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Mass spectrometry–based functional proteomics: from molecular machines to protein networks

Nature Methods volume 4, pages 807–815 (2007)Cite this article

Abstract

The study of protein-protein interactions by mass spectrometry is an increasingly important part of post-genomics strategies to understand protein function. A variety of mass spectrometry–based approaches allow characterization of cellular protein assemblies under near-physiological conditions and subsequent assignment of individual proteins to specific molecular machines, pathways and networks, according to an increasing level of organizational complexity. An appropriate analytical strategy can be individually tailored—from an in-depth analysis of single complexes to a large-scale characterization of entire molecular pathways or even an analysis of the molecular organization of entire expressed proteomes. Here we review different options regarding protein-complex purification strategies, mass spectrometry analysis and bioinformatic methods according to the specific question that is being addressed.

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Figure 1: Decision tree of options for the most common different protein-protein (or protein-ligand) interaction experimental strategies.

Katie Ris-Vicari

Figure 2: Main routes of protein-complex purification.

Katie Ris-Vicari

Figure 3: Flowchart of different options for sample preparation, protein separation and mass-spectrometric analysis.

Katie Ris-Vicari

Figure 4: Illustration of the types of protein networks that can be elucidated with different experimental approaches.

Katie Ris-Vicari

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References

  1. Steen, H. & Mann, M. The ABC's (and XYZ's) of peptide sequencing. Nat. Rev. Mol. Cell Biol. 5, 699–711 (2004).

    Article  CAS  PubMed  Google Scholar 

  2. Ferguson, P.L. & Smith, R.D. Proteome analysis by mass spectrometry. Annu. Rev. Biophys. Biomol. Struct. 32, 399–424 (2003).

    Article  CAS  PubMed  Google Scholar 

  3. Bouwmeester, T. et al. A physical and functional map of the human TNF-alpha NF-kappa B signal transduction pathway. Nat. Cell Bio. 6, 97–105 (2004).

    Article  CAS  Google Scholar 

  4. Blagoev, B. et al. A proteomics strategy to elucidate functional protein-protein interactions applied to EGF signaling. Nat. Biotechnol. 21, 315–318 (2003).

    Article  CAS  PubMed  Google Scholar 

  5. Major, M.B. et al. Wilms tumor suppressor WTX negatively regulates WNT/beta-catenin signaling. Science 316, 1043–1046 (2007).

    Article  CAS  PubMed  Google Scholar 

  6. Weston, A.D. & Hood, L. Systems biology, proteomics, and the future of health care: Toward predictive, preventative, and personalized medicine. J. Proteome Res. 3, 179–196 (2004).

    Article  CAS  PubMed  Google Scholar 

  7. Anderson, N.L. & Anderson, N.G. The human plasma proteome — history, character, and diagnostic prospects. Mol. Cell. Proteomics 1, 845–867 (2002).

    Article  CAS  PubMed  Google Scholar 

  8. 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 

  9. 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 

  10. Riedel, C.G. et al. Protein phosphatase 2A protects centromeric sister chromatid cohesion during meiosis I. Nature 441, 53–61 (2006).

    Article  CAS  PubMed  Google Scholar 

  11. Vanacova, S. et al. A new yeast poly(A) polymerase complex involved in RNA quality control. PLoS Biol. 3, 986–997 (2005).

    Article  CAS  Google Scholar 

  12. Bertwistle, D., Sugimoto, M. & Sherr, C.J. Physical and functional interactions of the Arf tumor suppressor protein with nucleophosmin/B23. Mol. Cell. Biol. 24, 985–996 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Lorentzen, E. et al. The archaeal exosome core is a hexameric ring structure with three catalytic subunits. Nat. Struct. Mol. Biol. 12, 575–581 (2005).

    Article  CAS  PubMed  Google Scholar 

  14. Hao, B., Oehlmann, S., Sowa, M.E., Harper, J.W. & Pavletich, N.P. Structure of a Fbw7-Skp1-cyclin E complex: multisite-phosphorylated substrate recognition by SCF ubiquitin ligases. Mol. Cell 26, 131–143 (2007).

    Article  CAS  PubMed  Google Scholar 

  15. Nickell, S., Kofler, C., Leis, A.P. & Baumeister, W. A visual approach to proteomics. Nat. Rev. Mol. Cell Biol. 7, 225–230 (2006).

    Article  CAS  PubMed  Google Scholar 

  16. Groll, M., Bochtler, M., Brandstetter, H., Clausen, T. & Huber, R. Molecular machines for protein degradation. ChemBioChem 6, 222–256 (2005).

    Article  CAS  PubMed  Google Scholar 

  17. Gorg, A., Weiss, W. & Dunn, M.J. Current two-dimensional electrophoresis technology for proteomics. Proteomics 4, 3665–3685 (2004).

    Article  PubMed  CAS  Google Scholar 

  18. Wulfkuhle, J.D. et al. Proteomics of human breast ductal carcinoma in situ. Cancer Res. 62, 6740–6749 (2002).

    CAS  PubMed  Google Scholar 

  19. Le Naour, F. et al. Profiling changes in gene expression during differentiation and maturation of monocyte-derived dendritic cells using both oligonucleotide microarrays and proteomics. J. Biol. Chem. 276, 17920–17931 (2001).

    Article  CAS  PubMed  Google Scholar 

  20. Ong, S.E. & Mann, M. Mass spectrometry-based proteomics turns quantitative. Nat. Chem. Biol. 1, 252–262 (2005).

    Article  CAS  PubMed  Google Scholar 

  21. Zhang, H., Yan, W. & Aebersold, R. Chemical probes and tandem mass spectrometry: a strategy for the quantitative analysis of proteomes and subproteomes. Curr. Opin. Chem. Biol. 8, 66–75 (2004).

    Article  CAS  PubMed  Google Scholar 

  22. Jensen, O.N. Modification-specific proteomics: characterization of post-translational modifications by mass spectrometry. Curr. Opin. Chem. Biol. 8, 33–41 (2004).

    Article  PubMed  CAS  Google Scholar 

  23. Mann, M. & Jensen, O.N. Proteomic analysis of post-translational modifications. Nat. Biotechnol. 21, 255–261 (2003).

    Article  CAS  PubMed  Google Scholar 

  24. 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 

  25. Ghaemmaghami, S. et al. Global analysis of protein expression in yeast. Nature 425, 737–741 (2003).

    Article  CAS  PubMed  Google Scholar 

  26. Alberts, B. The cell as a collection of protein machines: preparing the next generation of molecular biologists. Cell 92, 291–294 (1998).

    Article  CAS  PubMed  Google Scholar 

  27. Terpe, K. Overview of tag protein fusions: from molecular and biochemical fundamentals to commercial systems. Appl. Microbiol. Biotechnol. 60, 523–533 (2003).

    Article  CAS  PubMed  Google Scholar 

  28. Bauch, A. & Superti-Furga, G. Charting protein complexes, signaling pathways, and networks in the immune system. Immunol. Rev. 210, 187–207 (2006).

    Article  CAS  PubMed  Google Scholar 

  29. Zhu, H. & Snyder, M. Protein chip technology. Curr. Opin. Chem. Biol. 7, 55–63 (2003).

    Article  CAS  PubMed  Google Scholar 

  30. Chien, C.T., Bartel, P.L., Sternglanz, R. & Fields, S. The 2-hybrid system — a method to identify and clone genes for proteins that interact with a protein of interest. Proc. Natl. Acad. Sci. USA 88, 9578–9582 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Giepmans, B.N.G., Adams, S.R., Ellisman, M.H. & Tsien, R.Y. The fluorescent toolbox for assessing protein location and function. Science 312, 217–224 (2006).

    Article  CAS  PubMed  Google Scholar 

  32. Barrios-Rodiles, M. et al. High-throughput mapping of a dynamic signaling network in mammalian cells. Science 307, 1621–1625 (2005).

    Article  CAS  PubMed  Google Scholar 

  33. Aloy, P. & Russell, R.B. Structural systems biology: modelling protein interactions. Nat. Rev. Mol. Cell Biol. 7, 188–197 (2006).

    Article  CAS  PubMed  Google Scholar 

  34. Marcotte, E.M. et al. Detecting protein function and protein-protein interactions from genome sequences. Science 285, 751–753 (1999).

    Article  CAS  PubMed  Google Scholar 

  35. Tornow, S. & Mewes, H.W. Functional modules by relating protein interaction networks and gene expression. Nucleic Acids Res. 31, 6283–6289 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Sharan, R. & Ideker, T. Modeling cellular machinery through biological network comparison. Nat. Biotechnol. 24, 427–433 (2006).

    Article  CAS  PubMed  Google Scholar 

  37. Ranish, J.A. et al. The study of macromolecular complexes by quantitative proteomics. Nat. Genet. 33, 349–355 (2003).

    Article  CAS  PubMed  Google Scholar 

  38. Mann, M. Functional and quantitative proteomics using SILAC. Nat. Rev. Mol. Cell Biol. 7, 952–958 (2006).

    Article  CAS  PubMed  Google Scholar 

  39. Hochleitner, E.O. et al. Protein stoichiometry of a multiprotein complex, the human spliceosomal U1 small nuclear ribonucleoprotein — absolute quantification using isotope-coded tags and mass spectrometry. J. Biol. Chem. 280, 2536–2542 (2005).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  41. Aebersold, R. & Mann, M. Mass spectrometry–based proteomics. Nature 422, 198–207 (2003).

    Article  CAS  PubMed  Google Scholar 

  42. Fishman, M.C. & Porter, J.A. Pharmaceuticals—a new grammar for drug discovery. Nature 437, 491–493 (2005).

    Article  CAS  PubMed  Google Scholar 

  43. Rodi, D.J. & Makowski, L. Phage-display technology—finding a needle in a vast molecular haystack. Curr. Opin. Biotechnol. 10, 87–93 (1999).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  45. Zhu, H. et al. Global analysis of protein activities using proteome chips. Science 293, 2101–2105 (2001).

    Article  CAS  PubMed  Google Scholar 

  46. Paweletz, C.P. et al. Reverse phase protein microarrays which capture disease progression show activation of pro-survival pathways at the cancer invasion front. Oncogene 20, 1981–1989 (2001).

    Article  CAS  PubMed  Google Scholar 

  47. Huang, R.P., Huang, R.C., Fan, Y. & Lin, Y. Simultaneous detection of multiple cytokines from conditioned media and patient's sera by an antibody-based protein array system. Anal. Biochem. 294, 55–62 (2001).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  49. Hamelinck, D. et al. Optimized normalization for antibody microarrays and application to serum-protein profiling. Mol. Cell. Proteomics 4, 773–784 (2005).

    Article  CAS  PubMed  Google Scholar 

  50. Davies, H., Lomas, L. & Austen, B. Profiling of amyloid beta peptide variants using SELDI ProteinChip (R) arrays. Biotechniques 27, 1258–1261 (1999).

    CAS  PubMed  Google Scholar 

  51. Hua, S., To, W.Y., Nguyen, T.T., Wong, M.L. & Wang, C.C. Purification and characterization of proteasomes from Trypanosoma brucei. Mol. Biochem. Parasitol. 78, 33–46 (1996).

    Article  CAS  PubMed  Google Scholar 

  52. Huang, L. et al. Functional assignment of the 20S proteasome from Trypanosoma brucei using mass spectrometry and new bioinformatics approaches. J. Biol. Chem. 276, 28327–28339 (2001).

    Article  CAS  PubMed  Google Scholar 

  53. Harlow, E. & Lane, D. Antibodies: a Laboratory Manual (Cold Spring Harbor Laboratory Press, Cold Springs Harbor, New York, 1988).

    Google Scholar 

  54. Uhlen, M. & Ponten, F. Antibody-based proteomics for human tissue profiling. Mol. Cell. Proteomics 4, 384–393 (2005).

    Article  CAS  PubMed  Google Scholar 

  55. Nord, K. et al. Binding proteins selected from combinatorial libraries of an alpha-helical bacterial receptor domain. Nat. Biotechnol. 15, 772–777 (1997).

    Article  CAS  PubMed  Google Scholar 

  56. Hermann, T. & Patel, D.J. Biochemistry - Adaptive recognition by nucleic acid aptamers. Science 287, 820–825 (2000).

    Article  CAS  PubMed  Google Scholar 

  57. Waugh, D.S. Making the most of affinity tags. Trends Biotechnol. 23, 316–320 (2005).

    Article  CAS  PubMed  Google Scholar 

  58. de Boer, E. et al. Efficient biotinylation and single-step purification of tagged transcription factors in mammalian cells and transgenic mice. Proc. Natl. Acad. Sci. USA 100, 7480–7485 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Neubauer, G. et al. Identification of the proteins of the yeast U1 small nuclear ribonucleoprotein complex by mass spectrometry. Proc. Natl. Acad. Sci. USA 94, 385–390 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Puig, O. et al. The tandem affinity purification (TAP) method: A general procedure of protein complex purification. Methods 24, 218–229 (2001).

    Article  CAS  PubMed  Google Scholar 

  61. Rigaut, G. et al. A generic protein purification method for protein complex characterization and proteome exploration. Nat. Biotechnol. 17, 1030–1032 (1999).

    Article  CAS  PubMed  Google Scholar 

  62. Burckstummer, T. et al. An efficient tandem affinity purification procedure for interaction proteomics in mammalian cells. Nat. Methods 3, 1013–1019 (2006).

    Article  PubMed  CAS  Google Scholar 

  63. Forler, D. et al. An efficient protein complex purification method for functional proteomics in higher eukaryotes. Nat. Biotechnol. 21, 89–92 (2003).

    Article  CAS  PubMed  Google Scholar 

  64. Drakas, R., Prisco, M. & Baserga, R. A modified tandem affinity purification tag technique for the purification of protein complexes in mammalian cells. Proteomics 5, 132–137 (2005).

    Article  CAS  PubMed  Google Scholar 

  65. Knuesel, M. et al. Identification of novel protein-protein interactions using a versatile mammalian tandem affinity purification expression system. Mol. Cell. Proteomics 2, 1225–1233 (2003).

    Article  CAS  PubMed  Google Scholar 

  66. Westermarck, J. et al. The DEXD/H-box RNA helicase RHII/Gu is a co-factor for c-Jun-activated transcription. EMBO J. 21, 451–460 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Gavin, A.C. & Superti-Furga, G. Protein complexes and proteome organization from yeast to man. Curr. Opin. Chem. Biol. 7, 21–27 (2003).

    Article  CAS  PubMed  Google Scholar 

  68. Benesch, J.L.P., Aquilina, J.A., Ruotolo, B.T., Sobott, F. & Robinson, C.V. Tandem mass spectrometry reveals the quaternary organization of macromolecular assemblies. Chem. Biol. 13, 597–605 (2006).

    Article  CAS  PubMed  Google Scholar 

  69. Kelleher, N.L. et al. Top down versus bottom up protein characterization by tandem high-resolution mass spectrometry. J. Am. Chem. Soc. 121, 806–812 (1999).

    Article  CAS  Google Scholar 

  70. Benjamin, D.R., Robinson, C.V., Hendrick, J.P., Hartl, F.U. & Dobson, C.M. Mass spectrometry of ribosomes and ribosomal subunits. Proc. Natl. Acad. Sci. USA 95, 7391–7395 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Sharon, M., Taverner, T., Ambroggio, X.I., Deshaies, R.J. & Robinson, C.V. Structural organization of the 19S proteasome lid: Insights from MS of intact complexes. PLoS Biol. 4, 1314–1323 (2006).

    Article  CAS  Google Scholar 

  72. Hernandez, H., Dziembowski, A., Taverner, T., Seraphin, B. & Robinson, C.V. Subunit architecture of multimeric complexes isolated directly from cells. EMBO Rep. 7, 605–610 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Rappsilber, J., Siniossoglou, S., Hurt, E.C. & Mann, M. A generic strategy to analyze the spatial organization of multi-protein complexes by cross-linking and mass spectrometry. Anal. Chem. 72, 267–275 (2000).

    Article  CAS  PubMed  Google Scholar 

  74. Vasilescu, J., Guo, X.C. & Kast, J. Identification of protein-protein interactions using in vivo cross-linking and mass spectrometry. Proteomics 4, 3845–3854 (2004).

    Article  CAS  PubMed  Google Scholar 

  75. Shevchenko, A., Tomas, H., Havlis, J., Olsen, J. V. & Mann, M. In-gel digestion for mass spectrometric characterization of proteins and proteomes. Nat. Protoc. 1, 2856–2860 (2006).

    Article  CAS  PubMed  Google Scholar 

  76. Havlis, J. & Shevchenko, A. Absolute quantification of proteins in solutions and in polyacrylamide gels by mass spectrometry. Anal. Chem. 76, 3029–3036 (2004).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  79. 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 

  80. Wilm, M. & Mann, M. Analytical properties of the nanoelectrospray ion source. Anal. Chem. 68, 1–8 (1996).

    Article  CAS  PubMed  Google Scholar 

  81. 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 

  82. Karas, M., Bachmann, D., Bahr, U. & Hillenkamp, F. Matrix-assisted ultraviolet-laser desorption of nonvolatile compounds. Int. J. Mass Spectrom. Ion Process. 78, 53–68 (1987).

    Article  CAS  Google Scholar 

  83. Clauser, K.R., Baker, P. & Burlingame, A.L. Role of accurate mass measurement (+/− 10 ppm) in protein identification strategies employing MS or MS/MS and database searching. Anal. Chem. 71, 2871–2882 (1999).

    Article  CAS  PubMed  Google Scholar 

  84. Perkins, D.N., Pappin, D.J.C., Creasy, D.M. & Cottrell, J.S. Probability-based protein identification by searching sequence databases using mass spectrometry data. Electrophoresis 20, 3551–3567 (1999).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  86. Elias, J.E. & Gygi, S.P. Target-decoy search strategy for increased confidence in large-scale protein identifications by mass spectrometry. Nat. Methods 4, 207–214 (2007).

    Article  CAS  PubMed  Google Scholar 

  87. Olsen, J.V. & Mann, M. Improved peptide identification in proteomics by two consecutive stages of mass spectrometric fragmentation. Proc. Natl. Acad. Sci. USA 101, 13417–13422 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Nesvizhskii, A.I. & Aebersold, R. Interpretation of shotgun proteomic data—the protein inference problem. Mol. Cell. Proteomics 4, 1419–1440 (2005).

    Article  CAS  PubMed  Google Scholar 

  89. Brazma, A., Krestyaninova, M. & Sarkans, U. Standards for systems biology. Nat. Rev. Genet. 7, 593–605 (2006).

    Article  CAS  PubMed  Google Scholar 

  90. Taylor, C. F. et al. The minimum information about a proteomics experiment (MIAPE). Nat. Biotechnol. 25, 887–893 (2007).

    Article  CAS  PubMed  Google Scholar 

  91. Orchard, S. et al. The minimum information required for reporting a molecular interaction experiment (MIMIx). Nat. Biotechnol. 25, 894–898 (2007).

    Article  CAS  PubMed  Google Scholar 

  92. Gerber, S.A., Rush, J., Stemman, O., Kirschner, M.W. & Gygi, S.P. Absolute quantification of proteins and phosphoproteins from cell lysates by tandem MS. Proc. Natl. Acad. Sci. USA 100, 6940–6945 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Aloy, P. et al. Structure-based assembly of protein complexes in yeast. Science 303, 2026–2029 (2004).

    Article  CAS  PubMed  Google Scholar 

  94. Schirle, M., Heurtier, M.A. & Kuster, B. Profiling core proteomes of human cell lines by one-dimensional PAGE and liquid chromatography-tandem mass spectrometry. Mol. Cell. Proteomics 2, 1297–1305 (2003).

    Article  CAS  PubMed  Google Scholar 

  95. Krogan, N.J. et al. Global landscape of protein complexes in the yeast Saccharomyces cerevisiae. Nature 440, 637–643 (2006).

    Article  CAS  PubMed  Google Scholar 

  96. Gavin, A.C. et al. Proteome survey reveals modularity of the yeast cell machinery. Nature 440, 631–636 (2006).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  98. 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 

  99. Andersen, J.S. & Mann, M. Organellar proteomics: turning inventories into insights. EMBO Rep. 7, 874–879 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Goh, K.I. et al. The human disease network. Proc. Natl. Acad. Sci. USA 104, 8685–8690 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank the members of the Center for Molecular Medicine of the Austrian Academy of Sciences (CeMM) for fruitful discussions, and K. Bennett, J. Colinge and T. Buerckstuemmer for critical reading of the manuscript. Work in our laboratory is supported by the Austrian Academy of Sciences, the Austrian Federal Ministry for Science and Research with the DRAGON and APP-II projects of the GEN-AU program, by the Austrian Science Fund FWF and the Austrian National Bank. We apologize to colleagues if due to space limitations we omitted important original research papers.

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    Thomas Köcher & Giulio Superti-Furga

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Correspondence to Thomas Köcher or Giulio Superti-Furga.

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Köcher, T., Superti-Furga, G. Mass spectrometry–based functional proteomics: from molecular machines to protein networks. Nat Methods 4, 807–815 (2007). https://doi.org/10.1038/nmeth1093

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