2000).

    Article  CAS  PubMed  Google Scholar 

  193. Marshall, A.G., Hendrickson, C.L. & Jackson, G.S. Fourier transform ion cyclotron resonance mass spectrometry: a primer. Mass Spectrom. Rev. 17, 1–35 (1998).

    Article  CAS  PubMed  Google Scholar 

  194. Ullrich, B., Ushkaryov, Y.A. & Sudhof, T.C. Cartography of neurexins: more than 1000 isoforms generated by alternative splicing and expressed in distinct subsets of neurons. Neuron 14, 497–507 (1995).

    Article  CAS  PubMed  Google Scholar 

  195. Petricoin, E.F. et al. Use of proteomic patterns in serum to identify ovarian cancer. Lancet 359, 572–577 (2002).

    Article  CAS  PubMed  Google Scholar 

  196. Adam, B.L. et al. Serum protein fingerprinting coupled with a pattern-matching algorithm distinguishes prostate cancer from benign prostate hyperplasia and healthy men. Cancer Res. 62, 3609–3614 (2002).

    CAS  PubMed  Google Scholar 

  197. Alon, U., Surette, M.G., Barkai, N. & Leibler, S. Robustness in bacterial chemotaxis. Nature 397, 168–171 (1999).

    Article  CAS  PubMed  Google Scholar 

  198. Guet, C.C., Elowitz, M.B., Hsing, W. & Leibler, S. Combinatorial synthesis of genetic networks. Science 296, 1466–1470 (2002).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We would like to thank L. Feltz for administrative assistance and J. Watts for review of the manuscript.

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    Present address: Farmal Biomedicines, LLC, 129 North Hill Avenue, Suite #107, Pasadena, California, 91106, USA

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    Scott D. Patterson

  2. Institute for Systems Biology, 1441 North 34th Street, Seattle, 98103, Washington, USA

    Ruedi H. Aebersold

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Patterson, S., Aebersold, R. Proteomics: the first decade and beyond. Nat Genet 33 (Suppl 3), 311–323 (2003). https://doi.org/10.1038/ng1106

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