Advertisement

Mass Spectrometry-Driven Proteomics: An Introduction

  • Kenny HelsensEmail author
  • Lennart Martens
  • Joël Vandekerckhove
  • Kris Gevaert
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 753)

Abstract

Proteins are reckoned to be the key actors in a living organism. By studying proteins, one engages into deciphering a complex series of events occurring during a protein’s life span. This starts at the creation of a protein, which is tightly controlled on both a transcriptional (Williams and Tyler, 2007, Curr Opin Genet Dev 17, 88–93) and a translational level (Van Der Kelen et al., 2009, Crit Rev Biochem Mol Biol 44, 143–168). During translation, a primary strand of amino acids undergoes a complex folding process in order to obtain a native three-dimensional protein structure (Gross et al., 2003, Cell 115, 739–750). Proteins take on a plethora of functions, such as complex formation, receptor activity, and signal transduction, which ultimately adds up to a cellular phenotype. Consequently, protein analysis is of major interest in molecular biology and involves annotating their presence and localization, as well as their modification state and biochemical context. To accomplish this, many methods have been developed over the last decades, and their general principles and important recent advances in large-scale protein analysis or proteomics are discussed in this review.

Key words

Mass spectrometry peptide-centric proteomics proteomics bioinformatics gel-free proteomics protein modifications 

Notes

Acknowledgment

K.H. is supported by a Ph.D. grant from the Institute for the Promotion of Innovation through Science and Technology in Flanders (IWT-Vlaanderen).

References

  1. 1.
    Williams, S.K. & Tyler, J.K. (2007) Transcriptional regulation by chromatin disassembly and reassembly. Curr Opin Genet Dev 17, 88–93.PubMedCrossRefGoogle Scholar
  2. 2.
    Van Der Kelen, K., Beyaert, R., Inzé, D. & De Veylder, L. (2009) Translational control of eukaryotic gene expression. Crit Rev Biochem Mol Biol 44, 143–168.CrossRefGoogle Scholar
  3. 3.
    Gross, J.D. et al. (2003) Ribosome loading onto the mRNA cap is driven by conformational coupling between eIF4G and eIF4E. Cell 115, 739–750.PubMedCrossRefGoogle Scholar
  4. 4.
    Edman, P. (1950) Method for determination of the amino acid sequence in peptides. Acta Chem Scand 4, 283–293.CrossRefGoogle Scholar
  5. 5.
    Niall, H. (1973) Automated Edman degradation: the protein sequenator. Methods Enzymol 27, 942–1010.PubMedCrossRefGoogle Scholar
  6. 6.
    de Godoy, L.M.F. et al. (2006) Status of complete proteome analysis by mass spectrometry: SILAC labeled yeast as a model system. Genome Biol 7, R50.PubMedCrossRefGoogle Scholar
  7. 7.
    Svensson, H. (1961) Isoelectric fractionation, analysis, and characterization of ampholytes in natural pH gradients. Acta Chem Scand 15, 325.CrossRefGoogle Scholar
  8. 8.
    Laemmli, U.K. (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227, 680–685.PubMedCrossRefGoogle Scholar
  9. 9.
    O‘Farrell, P.H. (1975) High resolution two-dimensional electrophoresis of proteins. J Biol Chem 250, 4007–4021.PubMedGoogle Scholar
  10. 10.
    Klose, J. (1975) Protein mapping by combined isoelectric focusing and electrophoresis of mouse tissues. Hum Genet 26, 231–243.Google Scholar
  11. 11.
    Lauber, W.M. et al. (2001) Mass spectrometry compatibility of two-dimensional gel protein stains. Electrophoresis 22, 906–918.PubMedCrossRefGoogle Scholar
  12. 12.
    Vandekerckhove, J., Bauw, G., Puype, M., Van Damme, J. & Van Montagu, M. (1985) Protein-blotting on Polybrene-coated glass-fiber sheets. A basis for acid hydrolysis and gas-phase sequencing of picomole quantities of protein previously separated on sodium dodecyl sulfate/polyacrylamide gel. Eur J Biochem 152, 9–19.PubMedCrossRefGoogle Scholar
  13. 13.
    Pappin, D.J., Hojrup, P. & Bleasby, A.J. (1993) Rapid identification of proteins by peptide-mass fingerprinting. Curr Biol 3, 327–332.PubMedCrossRefGoogle Scholar
  14. 14.
    Felinger, A. (2008) Molecular dynamic theories in chromatography. J Chromatogr A 1184, 20–41.PubMedCrossRefGoogle Scholar
  15. 15.
    Imoto, T. & Yamada, H. (1983) Peptide separation by reversed-phase high-performance liquid chromatography. Mol Cell Biochem 51, 111–121.PubMedCrossRefGoogle Scholar
  16. 16.
    Tanaka, K., Waki, H., Ido, Y., Akita, S. & Yoshida, Y. (1988) Protein and polymer analyses up to m/z 100,000 by laser ionization time-of-flight mass spectrometry. Rapid Commun Mass Spectrom 2, 151–153.CrossRefGoogle Scholar
  17. 17.
    Karas, M. & Hillenkamp, F. (1988) Laser desorption ionization of proteins with molecular masses exceeding 10,000 daltons. Anal Chem 60, 2299–2301.PubMedCrossRefGoogle Scholar
  18. 18.
    Zenobi, R. & Knochenmuss, R. (1998) Ion formation in MALDI mass spectrometry. Mass Spectrom Rev 17, 337–366.CrossRefGoogle Scholar
  19. 19.
    Fenn, J.B., Mann, M., Meng, C.K., Wong, S.F. & Whitehouse, C.M. (1989) Electrospray ionization for mass spectrometry of large biomolecules. Science 246, 64–71.PubMedCrossRefGoogle Scholar
  20. 20.
    Taylor, G. (1964) Disintegration of water drops in an electric field. Proc R Soc Lond A 280, 383–397.CrossRefGoogle Scholar
  21. 21.
    Rayleigh, L. (1882) Further observations upon liquid jets. Proc R Soc Lond 34, 130–145.CrossRefGoogle Scholar
  22. 22.
    Rietschel, B. et al. (2009) The benefit of combining nLC-MALDI-Orbitrap MS data with nLC-MALDI-TOF/TOF data for proteomic analyses employing elastase. J Proteome Res 8, 5317–5324.PubMedCrossRefGoogle Scholar
  23. 23.
    Paul, W. & Steinwedel, H. (1953) Ein neues Massenspektrometer ohne Magnetfeld. Zeitschrift Naturforschung Teil A 8, 448–448.Google Scholar
  24. 24.
    March, R. (2009) Quadrupole ion traps. Mass Spectrom Rev 28, 961–989.PubMedCrossRefGoogle Scholar
  25. 25.
    Makarov, A. et al. (2006) Performance evaluation of a hybrid linear ion trap/orbitrap mass spectrometer. Anal Chem 78, 2113–2120.PubMedCrossRefGoogle Scholar
  26. 26.
    Makarov, A. (2000) Electrostatic axially harmonic orbital trapping: a high-performance technique of mass analysis. Anal Chem 72, 1156–1162.PubMedCrossRefGoogle Scholar
  27. 27.
    Mclafferty, F.W. (1994) High-resolution tandem FT mass spectrometry above 10 kDa. Acc Chem Res 27, 379–386.CrossRefGoogle Scholar
  28. 28.
    Kameyama, A. (2006) Glycomics using mass spectrometry. Trends Glycosci Glycotechnol 18, 323–341.CrossRefGoogle Scholar
  29. 29.
    Villén, J., Beausoleil, S.A. & Gygi, S.P. (2008) Evaluation of the utility of neutral-loss-dependent MS3 strategies in large-scale phosphorylation analysis. Proteomics 8, 4444.PubMedCrossRefGoogle Scholar
  30. 30.
    Olsen, J. et al. (2009) A dual pressure linear ion trap – Orbitrap instrument with very high sequencing speed. Mol Cell Proteomics 8, 2759–2769.PubMedCrossRefGoogle Scholar
  31. 31.
    Wiza, J. (1979) Microchannel plate detectors. Nucl Instrum Methods 162, 587–601.CrossRefGoogle Scholar
  32. 32.
    Farnsworth, P. (1934) Electron multiplier. US Patent 1,969,399.Google Scholar
  33. 33.
    Roepstorff, P. & Fohlman, J. (1984) Letter to the editors. Biol Mass Spectrom 11, 601.CrossRefGoogle Scholar
  34. 34.
    Wells, J. & McLuckey, S. (2005) Collision-induced dissociation (CID) of peptides and proteins. Methods Enzymol 402, 148–185.PubMedCrossRefGoogle Scholar
  35. 35.
    Falick, A., Hines, W., Medzihradszky, K., Baldwin, M. & Gibson, B. (1993) Low-mass ions produced from peptides by high-energy collision-induced dissociation in tandem mass spectrometry. J Am Soc Mass Spectrom 4, 882–893.CrossRefGoogle Scholar
  36. 36.
    Huang, Y. et al. (2008) A data-mining scheme for identifying peptide structural motifs responsible for different MS/MS fragmentation intensity patterns. J Proteome Res 7, 70–79.PubMedCrossRefGoogle Scholar
  37. 37.
    DeGnore, J. & Qin, J. (1998) Fragmentation of phosphopeptides in an ion trap mass spectrometer. J Am Soc Mass Spectrom 9, 1175–1188.PubMedCrossRefGoogle Scholar
  38. 38.
    Syka, J., Coon, J. & Schroeder, M. (2004) Peptide and protein sequence analysis by electron transfer dissociation mass spectrometry. Proc Natl Acad Sci 101, 9528–9533.PubMedCrossRefGoogle Scholar
  39. 39.
    Zubarev, R., Kelleher, N. & McLafferty, F. (1998) Electron capture dissociation of multiply charged protein cations. A nonergodic process. J Am Chem Soc 120, 3265–3266.CrossRefGoogle Scholar
  40. 40.
    Molina, H., Horn, D.M., Tang, N., Mathivanan, S. & Pandey, A. (2007) Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry. Proc Natl Acad Sci USA 104, 2199–2204.PubMedCrossRefGoogle Scholar
  41. 41.
    Chi, A. et al. (2007) Analysis of phosphorylation sites on proteins from Saccharomyces cerevisiae by electron transfer dissociation (ETD) mass spectrometry. Proc Natl Acad Sci USA 104, 2193–2198.PubMedCrossRefGoogle Scholar
  42. 42.
    Kondrat, R.W., Mcclusky, G.A. & Cooks, R.G. (1978) Multiple reaction monitoring in mass spectrometry/mass spectrometry for direct analysis of complex mixtures. Anal Chem 50, 2017–2021.CrossRefGoogle Scholar
  43. 43.
    Stahl-Zeng, J. et al. (2007) High sensitivity detection of plasma proteins by multiple reaction monitoring of N-glycosites. Mol Cell Proteomics 6, 1809–1817.PubMedCrossRefGoogle Scholar
  44. 44.
    Picotti, P., Bodenmiller, B., Mueller, L.N., Domon, B. & Aebersold, R. (2009) Full dynamic range proteome analysis of S. cerevisiae by targeted proteomics. Cell 138, 795–806.PubMedCrossRefGoogle Scholar
  45. 45.
    Lange, V., Picotti, P., Domon, B. & Aebersold, R. (2008) Selected reaction monitoring for quantitative proteomics: a tutorial. Mol Syst Biol 4, 222.PubMedCrossRefGoogle Scholar
  46. 46.
    Liu, H., Sadygov, R.G. & Yates, J.R. (2004) A model for random sampling and estimation of relative protein abundance in shotgun proteomics. Anal Chem 76, 4193–4201.PubMedCrossRefGoogle Scholar
  47. 47.
    Washburn, M., Wolters, D. & Yates, J. (2001) Large-scale analysis of the yeast proteome by multidimensional protein identification technology. Nat Biotechnol 19, 242–247.PubMedCrossRefGoogle Scholar
  48. 48.
    Link, A. et al. (1999) Direct analysis of protein complexes using mass spectrometry. Nat Biotechnol 17, 676–682.PubMedCrossRefGoogle Scholar
  49. 49.
    Peng, J., Elias, J., Thoreen, C., Licklider, L. & Gygi, S. (2003) Evaluation of multidimensional chromatography coupled with tandem mass spectrometry (LC/LC-MS/MS) for large-scale protein analysis: the yeast proteome. J Proteome Res 2, 43–50.PubMedCrossRefGoogle Scholar
  50. 50.
    Dix, M.M., Simon, G.M. & Cravatt, B.F. (2008) Global mapping of the topography and magnitude of proteolytic events in apoptosis. Cell 134, 679–691.PubMedCrossRefGoogle Scholar
  51. 51.
    de Godoy, L.M.F. et al. (2008) Comprehensive mass-spectrometry-based proteome quantification of haploid versus diploid yeast. Nature 455, 1251–1254.PubMedCrossRefGoogle Scholar
  52. 52.
    Ghaemmaghami, S. et al. (2003) Global analysis of protein expression in yeast. Nature 425, 737–741.PubMedCrossRefGoogle Scholar
  53. 53.
    Huh, W.-K. et al. (2003) Global analysis of protein localization in budding yeast. Nature 425, 686–691.PubMedCrossRefGoogle Scholar
  54. 54.
    Nesvizhskii, A.I. & Aebersold, R. (2005) Interpretation of shotgun proteomic data: the protein inference problem. Mol Cell Proteomics 4, 1419–1440.PubMedCrossRefGoogle Scholar
  55. 55.
    Gygi, S.P. et al. (1999) Quantitative analysis of complex protein mixtures using isotope-coded affinity tags. Nat Biotechnol 17, 994–999.PubMedCrossRefGoogle Scholar
  56. 56.
    Gevaert, K. et al. (2002) Chromatographic isolation of methionine-containing peptides for gel-free proteome analysis: identification of more than 800 Escherichia coli proteins. Mol Cell Proteomics 1, 896–903.PubMedCrossRefGoogle Scholar
  57. 57.
    Gevaert, K. et al. (2007) A la carte proteomics with an emphasis on gel-free techniques. Proteomics 7, 2698–2718.PubMedCrossRefGoogle Scholar
  58. 58.
    Gevaert, K. et al. (2003) Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides. Nat Biotechnol 21, 566–569.PubMedCrossRefGoogle Scholar
  59. 59.
    Staes, A. et al. (2008) Improved recovery of proteome-informative, protein N-terminal peptides by combined fractional diagonal chromatography (COFRADIC). Proteomics 8, 1362–1370.PubMedCrossRefGoogle Scholar
  60. 60.
    Jensen, O. (2006) Interpreting the protein language using proteomics. Nat Rev Mol Cell Biol 7, 391–403.PubMedCrossRefGoogle Scholar
  61. 61.
    Enoksson, M. et al. (2007) Identification of proteolytic cleavage sites by quantitative proteomics. J Proteome Res 6, 2850–2858.PubMedCrossRefGoogle Scholar
  62. 62.
    Timmer, J.C. et al. (2007) Profiling constitutive proteolytic events in vivo. Biochem J 407, 41–48.PubMedCrossRefGoogle Scholar
  63. 63.
    Doucet, A. & Overall, C.M. (2008) Protease proteomics: revealing protease in vivo functions using systems biology approaches. Mol Aspects Med 29, 339–358.PubMedCrossRefGoogle Scholar
  64. 64.
    Mahrus, S. et al. (2008) Global sequencing of proteolytic cleavage sites in apoptosis by specific labeling of protein N termini. Cell 134, 866–876.PubMedCrossRefGoogle Scholar
  65. 65.
    Andersson, L. & Porath, J. (1986) Isolation of phosphoproteins by immobilized metal (Fe-3+) affinity chromatography. Anal Biochem 154, 250–254.PubMedCrossRefGoogle Scholar
  66. 66.
    Bonenfant, D. et al. (2003) Quantitation of changes in protein phosphorylation: a simple method based on stable isotope labeling and mass spectrometry. Proc Natl Acad Sci USA 100, 880–885.PubMedCrossRefGoogle Scholar
  67. 67.
    Pinkse, M., Uitto, P., Hilhorst, M., Ooms, B. & Heck, A. (2004) Selective isolation at the femtomole level of phosphopeptides from proteolytic digests using 2D-nanoLC-ESI-MS/MS and titanium oxide precolumns. Anal Chem 76, 3935–3943.PubMedCrossRefGoogle Scholar
  68. 68.
    Mcnulty, D. & Annan, R. (2008) Hydrophilic interaction chromatography reduces the complexity of the phosphoproteome and improves global phosphopeptide isolation and detection. Mol Cell Proteomics 7, 971.PubMedCrossRefGoogle Scholar
  69. 69.
    Beausoleil, S. et al. (2004) Large-scale characterization of HeLa cell nuclear phosphoproteins. Proc Natl Acad Sci USA 101, 12130–12135.PubMedCrossRefGoogle Scholar
  70. 70.
    Geng, M., Zhang, X., Bina, M. & Regnier, F. (2001) Proteomics of glycoproteins based on affinity selection of glycopeptides from tryptic digests. J Chromatogr B 752, 293–306.CrossRefGoogle Scholar
  71. 71.
    Zhang, H., Yan, W. & Aebersold, R. (2004) Chemical probes and tandem mass spectrometry: a strategy for the quantitative analysis of proteomes and subproteomes. Curr Opin Chem Biol 8, 66–75.PubMedCrossRefGoogle Scholar
  72. 72.
    Khidekel, N. et al. (2007) Probing the dynamics of O-GlcNAc glycosylation in the brain using quantitative proteomics. Nat Chem Biol 3, 339–348.PubMedCrossRefGoogle Scholar
  73. 73.
    Choudhary, C. et al. (2009) Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science 325, 834–840.PubMedCrossRefGoogle Scholar
  74. 74.
    Peng, J. et al. (2003) A proteomics approach to understanding protein ubiquitination. Nat Biotechnol 21, 921–926.PubMedCrossRefGoogle Scholar
  75. 75.
    Aebersold, R. & Mann, M. (2003) Mass spectrometry-based proteomics. Nature 422, 198–207.PubMedCrossRefGoogle Scholar
  76. 76.
    Lahm, H. & Langen, H. (2000) Mass spectrometry: a tool for the identification of proteins separated by gels. Electrophoresis 21, 2105–2114.PubMedCrossRefGoogle Scholar
  77. 77.
    Ong, S. et al. (2002) Stable isotope labeling by amino acids in cell culture, SILAC, as a simple and accurate approach to expression proteomics. Mol Cell Proteomics 1, 376–386.PubMedCrossRefGoogle Scholar
  78. 78.
    Mann, M. (2006) Functional and quantitative proteomics using SILAC. Nat Rev Mol Cell Biol 7, 952–958.PubMedCrossRefGoogle Scholar
  79. 79.
    Krueger, M. et al. (2008) SILAC mouse for quantitative proteomics uncovers kindlin-3 as an essential factor for red blood cell function. Cell 134, 353–364.CrossRefGoogle Scholar
  80. 80.
    Krijgsveld, J. et al. (2003) Metabolic labeling of C. elegans and D. melanogaster for quantitative proteomics. Nat Biotechnol 21, 927–931.PubMedCrossRefGoogle Scholar
  81. 81.
    Han, D.K., Eng, J., Zhou, H. & Aebersold, R. (2001) Quantitative profiling of differentiation-induced microsomal proteins using isotope-coded affinity tags and mass spectrometry. Nat Biotechnol 19, 946–951.PubMedCrossRefGoogle Scholar
  82. 82.
    Staes, A. et al. (2004) Global differential non-gel proteomics by quantitative and stable labeling of tryptic peptides with oxygen-18. J Proteome Res 3, 786–791.PubMedCrossRefGoogle Scholar
  83. 83.
    Ross, P. et al. (2004) Multiplexed protein quantitation in Saccharomyces cerevisiae using amine-reactive isobaric tagging reagents. Mol Cell Proteomics 3, 1154–1169.PubMedCrossRefGoogle Scholar
  84. 84.
    Gerber, S., Rush, J., Stemman, O., Kirschner, M. & Gygi, S. (2003) Absolute quantification of proteins and phosphoproteins from cell lysates by tandem MS. Proc Natl Acad Sci USA 100, 6940–6945.PubMedCrossRefGoogle Scholar
  85. 85.
    Malmström, J. et al. (2009) Proteome-wide cellular protein concentrations of the human pathogen Leptospira interrogans. Nature 460, 762–765.PubMedCrossRefGoogle Scholar
  86. 86.
    Choi, H., Fermin, D. & Nesvizhskii, A. (2008) Significance analysis of spectral count data in label-free shotgun proteomics. Mol Cell Proteomics 7, 2373.PubMedCrossRefGoogle Scholar
  87. 87.
    Wiener, M., Sachs, J., Deyanova, E. & Yates, N. (2004) Differential mass spectrometry: a label-free LC-MS method for finding significant differences in complex peptide and protein mixtures. Anal Chem 76, 6085–6096.PubMedCrossRefGoogle Scholar
  88. 88.
    Sturm, M. et al. (2008) OpenMS-An open-source software framework for mass spectrometry. BMC Bioinformatics 9, 163.PubMedCrossRefGoogle Scholar
  89. 89.
    Cox, J. & Mann, M. (2008) MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification. Nat Biotechnol 26, 1367–1372.PubMedCrossRefGoogle Scholar
  90. 90.
    Katajamaa, M. & Oresic, M. (2007) Data processing for mass spectrometry-based metabolomics. J Chromatogr A 1158, 318–328.PubMedCrossRefGoogle Scholar
  91. 91.
    Mann, M. & Wilm, M. (1994) Error-tolerant identification of peptides in sequence databases by peptide sequence tags. Anal Chem 66, 4390–4399.PubMedCrossRefGoogle Scholar
  92. 92.
    Reisinger, F. & Martens, L. (2009) Database on Demand – An online tool for the custom generation of FASTA-formatted sequence databases. Proteomics 9, 4421–4424.PubMedCrossRefGoogle Scholar
  93. 93.
    Nesvizhskii, A.I., Vitek, O. & Aebersold, R. (2007) Analysis and validation of proteomic data generated by tandem mass spectrometry. Nat Methods 4, 787–797.PubMedCrossRefGoogle Scholar
  94. 94.
    Yates, J.R., Eng, J.K., McCormack, A.L. & Schieltz, D. (1995) Method to correlate tandem mass spectra of modified peptides to amino acid sequences in the protein database. Anal Chem 67, 1426–1436.PubMedCrossRefGoogle Scholar
  95. 95.
    Perkins, D., Pappin, D., Creasy, D. & Cottrell, J. (1999) Probability-based protein identification by searching sequence databases using mass spectrometry data. Electrophoresis 20, 3551–3567.PubMedCrossRefGoogle Scholar
  96. 96.
    Fenyo, D. & Beavis, R. (2003) A method for assessing the statistical significance of mass spectrometry-based protein identifications using general scoring schemes. Anal Chem 75, 768–774.PubMedCrossRefGoogle Scholar
  97. 97.
    Colinge, J., Masselot, A., Giron, M., Dessingy, T. & Magnin, J. (2003) OLAV: towards high-throughput tandem mass spectrometry data identification. Proteomics 3, 1454–1463.PubMedCrossRefGoogle Scholar
  98. 98.
    Geer, L. et al. (2004) Open mass spectrometry search algorithm. J Proteome Res 3, 958–964.PubMedCrossRefGoogle Scholar
  99. 99.
    Frank, A. & Pevzner, P. (2005) PepNovo: de novo peptide sequencing via probabilistic network modeling. Anal Chem 77, 964–973.PubMedCrossRefGoogle Scholar
  100. 100.
    Johnson, R. & Taylor, J. (2002) Searching sequence databases via de novo peptide sequencing by tandem mass spectrometry. Mol Biotechnol 22, 301–315.PubMedCrossRefGoogle Scholar
  101. 101.
    Elias, J.E. & Gygi, S.P. (2007) Target-decoy search strategy for increased confidence in large-scale protein identifications by mass spectrometry. Nat Methods 4, 207–214.PubMedCrossRefGoogle Scholar
  102. 102.
    Nesvizhskii, A. et al. (2006) Dynamic spectrum quality assessment and iterative computational analysis of shotgun proteomic data – Toward more efficient identification of post-translational modifications, sequence polymorphisms, and novel peptides. Mol Cell Proteomics 5, 652–670.PubMedGoogle Scholar
  103. 103.
    Flikka, K., Martens, L., Vandekerckhoe, J., Gevaert, K. & Eidhammer, I. (2006) Improving the reliability and throughput of mass spectrometry-based proteomics by spectrum quality filtering. Proteomics 6, 2086–2094.PubMedCrossRefGoogle Scholar
  104. 104.
    Keller, A., Nesvizhskii, A., Kolker, E. & Aebersold, R. (2002) Empirical statistical model to estimate the accuracy of peptide identifications made by MS/MS and database search. Anal Chem 74, 5383–5392.PubMedCrossRefGoogle Scholar
  105. 105.
    Kall, L., Canterbury, J.D., Weston, J., Noble, W.S. & MacCoss, M.J. (2007) Semi-supervised learning for peptide identification from shotgun proteomics datasets. Nat Methods 4, 923–925.PubMedCrossRefGoogle Scholar
  106. 106.
    Wan, Y., Yang, A. & Chen, T. (2006) PepHMM: a hidden Markov model based scoring function for mass spectrometry database search. Anal Chem 78, 432–437.PubMedCrossRefGoogle Scholar
  107. 107.
    Helsens, K., Timmerman, E., Vandekerckhove, J., Gevaert, K. & Martens, L. (2008) Peptizer: a tool for assessing false positive peptide identifications and manually validating selected results. Mol Cell Proteomics 7, 2363–2372.Google Scholar
  108. 108.
    Martens, L. & Hermjakob, H. (2007) Proteomics data validation: why all must provide data. Mol Biosyst 3, 518–522.PubMedCrossRefGoogle Scholar
  109. 109.
    Nesvizhskii, A., Keller, A., Kolker, E. & Aebersold, R. (2003) A statistical model for identifying proteins by tandem mass spectrometry. Anal Chem 75, 4646–4658.PubMedCrossRefGoogle Scholar
  110. 110.
    Mueller, M., Martens, L. & Apweiler, R. (2007) Annotating the human proteome: beyond establishing a parts list. Biochim Biophys Acta 1774, 175–191.PubMedGoogle Scholar
  111. 111.
    Shannon, P. et al. (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13, 2498–2504.PubMedCrossRefGoogle Scholar
  112. 112.
    Maere, S., Heymans, K. & Kuiper, M. (2005) BiNGO: a Cytoscape plugin to assess overrepresentation of gene ontology categories in biological networks. Bioinformatics 21, 3448–3449.PubMedCrossRefGoogle Scholar
  113. 113.
    Dennis, G. et al. (2003) DAVID: database for annotation, visualization, and integrated discovery. Genome Biol 4, R60.CrossRefGoogle Scholar
  114. 114.
    Kaplan, N., Vaaknin, A. & Linial, M. (2003) PANDORA: keyword-based analysis of protein sets by integration of annotation sources. Nucleic Acids Res 31, 5617–5626.PubMedCrossRefGoogle Scholar
  115. 115.
    Schneider, T.D. & Stephens, R.M. (1990) Sequence logos: a new way to display consensus sequences. Nucleic Acids Res 18, 6097–6100.PubMedCrossRefGoogle Scholar
  116. 116.
    Colaert, N., Helsens, K., Martens, L., Vandekerckhove, J. & Gevaert, K. (2009) Improved visualization of protein consensus sequences by iceLogo. Nat Methods 6, 786–787.PubMedCrossRefGoogle Scholar
  117. 117.
    Matthiesen, R., Trelle, M., Hojrup, P., Bunkenborg, J. & Jensen, O. (2005) VEMS 3.0: algorithms and computational tools for tandem mass spectrometry based identification of post-translational modifications in proteins. J Proteome Res 4, 2338–2347.PubMedCrossRefGoogle Scholar
  118. 118.
    Rauch, A. et al. (2006) Computational Proteomics Analysis System (CPAS): an extensible, open-source analytic system for evaluating and publishing proteomic data and high throughput biological experiments. J Proteome Res 5, 112–121.PubMedCrossRefGoogle Scholar
  119. 119.
    Hakkinen, J., Vincic, G., Mansson, O., Warell, K. & Levander, F. (2009) The proteios software environment: an extensible multiuser platform for management and analysis of proteomics data. J Proteome Res 8, 3037–3043.PubMedCrossRefGoogle Scholar
  120. 120.
    Hartler, J. et al. (2007) MASPECTRAS: a platform for management and analysis of proteomics LC-MS/MS data. BMC Bioinformatics 8, 197.PubMedCrossRefGoogle Scholar
  121. 121.
    Helsens, K. et al. (2010) ms_lims, a simple yet powerful open source LIMS for mass spectrometry-driven proteomics. Proteomics 10, 2560.CrossRefGoogle Scholar
  122. 122.
    Martens, L. et al. (2005) PRIDE: the proteomics identifications database. Proteomics 5, 3537–3545.PubMedCrossRefGoogle Scholar
  123. 123.
    Slotta, D.J., Barrett, T. & Edgar, R. (2009) NCBI Peptidome: a new public repository for mass spectrometry peptide identifications. Nat Biotechnol 27, 600–601.PubMedCrossRefGoogle Scholar
  124. 124.
    Desiere, F. et al. (2006) The PeptideAtlas project. Nucleic Acids Res 34, D655–D658.PubMedCrossRefGoogle Scholar
  125. 125.
    Craig, R., Cortens, J.P. & Beavis, R.C. (2004) Open source system for analyzing, validating, and storing protein identification data. J Proteome Res 3, 1234–1242.PubMedCrossRefGoogle Scholar
  126. 126.
    Klie, S. et al. (2008) Analyzing large-scale proteomics projects with latent semantic indexing. J Proteome Res 7, 182–191.PubMedCrossRefGoogle Scholar
  127. 127.
    Mueller, M. et al. (2008) Analysis of the experimental detection of central nervous system-related genes in human brain and cerebrospinal fluid datasets. Proteomics 8, 1138–1148.PubMedCrossRefGoogle Scholar
  128. 128.
    Gevaert K, Ghesquière B, et al (2004) Reversible labeling of cysteine-containing peptides allows their specific chromatographic isolation for non-gel proteome studies. Proteomics 4, 897–908.PubMedCrossRefGoogle Scholar
  129. 129.
    Gevaert K, Staes A, et al (2005) Global phosphoproteome analysis on human HepG2 hepatocytes using reversed-phase diagonal LC. Proteomics 5, 3589–3599.PubMedCrossRefGoogle Scholar
  130. 130.
    Ghesquière B, Van Damme J, et al (2006) Proteome-wide characterization of N-glycosylation events by diagonal chromatography. J Proteome Res 5, 2438–2447.PubMedCrossRefGoogle Scholar
  131. 131.
    Hanoulle X, Van Damme J, et al (2006) A new functional, chemical proteomics technology to identify purine nucleotide binding sites in complex proteomes. J Proteome Res 5, 3438–3445.PubMedCrossRefGoogle Scholar
  132. 132.
    Ghesquière B, Buyl L, et al (2007) A new approach for mapping sialylated N-glycosites in serum proteomes. J Proteome Res 6, 4304–4312.PubMedCrossRefGoogle Scholar
  133. 133.
    Ghesquière B, Colaert N, et al (2009) In vitro and in vivo protein-bound tyrosine nitration characterized by diagonal chromatography. Mol Cell Proteomics 8, 2642–2652.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Kenny Helsens
    • 1
    • 2
    Email author
  • Lennart Martens
    • 1
    • 2
  • Joël Vandekerckhove
    • 3
  • Kris Gevaert
    • 3
  1. 1.Department of Medical Protein ResearchVIB, Ghent UniversityGhentBelgium
  2. 2.Department of BiochemistryGhent UniversityGhentBelgium
  3. 3.VIB Department of Medical Protein Research and UGent Department of BiochemistryVIB and Ghent UniversityGhentBelgium

Personalised recommendations