Proteomics in the Systems-Level Study of the Metabolic Syndrome

  • Isabel Rubio-Aliaga
  • Irma Silva-Zolezzi
  • Michael Affolter
  • Loïc Dayon
  • Alexandre Panchaud
  • Martin KussmannEmail author


Proteomics has come a long way from the initial qualitative analysis of proteins present in a given sample to the large-scale characterization of proteomes, their interactions and dynamic behaviour in time and space. Originally enabled by breakthroughs in protein separation and visualization (by two-dimensional gels electrophoresis) and protein identification (by mass spectrometry), the discipline now encompasses a large body of protein and peptide separation, labelling, detection and sequencing tools supported by stable-isotope- and label-free techniques and computational data processing for quantitative proteomics. The key functional importance to investigate the protein complement has driven the study of proteomes in numerous physiological and pathological conditions. Proteomics has been mainly applied in discovering novel biomarkers of disease, evidenced by the fact that most clinical tests today measure proteins in blood. Moreover, understanding the proteome helps investigate health and disease states and understand the mechanisms of action of specific molecules, e.g., nutrients or drugs. Here, we briefly recapitulate proteomic technologies and cover their evolution to today’s and future cutting-edge platforms. Then we review and discuss proteomic applications to the study of the metabolic syndrome.


Proteomics Diabetes Obesity Metabolic syndrome Mass spectrometry Systems biology 


  1. Adachi J, Kumar C, Zhang Y, Mann M (2007) In-depth analysis of the adipocyte proteome by mass spectrometry and bioinformatics. Mol Cell Proteomics 6(7):1257–12739PubMedCrossRefGoogle Scholar
  2. Aebersold R, Mann M (2003) Mass spectrometry-based proteomics. Nature 422(6928):198–207PubMedCrossRefGoogle Scholar
  3. Ahmed M, Neville MJ, Edelmann MJ, Kessler BM, Karpe F (2010) Proteomic analysis of human adipose tissue after rosiglitazone treatment shows coordinated changes to promote glucose uptake. Obesity 18(1):27–34PubMedCrossRefGoogle Scholar
  4. Ahrens CH, Brunner E, Qeli E, Basler K, Aebersold R (2010) Generating and navigating proteome maps using mass spectrometry. Nat Rev Mol Cell Bio 11(11):789–801CrossRefGoogle Scholar
  5. Alaiya A, Al-Mohanna M, Linder S (2005) Clinical cancer proteomics: promises and pitfalls. J Proteome Res 4(4):1213–1222PubMedCrossRefGoogle Scholar
  6. Alkhalaf A, Zurbig P, Bakker SJ, Bilo HJ, Cerna M, Fischer C, Fuchs S, Janssen B, Medek K, Mischak H, Roob JM, Rossing K, Rossing P, Rychlik I, Sourij H, Tiran B, Winklhofer-Roob BM, Navis GJ, Group PREDICTIONS (2010) Multicentric validation of proteomic biomarkers in urine specific for diabetic nephropathy. PLoS ONE (Electronic Resource) 5(10):e13421PubMedCrossRefGoogle Scholar
  7. Allet N, Barrillat N, Baussant T, Boiteau C, Botti P, Bougueleret L, Budin N, Canet D, Carraud S, Chiappe D, Christmann N, Colinge J, Cusin I, Dafflon N, Depresle B, Fasso I, Frauchiger P, Gaertner H, Gleizes A, Gonzalez-Couto E, Jeandenans C, Karmime A, Kowall T, Lagache S, Mahe E, Masselot A, Mattou H, Moniatte M, Niknejad A, Paolini M, Perret F, Pinaud N, Ranno F, Raimondi S, Reffas S, Regamey PO, Rey PA, Rodriguez-Tome P, Rose K, Rossellat G, Saudrais C, Schmidt C, Villain M, Zwahlen C (2004) In vitro and in silico processes to identify differentially expressed proteins. Proteomics 4(8):2333–2351PubMedCrossRefGoogle Scholar
  8. Amacher DE (1998) Serum transaminase elevations as indicators of hepatic injury following the administration of drugs. Regul Toxicol Pharmacol 27(2):119–130PubMedCrossRefGoogle Scholar
  9. Arvidsson E, Viguerie N, Andersson I, Verdich C, Langin D, Arner P (2004) Effects of different hypocaloric diets on protein secretion from adipose tissue of obese women. Diabetes 53(8):1966–1971PubMedCrossRefGoogle Scholar
  10. Banks RE, Dunn MJ, Hochstrasser DF, Sanchez JC, Blackstock W, Pappin DJ, Selby PJ (2000) Proteomics: new perspectives, new biomedical opportunities. Lancet 356(9243):1749–1756PubMedCrossRefGoogle Scholar
  11. Bateman RH, Carruthers R, Hoyes JB, Jones C, Langridge JI, Millar A, Vissers JP (2002) A novel precursor ion discovery method on a hybrid quadrupole orthogonal acceleration time-of-flight (Q-TOF) mass spectrometer for studying protein phosphorylation. J Am Soc Mass Spectrom 13(7):792–803PubMedCrossRefGoogle Scholar
  12. Bendall SC, Simonds EF, Qiu P, Amir el-AD, Krutzik PO, Finck R, Bruggner RV, Melamed R, Trejo A, Ornatsky OI, Balderas RS, Plevritis SK, Sachs K, Pe’er D, Tanner SD, Nolan GP (2011) Single-cell mass cytometry of differential immune and drug responses across a human hematopoietic continuum. Science 332(6030):687–696PubMedCrossRefGoogle Scholar
  13. Beynon RJ, Doherty MK, Pratt JM, Gaskell SJ (2005) Multiplexed absolute quantification in proteomics using artificial QCAT proteins of concatenated signature peptides. Nat Methods 2(8):587–589PubMedCrossRefGoogle Scholar
  14. Birner-Gruenberger R, Susani-Etzerodt H, Waldhuber M, Riesenhuber G, Schmidinger H, Rechberger G, Kollroser M, Strauss JG, Lass A, Zimmermann R, Haemmerle G, Zechner R, Hermetter A (2005) The lipolytic proteome of mouse adipose tissue. Mol Cell Proteomics 4(11):1710–1717PubMedCrossRefGoogle Scholar
  15. Bouwman FG, Claessens M, Baak MA van, Noben JP, Wang P, Saris WH, Mariman EC (2009) The physiologic effects of caloric restriction are reflected in the in vivo adipocyte-enriched proteome of overweight/obese subjects. J Proteome Res 8(12):5532–5540PubMedCrossRefGoogle Scholar
  16. Brody EN, Gold L, Lawn RM, Walker JJ, Zichi D (2010) High-content affinity-based proteomics: unlocking protein biomarker discovery. Expert Rev Mol Diagn 10(8):1013–1022PubMedCrossRefGoogle Scholar
  17. Brunner Y, Coute Y, Iezzi M, Foti M, Fukuda M, Hochstrasser DF, Wollheim CB, Sanchez JC (2007) Proteomics analysis of insulin secretory granules. Mol Cell Proteomics 6(6):1007–1017PubMedCrossRefGoogle Scholar
  18. Calvo SE, Mootha VK (2010) The mitochondrial proteome and human disease. Annu Rev Genomics Hum Genet 11:25–44PubMedCrossRefGoogle Scholar
  19. Cargile BJ, Stephenson JL Jr (2004) An alternative to tandem mass spectrometry: isoelectric point and accurate mass for the identification of peptides. Anal Chem 76(2):267–275PubMedCrossRefGoogle Scholar
  20. Chelius D, Bondarenko PV (2002) Quantitative profiling of proteins in complex mixtures using liquid chromatography and mass spectrometry. J Proteome Res 1(4):317–323PubMedCrossRefGoogle Scholar
  21. Colinge J, Masselot A, Giron M, Dessingy T, Magnin J (2003) OLAV: towards high-throughput tandem mass spectrometry data identification. Proteomics 3(8):1454–1463PubMedCrossRefGoogle Scholar
  22. Collins H, Najafi H, Buettger C, Rombeau J, Settle RG, Matschinsky FM (1992) Identification of glucose response proteins in two biological models of beta-cell adaptation to chronic high glucose exposure. J Biol Chem 267(2):1357–1366PubMedGoogle Scholar
  23. Conrads TP, Anderson GA, Veenstra TD, Pasa Tolic L, Smith RD (2000) Utility of accurate mass tags for proteome-wide protein identification. Anal Chem 72:3349–3354 (15 Jul 2000)PubMedCrossRefGoogle Scholar
  24. Corton M, Villuendas G, Botella JI, San Millan JL, Escobar-Morreale HF, Peral B (2004) Improved resolution of the human adipose tissue proteome at alkaline and wide range pH by the addition of hydroxyethyl disulfide. Proteomics 4(2):438–441PubMedCrossRefGoogle Scholar
  25. Craig R, Beavis RC (2004) TANDEM: matching proteins with tandem mass spectra. Bioinformatics 20(9):1466–1467PubMedCrossRefGoogle Scholar
  26. Cyranoski D (2010) China pushes for the proteome. Nature 467:380PubMedCrossRefGoogle Scholar
  27. Deng Y, Scherer PE (2010) Adipokines as novel biomarkers and regulators of the metabolic syndrome. Ann N Y Acad Sci 1212:E1–E199PubMedCrossRefGoogle Scholar
  28. Deng WJ, Nie S, Dai J, Wu JR, Zeng R (2010) Proteome, phosphoproteome, and hydroxyproteome of liver mitochondria in diabetic rats at early pathogenic stages. Mol Cell Proteomics 9(1):100–116PubMedCrossRefGoogle Scholar
  29. Domon B, Broder S (2004) Implications of new proteomics strategies for biology and medicine. J Proteome Res 3(2):253–260PubMedCrossRefGoogle Scholar
  30. Edvardsson U, Alexandersson M, Brockenhuus LH von, Nystrom AC, Ljung B, Nilsson F, Dahllof B (1999) A proteome analysis of livers from obese (ob/ob) mice treated with the peroxisome proliferator WY14,643. Electrophoresis 20(4–5):935–942PubMedCrossRefGoogle Scholar
  31. Elias JE, Gygi SP (2007) Target-decoy search strategy for increased confidence in large-scale protein identifications by mass spectrometry. Nat Methods 4(3):207–214PubMedCrossRefGoogle Scholar
  32. Elias JE, Haas W, Faherty BK, Gygi SP (2005) Comparative evaluation of mass spectrometry platforms used in large-scale proteomics investigations. Nat Methods 2(9):667–675PubMedCrossRefGoogle Scholar
  33. Eng JK, McCormack AL, Yates JR (1994) An approach to correlate tandem mass spectral data of peptides with amino acid sequences in a protein database. J Am Soc Mass Spectrom 5:976–989CrossRefGoogle Scholar
  34. Foster LJ, De Hoog CL, Mann M (2003) Unbiased quantitative proteomics of lipid rafts reveals high specificity for signaling factors. Proc Natl Acad Sci U. S. A. 100(10):5813–5818PubMedCrossRefGoogle Scholar
  35. Fu S, Yang L, Li P, Hofmann O, Dicker L, Hide W, Lin X, Watkins SM, Ivanov AR, Hotamisligil GS (2011) Aberrant lipid metabolism disrupts calcium homeostasis causing liver endoplasmic reticulum stress in obesity. Nature 473(7348):528–531PubMedCrossRefGoogle Scholar
  36. Gartner CA, Elias JE, Bakalarski CE, Gygi SP (2007) Catch-and-release reagents for broadscale quantitative proteomics analyses. J Proteome Res 6(4):1482–1491PubMedCrossRefGoogle Scholar
  37. Geer LY, Markey SP, Kowalak JA, Wagner L, Xu M, Maynard DM, Yang X, Shi W, Bryant SH (2004) Open mass spectrometry search algorithm. J Proteome Res 3(5):958–964PubMedCrossRefGoogle Scholar
  38. Gerber SA, Rush J, Stemman O, Kirschner MW, Gygi SP (2003) Absolute quantification of proteins and phosphoproteins from cell lysates by tandem MS. Proc Natl Acad Sci U. S. A. 100(12):6940–6945Google Scholar
  39. Geromanos SJ, Vissers JP, Silva JC, Dorschel CA, Li GZ, Gorenstein MV, Bateman RH, Langridge JI (2009) The detection, correlation, and comparison of peptide precursor and product ions from data independent LC-MS with data dependant LC-MS/MS. Proteomics 9(6):1683–1695PubMedCrossRefGoogle Scholar
  40. Gillet LC, Navarro P, Tate S, Röst H, Selevsek N, Reiter L, Bonner R, Aebersold R (2012) Targeted data extraction of the MS/MS spectra generated by data independent acquisition: a new concept for consistent and accurate proteome analysis. Mol Cell Proteomics 11(6) doi: 10.1074/mcp.O111.016717:1–17Google Scholar
  41. Gold L, Ayers D, Bertino J, Bock C, Bock A, Brody EN, Carter J, Dalby AB, Eaton BE, Fitzwater T, Flather D, Forbes A, Foreman T, Fowler C, Gawande B, Goss M, Gunn M, Gupta S, Halladay D, Heil J, Heilig J, Hicke B, Husar G, Janjic N, Jarvis T, Jennings S, Katilius E, Keeney TR, Kim N, Koch TH, Kraemer S, Kroiss L, Le N, Levine D, Lindsey W, Lollo B, Mayfield W, Mehan M, Mehler R, Nelson SK, Nelson M, Nieuwlandt D, Nikrad M, Ochsner U, Ostroff RM, Otis M, Parker T, Pietrasiewicz S, Resnicow DI, Rohloff J, Sanders G, Sattin S, Schneider D, Singer B, Stanton M, Sterkel A, Stewart A, Stratford S, Vaught JD, Vrkljan M, Walker JJ, Watrobka M, Waugh S, Weiss A, Wilcox SK, Wolfson A, Wolk SK, Zhang C, Zichi D (2010) Aptamer-based multiplexed proteomic technology for biomarker discovery. PLoS.One 5(12):e15004PubMedCrossRefGoogle Scholar
  42. Goodlett DR, Keller A, Watts JD, Newitt R, Yi EC, Purvine S, Eng JK, Haller P von, Aebersold R, Kolker E (2001) Differential stable isotope labeling of peptides for quantitation and de novo sequence derivation. Rapid Commun Mass Spectrom 15(14):1214–1221PubMedCrossRefGoogle Scholar
  43. Gygi S, Rist B, Gerber S, Turecek F, Gelb M, Aebersold R (1999a) Quantitative analysis of complex protein mixtures using isotope-coded affinity tags. Nat Biotechnol 17:994–999CrossRefGoogle Scholar
  44. Gygi SP, Rochon Y, Franza BR, Aebersold R (1999b) Correlation between protein and mRNA abundance in yeast. Mol Cell Biol 19(3):1720–1730Google Scholar
  45. Halaas JL, Gajiwala KS, Maffei M, Cohen SL, Chait BT, Rabinowitz D, Lallone RL, Burley SK, Friedman JM (1995) Weight-reducing effects of the plasma protein encoded by the obese gene. Science 269(5223):543–546PubMedCrossRefGoogle Scholar
  46. Hanke S, Mann M (2009) The phosphotyrosine interactome of the insulin receptor family and its substrates IRS-1 and IRS-2. Mol Cell Proteomics 8(3):519–534PubMedCrossRefGoogle Scholar
  47. Hansen BT, Jones JA, Mason DE, Liebler DC (2001) SALSA: a pattern recognition algorithm to detect electrophile-adducted peptides by automated evaluation of CID spectra in LC-MS-MS analyses. Anal Chem 73(8):1676–1683PubMedCrossRefGoogle Scholar
  48. Hojlund K, Wrzesinski K, Larsen PM, Fey SJ, Roepstorff P, Handberg A, Dela F, Vinten J, McCormack JG, Reynet C, Beck-Nielsen H (2003) Proteome analysis reveals phosphorylation of ATP synthase beta -subunit in human skeletal muscle and proteins with potential roles in type 2 diabetes. J Biol Chem 278(12):10436–10442PubMedCrossRefGoogle Scholar
  49. Hoofnagle AN, Aebersold R, Anderson NL, Felsenfeld A, Liebler DC (2011) Painting a moving picture: large-scale proteomics efforts and their potential for changing patient care. Clin Chem 57(10):1357–1360PubMedCrossRefGoogle Scholar
  50. Hsich G, Kenney K, Gibbs CJ, Lee KH, Harrington MG (1996) The 14-3-3 brain protein in cerebrospinal fluid as a marker for transmissible spongiform encephalopathies. N Engl J Med 335(13):924–930PubMedCrossRefGoogle Scholar
  51. Hu Q, Noll RJ, Li H, Makarov A, Hardman M, Graham CR (2005) The Orbitrap: a new mass spectrometer. J Mass Spectrom 40(4):430–443PubMedCrossRefGoogle Scholar
  52. Hwang H, Bowen BP, Lefort N, Flynn CR, De Filippis EA, Roberts C, Smoke CC, Meyer C, Hojlund K, Yi Z, Mandarino LJ (2010) Proteomics analysis of human skeletal muscle reveals novel abnormalities in obesity and type 2 diabetes. Diabetes 59(1):33–42PubMedCrossRefGoogle Scholar
  53. Ibarrola N, Kalume DE, Gronborg M, Iwahori A, Pandey A (2003) A proteomic approach for quantitation of phosphorylation using stable isotope labeling in cell culture. Anal Chem 75(22):6043–6049PubMedCrossRefGoogle Scholar
  54. Ippel JH, Pouvreau L, Kroef T, Gruppen H, Versteeg G, Putten P van den, Struik PC, Mierlo CPM van (2004) In vivo uniform 15N-isotope labelling of plants: using the greenhouse for structural proteomics. Proteomics 4(1):226–234PubMedCrossRefGoogle Scholar
  55. Ishihama Y, Oda Y, Tabata T, Sato T, Nagasu T, Rappsilber J, Mann M (2005) Exponentially modified protein abundance index (emPAI) for estimation of absolute protein amount in proteomics by the number of sequenced peptides per protein. Mol Cell Proteomics 4(9):1265–1272PubMedCrossRefGoogle Scholar
  56. Jensen ON (2004) Modification-specific proteomics: characterization of post-translational modifications by mass spectrometry. Curr Opin Chem Biol 8(1):33–41PubMedCrossRefGoogle Scholar
  57. Keller A, Nesvizhskii AI, 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(20):5383–5392PubMedCrossRefGoogle Scholar
  58. Kim J, Choi YS, Lim S, Yea K, Yoon JH, Jun DJ, Ha SH, Kim JW, Kim JH, Suh PG, Ryu SH, Lee TG (2010) Comparative analysis of the secretory proteome of human adipose stromal vascular fraction cells during adipogenesis. Proteomics 10(3):394–405PubMedCrossRefGoogle Scholar
  59. Kratchmarova I, Kalume DE, Blagoev B, Scherer PE, Podtelejnikov AV, Molina H, Bickel PE, Andersen JS, Fernandez MM, Bunkenborg J, Roepstorff P, Kristiansen K, Lodish HF, Mann M, Pandey A (2002) A proteomic approach for identification of secreted proteins during the differentiation of 3T3-L1 preadipocytes to adipocytes. Mol Cell Proteomics 1(3):213–222PubMedCrossRefGoogle Scholar
  60. Krijgsveld J, Ketting, RF Mahmoudi T, Johansen J, Artal-Sanz M, Verrijzer CP, Plasterk RH, Heck AJ (2003) Metabolic labeling of C. elegans and D. melanogaster for quantitative proteomics. Nat Biotechnol 21(8):927–931PubMedCrossRefGoogle Scholar
  61. Kruger M, Kratchmarova I, Blagoev B, Tseng YH, Kahn CR, Mann M (2008) Dissection of the insulin signaling pathway via quantitative phosphoproteomics. Proc Natl Acad Sci U. S. A. 105(7):2451–2456PubMedCrossRefGoogle Scholar
  62. Kuster B, Schirle M, Mallick P, Aebersold R (2005) Scoring proteomes with proteotypic peptide probes. Nat Rev. Mol Cell Biol 6(7):577–583Google Scholar
  63. Lamers D, Famulla S, Wronkowitz N, Hartwig S, Lehr S, Ouwens DM, Eckardt K, Kaufman JM, Ryden M, Muller S, Hanisch FG, Ruige J, Arner P, Sell H, Eckel J (2011) Dipeptidyl peptidase 4 is a novel adipokine potentially linking obesity to the metabolic syndrome. Diabetes 60(7):1917–1925PubMedCrossRefGoogle Scholar
  64. Lanne B, Potthast F, Hoglund A, Brockenhuus LH von, Nystrom AC, Nilsson F, Dahllof B (2001) Thiourea enhances mapping of the proteome from murine white adipose tissue. Proteomics 1(7):819–828PubMedCrossRefGoogle Scholar
  65. Larsen TM, Dalskov SM, Baak M van, Jebb SA, Papadaki A, Pfeiffer AF, Martinez JA, Handjieva-Darlenska T, Kunesova M, Pihlsgard M, Stender S, Holst C, Saris WH, Astrup A (2010) Diets with high or low protein content and glycemic index for weight-loss maintenance. N Engl J Med 363(22):2102–2113PubMedCrossRefGoogle Scholar
  66. Lasonder E, Ishihama Y, Andersen JS, Vermunt AM, Pain A, Sauerwein RW, Eling WM, Hall N, Waters AP, Stunnenberg HG, Mann M (2002) Analysis of the Plasmodium falciparum proteome by high-accuracy mass spectrometry. Nature 419(6906):537–542PubMedCrossRefGoogle Scholar
  67. Legrain P, Aebersold R, Archakov A, Bairoch A, Bala K, Beretta L, Bergeron J, Borchers CH, Corthals GL, Costello CE, Deutsch EW, Domon B, Hancock W, He F, Hochstrasser D, Marko-Varga G, Salekdeh GH, Sechi S, Snyder M, Srivastava S, Uhlen M, Wu CH, Yamamoto T, Paik YK, Omenn GS (2011) The human proteome project: current state and future direction. Mol Cell Proteomics 10(7):M111PubMedGoogle Scholar
  68. Leptos KC, Sarracino DA, Jaffe JD, Krastins B, Church GM (2006) MapQuant: open-source software for large-scale protein quantification. Proteomics 6(6):1770–1782PubMedCrossRefGoogle Scholar
  69. Lescuyer P, Hochstrasser D, Rabilloud T (2007) How shall we use the proteomics toolbox for biomarker discovery? J Proteome Res 6(9):3371–3376PubMedCrossRefGoogle Scholar
  70. Li XJ, Yi EC, Kemp CJ, Zhang H, Aebersold R (2005) A software suite for the generation and comparison of peptide arrays from sets of data collected by liquid chromatography-mass spectrometry. Mol Cell Proteom 4:1328–1340 (Sep 2005)CrossRefGoogle Scholar
  71. Li RX, Chen HB, Tu K, Zhao SL, Zhou H, Li SJ, Dai J, Li QR, Nie S, Li YX, Jia WP, Zeng R, Wu JR (2008) Localized-statistical quantification of human serum proteome associated with type 2 diabetes. PLoS ONE (Electronic Resource) 3(9):e3224PubMedCrossRefGoogle Scholar
  72. Lisacek F, Cohen Boulakia S, Appel RD (2006) Proteome informatics II: Bioinformatics for comparative proteomics. Proteomics 6:5445–5466 (Oct 2006)PubMedCrossRefGoogle Scholar
  73. Liu HB, Sadygov RG, Yates JR III (2004) A model for random sampling and estimation of relative protein abundance in shotgun proteomics. Anal Chem 76(14):4193–4201PubMedCrossRefGoogle Scholar
  74. MacBeath G, Schreiber SL (2000) Printing proteins as microarrays for high-throughput function determination. Science 289(5485):1760–1763PubMedGoogle Scholar
  75. Mallick P, Kuster B (2010) Proteomics: a pragmatic perspective. Nat Biotechnol 28(7):695–709PubMedCrossRefGoogle Scholar
  76. Mallick P, Schirle M, Chen SS, Flory MR, Lee H, Martin D, Ranish J, Raught B, Schmitt R, Werner T, Kuster B, Aebersold R (2007) Computational prediction of proteotypic peptides for quantitative proteomics. Nat Biotechnol 25(1):125–131PubMedCrossRefGoogle Scholar
  77. Mann M, Hojrup P, Roepstorff P (1993) Use of mass spectrometric molecular weight information to identify proteins in sequence databases. Biol Mass Spectrom 22(6):338–345PubMedCrossRefGoogle Scholar
  78. Mann M, Wilm M (1994) Error-tolerant identification of peptides in sequence databases by peptide sequence tags. Anal Chem 66(24):4390–4399PubMedCrossRefGoogle Scholar
  79. Matthiesen R (2007) Methods, algorithms and tools in computational proteomics: a practical point of view. Proteomics 7(16):2815–2832PubMedCrossRefGoogle Scholar
  80. Matthiesen R, Lundsgaard M, Welinder KG, Bauw G (2003) Interpreting peptide mass spectra by VEMS. Bioinf 19(6):792–793CrossRefGoogle Scholar
  81. Matthiesen R, Bunkenborg J, Stensballe A, Jensen ON, Welinder KG, Bauw G (2004) Database-independent, database-dependent, and extended interpretation of peptide mass spectra in VEMS V2.0. Proteomics 4(9):2583–2593PubMedCrossRefGoogle Scholar
  82. Matthiesen R, Trelle MB, Hojrup P, Bunkenborg J, Jensen ON (2005) VEMS 3.0: algorithms and computational tools for tandem mass spectrometry based identification of post-translational modifications in proteins. J Proteome Res 4(6):2338–2347PubMedCrossRefGoogle Scholar
  83. Metz TO, Jacobs JM et al (2006) Characterization of the human pancreatic islet proteome by two-dimensional LC/MS/MS. J Proteome Res 5(12):3345–3354PubMedCrossRefGoogle Scholar
  84. Mueller LN, Rinner O, Schmidt A, Letarte S, Bodenmiller B, Brusniak MY, Vitek O, Aebersold R, Muller M (2007) SuperHirn—a novel tool for high resolution LC-MS-based peptide/protein profiling. Proteomics 7(19):3470–3480PubMedCrossRefGoogle Scholar
  85. Nesvizhskii AI, Keller A, Kolker E, Aebersold R (2003) A statistical model for identifying proteins by tandem mass spectrometry. Anal Chem 75(17):4646–4658PubMedCrossRefGoogle Scholar
  86. Norbeck AD, Monroe ME, Adkins JN, Anderson KK, Daly DS, Smith RD (2005) The utility of accurate mass and LC elution time information in the analysis of complex proteomes. J Am Soc Mass Spectrom 16(8):1239–1249PubMedCrossRefGoogle Scholar
  87. Ong SE, Blagoev B, Kratchmarova I, Kristensen DB, Steen H, Pandey A, Mann M (2002) Stable isotope labeling by amino acids in cell culture, SILAC, as a simple and accurate approach to expression proteomics. Mol Cell Proteomics 1(5):376–386PubMedCrossRefGoogle Scholar
  88. Palagi PM, Walther D, Quadroni M, Catherinet S, Burgess J, Zimmermann Ivol CG, Sanchez JC, Binz PA, Hochstrasser DF, Appel RD (2005) MSight: an image analysis software for liquid chromatography-mass spectrometry. Proteomics 5:2381–2384 (Jun 2005)PubMedCrossRefGoogle Scholar
  89. Palmblad M, Ramstrom M, Bailey CG, McCutchen-Maloney SL, Bergquist J, Zeller LC (2004) Protein identification by liquid chromatography-mass spectrometry using retention time prediction. J Chromatogr B Analyt Technol Biomed Life Sci 803(1):131–135PubMedCrossRefGoogle Scholar
  90. Panchaud A, Hansson J, Affolter M, Rhlid RB, Piu S, Moreillon P, Kussmann M (2008) ANIBAL—stable-isotope-based quantitative proteomics by ANIline and Benzoic acid labeling of amino and carboxylic groups. Mol Cell Proteomics 7(4):800–812Google Scholar
  91. Panchaud A, Scherl A, Shaffer SA, Haller PD von, Kulasekara HD, Miller SI, Goodlett DR (2009) Precursor acquisition independent from ion count: how to dive deeper into the proteomics ocean. Anal Chem 81(15):6481–6488PubMedCrossRefGoogle Scholar
  92. Panchaud A, Jung S, Shaffer SA, Aitchison JD, Goodlett DR (2011) Faster, quantitative, and accurate precursor acquisition independent from ion count. Anal Chem 83(6):2250–2257PubMedCrossRefGoogle Scholar
  93. Peng J, Elias JE, Thoreen CC, Licklider LJ, Gygi SP (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(1):43–50PubMedCrossRefGoogle Scholar
  94. Perez-Perez R, Ortega-Delgado FJ, Garcia-Santos E, Lopez JA, Camafeita E, Ricart W, Fernandez-Real JM, Peral B (2009) Differential proteomics of omental and subcutaneous adipose tissue reflects their unalike biochemical and metabolic properties. J Proteome Res 8(4):1682–1693PubMedCrossRefGoogle Scholar
  95. Perkins DN, Pappin DJ, Creasy DM, Cottrell JS (1999) Probability-based protein identification by searching sequence databases using mass spectrometry data. Electrophoresis 20(18):3551–3567PubMedCrossRefGoogle Scholar
  96. Pratt JM, Simpson DM, Doherty MK, Rivers J, Gaskell SJ, Beynon RJ (2006) Multiplexed absolute quantification for proteomics using concatenated signature peptides encoded by QconCAT genes. Nat Protocols 1(2):1029–1043CrossRefGoogle Scholar
  97. Ptacek J, Devgan G, Michaud G, Zhu H, Zhu X, Fasolo J, Guo H, Jona G, Breitkreutz A, Sopko R, McCartney RR, Schmidt MC, Rachidi N, Lee SJ, Mah AS, Meng L, Stark MJ, Stern DF, De VC, Tyers M, Andrews B, Gerstein M, Schweitzer B, Predki PF, Snyder M (2005) Global analysis of protein phosphorylation in yeast. Nature 438(7068):679–684PubMedCrossRefGoogle Scholar
  98. Rao PV, Reddy AP, Lu X, Dasari S, Krishnaprasad A, Biggs E, Roberts CT, Nagalla SR (2009) Proteomic identification of salivary biomarkers of type-2 diabetes. J Proteome Res 8(1):239–245PubMedCrossRefGoogle Scholar
  99. Rappsilber J, Ryder U, Lamond AI, Mann M (2002) Large-scale proteomic analysis of the human spliceosome. Genome Res 12(8):1231–1245PubMedCrossRefGoogle Scholar
  100. Raymond F, Metairon S, Borner R, Hofmann M, Kussmann M (2006) Automated target preparation for microarray-based gene expression analysis. Anal Chem 78(18):6299–6305PubMedCrossRefGoogle Scholar
  101. Riaz S, Skinner V, Srai SK (2011) Effect of high dose thiamine on the levels of urinary protein biomarkers in diabetes mellitus type 2. J Pharm Biomed Anal 54(4):817–825PubMedCrossRefGoogle Scholar
  102. Righetti PG, Boschetti E (2007) Sherlock Holmes and the proteome—a detective story. FEBS J 274(4):897–905PubMedCrossRefGoogle Scholar
  103. Righetti PG, Boschetti E, Lomas L, Citterio A (2006) Protein equalizer technology: the quest for a “democratic proteome”. Proteomics 6(14):3980–3992PubMedCrossRefGoogle Scholar
  104. Righetti PG, Castagna A, Antonioli P, Boschetti E (2005) Prefractionation techniques in proteome analysis: the mining tools of the third millennium. Electrophoresis 26(2):297–319PubMedCrossRefGoogle Scholar
  105. Ross PL, Huang YN, Marchese JN, Williamson B, Parker K, Hattan S, Khainovski N, Pillai S, Dey S, Daniels S, Purkayastha S, Juhasz P, Martin S, Bartlet-Jones M, He F, Jacobson A, Pappin DJ (2004) Multiplexed protein quantitation in saccharomyces cerevisiae using amine-reactive isobaric tagging reagents. Mol Cell Proteomics 3(12):1154–1169PubMedCrossRefGoogle Scholar
  106. Rubio-Aliaga I, Marvin-Guy LF, Wang P, Wagniere S, Mansourian R, Fuerholz A, Saris WH, Astrup A, Mariman EC, Kussmann M (2011) Mechanisms of weight maintenance under high- and low-protein, low-glycaemic index diets. Mol Nutr Food Res 55(11):1603–1612PubMedCrossRefGoogle Scholar
  107. Sanchez JC, Chiappe D, Converset V, Hoogland C, Binz PA, Paesano S, Appel RD, Wang S, Sennitt M, Nolan A, Cawthorne MA, Hochstrasser DF (2001) The mouse SWISS-2D PAGE database: a tool for proteomics study of diabetes and obesity. Proteomics 1(1):136–163PubMedCrossRefGoogle Scholar
  108. Sanchez JC, Converset V, Nolan A, Schmid G, Wang S, Heller M, Sennitt MV, Hochstrasser DF, Cawthorne MA (2003) Effect of rosiglitazone on the differential expression of obesity and insulin resistance associated proteins in lep/lep mice. Proteomics 3(8):1500–1520PubMedCrossRefGoogle Scholar
  109. Sanders SL, Jennings J, Canutescu A, Link AJ, Weil PA (2002) Proteomics of the eukaryotic transcription machinery: identification of proteins associated with components of yeast TFIID by multidimensional mass spectrometry. Mol Cell Biol 22(13):4723–4738PubMedCrossRefGoogle Scholar
  110. Schena M, Shalon D, Davis RW, Brown PO (1995) Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science 270(5235):467–470PubMedCrossRefGoogle Scholar
  111. Scherl A, Shaffer SA, Taylor GK, Kulasekara HD, Miller SI, Goodlett DR (2008) Genome-specific gas-phase fractionation strategy for improved shotgun proteomic profiling of proteotypic peptides. Anal Chem 80(4):1182–1191PubMedCrossRefGoogle Scholar
  112. Schlatzer DM, Dazard JE, Dharsee M, Ewing RM, Ilchenko S, Stewart I, Christ G, Chance MR (2009) Urinary protein profiles in a rat model for diabetic complications. Mol Cell Proteomics 8(9):2145–2158PubMedCrossRefGoogle Scholar
  113. Schmidt A, Kellermann J, Lottspeich F (2005) A novel strategy for quantitative proteomics using isotope-coded protein labels. Proteomics 5(1):4–15PubMedCrossRefGoogle Scholar
  114. Schrimpe-Rutledge AC, Fontes G, Gritsenko MA, Norbeck AD, Anderson DJ, Waters KM, Adkins JN, Smith RD, Poitout V (2012) Discovery of novel glucose-regulated proteins in isolated human pancreatic islets using LC-MS/MS-based proteomics. J Proteome Res 11(7):3520–3532PubMedCrossRefGoogle Scholar
  115. Singh LP, Jiang Y, Cheng DW (2007) Proteomic identification of 14-3-3zeta as an adapter for IGF-1 and Akt/GSK-3beta signaling and survival of renal mesangial cells. Int J Biol Sci 3(1):27–39CrossRefGoogle Scholar
  116. Starkey JM, Zhao Y, Sadygov RG, Haidacher SJ, Lejeune WS, Dey N, Luxon BA, Kane MA, Napoli JL, Denner L, Tilton RG (2010) Altered retinoic acid metabolism in diabetic mouse kidney identified by O isotopic labeling and 2D mass spectrometry. PLoS ONE (Electronic Resource) 5(6):e11095PubMedCrossRefGoogle Scholar
  117. Sunyaev S, Liska AJ, GolodA, Shevchenko A, Shevchenko A (2003) MultiTag: multiple error-tolerant sequence tag search for the sequence-similarity identification of proteins by mass spectrometry. Anal Chem 75(6):1307–1315PubMedCrossRefGoogle Scholar
  118. Surinova S, Schiess R, Huttenhain R, Cerciello F, Wollscheid B, Aebersold R (2011) On the development of plasma protein biomarkers. J Proteome Res 10(1):5–16PubMedCrossRefGoogle Scholar
  119. Suss C, Czupalla C, Winter C, Pursche T, Knoch KP, Schroeder M, Hoflack B, Solimena M (2009) Rapid changes of mRNA-binding protein levels following glucose and 3-isobutyl-1-methylxanthine stimulation of insulinoma INS-1 cells. Mol Cell Proteomics 8(3):393–408PubMedCrossRefGoogle Scholar
  120. Syka JE, Coon JJ, Schroeder MJ, Shabanowitz J, Hunt DF (2004a) Peptide and protein sequence analysis by electron transfer dissociation mass spectrometry. Proc Natl Acad Sci U. S. A. 101(26):9528–9533Google Scholar
  121. Syka JE, Marto JA, Bai DL, Horning S, Senko MW, Schwartz JC, Ueberheide B, Garcia B, Busby S, Muratore T, Shabanowitz J, Hunt DF (2004b) Novel linear quadrupole ion trap/FT mass spectrometer: performance characterization and use in the comparative analysis of histone H3 post-translational modifications. J Proteome Res 3(3):621–626CrossRefGoogle Scholar
  122. Tabb DL, Saraf A, Yates JR III (2003) GutenTag: high-throughput sequence tagging via an empirically derived fragmentation model. Anal Chem 75(23):6415–6421PubMedCrossRefGoogle Scholar
  123. Tilton RG, Haidacher SJ, Lejeune WS, Zhang X, Zhao Y, Kurosky A, Brasier AR, Denner L (2007) Diabetes-induced changes in the renal cortical proteome assessed with two-dimensional gel electrophoresis and mass spectrometry. Proteomics 7(10):1729–1742PubMedCrossRefGoogle Scholar
  124. Varghese SA, Powell TB, Budisavljevic MN, Oates JC, Raymond JR, Almeida JS, Arthur JM (2007) Urine biomarkers predict the cause of glomerular disease. J Am Soc Nephrol 18(3):913–922PubMedCrossRefGoogle Scholar
  125. Wallace DC (1999) Mitochondrial diseases in man and mouse. Science 283(5407):1482–1488PubMedCrossRefGoogle Scholar
  126. Wang Y, Lam KS, Lam JB, Lam MC, Leung PT, Zhou M, Xu A (2007) Overexpression of angiopoietin-like protein 4 alters mitochondria activities and modulates methionine metabolic cycle in the liver tissues of db/db diabetic mice. Mol Endocrinol 21(4):972–986PubMedCrossRefGoogle Scholar
  127. Wang P, Holst C, Andersen MR, Astrup A, Bouwman FG, Otterdijk S van, Wodzig WK, Baak MA van, Larsen TM, Jebb SA, Kafatos A, Pfeiffer AF, Martinez JA, Handjieva-Darlenska T, Kunesova M, Saris WH, Mariman EC (2011a) Blood profile of proteins and steroid hormones predicts weight change after weight loss with interactions of dietary protein level and glycemic index. PLoS. One 6(2):e16773CrossRefGoogle Scholar
  128. Wang P, Holst C, Astrup A, Bouwman FG, Otterdijk S van, Wodzig WK, Andersen MR, Baak MA van, Rasmussen LG, Alfredo MJ, Jebb SA, Pfeiffer AF, Kafatos A, Handjieva-Darlenska T, Hlavaty P, Saris WH, Mariman EC (2012) Blood profiling of proteins and steroids during weight maintenance with manipulation of dietary protein level and glycaemic index. Br J Nutr 107: 106–119Google Scholar
  129. Wang QM, Yang H, Tian DR, Cai Y, Wei ZN, Wang F, Yu AC, Han JS (2011b) Proteomic analysis of rat hypothalamus revealed the role of ubiquitin-proteasome system in the genesis of DR or DIO. Neurochem Res 36(6):939–946CrossRefGoogle Scholar
  130. Washburn MP, Wolters D, Yates JR III (2001) Large-scale analysis of the yeast proteome by multidimensional protein identification technology. Nat Biotechnol 19(3):242–247PubMedCrossRefGoogle Scholar
  131. Wollscheid B, Bausch-Fluck D, Henderson C, O’Brien R, Bibel M, Schiess R, Aebersold R, Watts JD (2009) Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins. Nat Biotechnol 27(4):378–386PubMedCrossRefGoogle Scholar
  132. Wu CC, MacCoss MJ, Howell KE, Matthews DE, Yates JR III (2004) Metabolic labeling of mammalian organisms with stable isotopes for quantitative proteomic analysis. Anal Chem 76(17):4951–4959PubMedCrossRefGoogle Scholar
  133. Zhang D, Yang H, Kong X, Wang K, Mao X, Yan X, Wang Y, Liu S, Zhang X, Li J, Chen L, Wu J, Wei M, Yang J, Guan Y (2011) Proteomics analysis reveals diabetic kidney as a ketogenic organ in type 2 diabetes. Am J Physiol Endocrinol Metab 300(2):E287–E295PubMedCrossRefGoogle Scholar
  134. Zhen Y, Xu N, Richardson B, Becklin R, Savage JR, Blake K, Peltier JM (2004) Development of an LC-MALDI method for the analysis of protein complexes. J Am Soc Mass Spectrom 15(6):803–822PubMedCrossRefGoogle Scholar
  135. Zhou H, Xiao Y, Li R, Hong S, Li S, Wang L, Zeng R, Liao K (2009) Quantitative analysis of secretome from adipocytes regulated by insulin. Acta Biochim Biophys Sin 41(11):910–921PubMedCrossRefGoogle Scholar
  136. Zubarev RA, Hakansson P, Sundqvist B (1996) Accuracy requirements for peptide characterization by monoisotopic molecular mass measurements. Anal Chem 68(22):4060–4063CrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  • Isabel Rubio-Aliaga
    • 1
  • Irma Silva-Zolezzi
    • 1
  • Michael Affolter
    • 1
  • Loïc Dayon
    • 2
  • Alexandre Panchaud
    • 1
  • Martin Kussmann
    • 2
    • 3
    • 4
    Email author
  1. 1.BioAnalytical Science DepartmentNestlé Research CentreLausanneSwitzerland
  2. 2.Molecular Biomarkers CoreNestlé Institute of Health Sciences SALausanneSwitzerland
  3. 3.Faculty of Life SciencesEcole Polytechnique Fédérale Lausanne (EPFL)LausanneSwitzerland
  4. 4.Faculty of ScienceAarhus UniversityAarhusDenmark

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