Skip to main content
SpringerLink
Log in

Variability of the healthy human proteome

  • Published:
Biochemistry (Moscow) Supplement Series B: Biomedical Chemistry Aims and scope Submit manuscript

Abstract

The aim of this review is to analyze results of studies on characteristics of protein variability and diversity of posttranslational modifications of proteins in healthy humans. Numerous studies have demonstrated that a proteomic profile is characterized by significant intra- and inter-individual variability, and quite often natural (“normal”) variability of some proteins can be comparable to changes observed in pathological processes. Results obtained by our research group have demonstrated high intra-individual variability of serum low-molecular subproteome of healthy volunteers, certified by a special medial committee (the coefficient of variation (CV) of 42.6%). The proteins characterized by high variability under normal conditions (e.g. haptoglobin — 0–40 mg/ml; lysozyme — 0.01–0.1 mg/ml; C-reactive protein — 0.01–0.3 mg/ml) cannot be considered as potential biomarkers of diseases. On the contrary, proteins and peptides characterized by insignificant dispersion in healthy population (such as albumin ( CV = 9%); transferrin-(CV = 14%); C3c complement (CV = 17%), α-1 acid glycoprotein (CV = 21%), α-2-macroglobulin (CV = 20%); transthyretin fragment (CV = 28.3%) and α2-HS-glycoprotein βchain (CV = 29.7%)) can provide valuable information about the state of health. Thus, studies of plasticity in the proteomic profiles of healthy humans will help to correct reference intervals used in clinical proteomics.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Diamandis, E.P., Lancet, 2002, vol. 360, pp. 170–171.

    Article  CAS  Google Scholar 

  2. Petricoin, E.F., Ardekani, A.M., and Hitt, B.A., Lancet, vol. 359, pp. 572–577.

  3. Moshkovskii, S.A., Serebryakova, M.V., Kuteykin-Teplyakov, K.B., Tikhonova, O.V., Goufman, E.I., Zgoda, V.G., Taranets, I.N., Makarov, O.V., and Archakov, A.I., Proteomics, 2006, vol. 5, pp. 3790–3797.

    Article  Google Scholar 

  4. Diamandis, E.P., J. Natl. Cancer Inst., 2003, vol. 95, pp. 489–490.

    Article  CAS  Google Scholar 

  5. Vlahou, A., Gregory, B., Wright, J., Gregory, B., Fournier, K., McGaughey, D., Perry, R.R., Wright, G.L. Jr., and Semmes, O.J., Clin. Breast Cancer, 2003, vol. 4, pp. 203–209.

    Article  CAS  Google Scholar 

  6. Koopmann, J., Zhang, Z., White, N., Rosenzweig, J., Fedarko, N., Jagannath, S., Canto, M.I., Yeo, C.J., Chan, D.W., and Goggins, M., Clin. Cancer Res., 2004, vol. 10, pp. 860–868.

    Article  CAS  Google Scholar 

  7. Engwegen, J.Y., Helgason, H.H., Cats, A., Harris, N., Bonfrer, J.M., Schellens, J.H., Beijnen, J.H., World J. Gastroenterol., 2006, vol. 12, pp. 1536–1544.

    CAS  Google Scholar 

  8. Engwegen, J.Y., Depla, A.C., Smith, M.E., Cats, A., Tuynman, H., van Heukelem, H.A., Snel, P., Meuleman, W., Wessels, L.F., Schellens, J.H., and Beijnen, J.H., Biomarker Insights, 2008, vol. 2, pp. 375–385.

    Google Scholar 

  9. Miguet, L., Bogumil, R., Decloquement, P., Herbrecht, R., Potier, N., Mauvieux, L., and Van Dorsselaer, A., J. Proteome Res., 2006, vol. 5, pp. 2258–2269.

    Article  CAS  Google Scholar 

  10. Zheng, P.P., Luider, T.M., Pieters, R., Avezaat, C.J., van den Bent, M.J., Sillevis Smitt, P.A., and Kros, J.M., J. Neuropathol. Exp. Neurol., 2003, vol. 62, pp. 855–862.

    CAS  Google Scholar 

  11. Carrette, O., Demalte, I., Scherl, A., Yalkinoglu, O., Corthals, G., Burkhard, P., Hochstrasser, D.F., and Sanchez, J.C., Proteomics, 2003, vol. 3, pp. 1486–1494.

    Article  CAS  Google Scholar 

  12. Guillaume, E., Zimmerman, C., Burkhard, P.R., Hochstrasser, D.F., and Sanchez, J.C., Proteomics, 2003, vol. 3, pp. 1495–1499.

    Article  CAS  Google Scholar 

  13. Sorace, J.M. and Zhan, M., BMC Bioinformatics, 2003, vol. 9, pp. 4–24.

    Google Scholar 

  14. Baggerly, K.A., Morris, J.S., Edmonson, S.R., and Coombes, K.R., J. Natl. Cancer Inst., 2005, vol. 97, pp. 307–309.

    Article  CAS  Google Scholar 

  15. Rai, A.J., Stemmer, P.M., Zhang, Z., Adam, B.L., Morgan, W.T., Caffrey, R. E., Podust, V.N., Patel, M., Lim, L.Y., Shipulina, N.V., Chan, D.W., Semmes, O.J., and Leung, H.C., Proteomics, 2005, vol. 5, pp. 3467–3474.

    Article  CAS  Google Scholar 

  16. Semmes, O.J., Feng, Z., Adam, B.L., Banez, L.L., Bigbee, W.L., Campos, D., Cazares, L.H., Chan, D.W., Grizzle, W.E., Izbicka, E., Kagan, J., Malik, G., McLerran, D., Moul, J.W., Partin, A., Prasanna, P., Rosenzweig, J., Sokoll, L.J., Srivastava, S., Thompson, I., Welsh, M.J., White, N., Winget, M., Yasui, Y., Zhang, Z., and Zhu, L., Clin. Chem., 2005, vol. 51, pp. 102–112.

    Article  CAS  Google Scholar 

  17. Whiteaker, J.R., Zhang, H., Eng, J.K., Fang, R., Piening, B.D., Feng, L.C., Lorentzen, T.D., Schoenherr, R.M., Keane, J.F., Holzman, T., Fitzgibbon, M., Lin, C., Zhang, H., Cooke, K., Liu, T., Camp, D.G., 2nd, Anderson, L., Watts, J., Smith, R.D., McIntosh, M.W., and Paulovich, A.G., J. Proteome Res., 2007, vol. 6, pp. 828–836.

    Article  CAS  Google Scholar 

  18. Baumann, S., Ceglarek, U., Fiedler, J.M., Lembcke, J., Leichtle, A., and Thiery, J., Clin. Chem., 2005, vol. 51, pp. 973–980.

    Article  CAS  Google Scholar 

  19. Tiss, A., Smith, C., Camuzeaux, S., Kabir, M., Gayther, S., Menon, U., Waterfield, M., Timms, J., Jacobs, I., and Cramer, R., Practical Proteomics, 2007, vol. 7,Suppl. 1, pp. 77–89.

    Article  Google Scholar 

  20. Ransohoff, D.F., J. Natl. Cancer Inst., 2005, vol. 97, pp. 315–319.

    Article  CAS  Google Scholar 

  21. Diamandis, E.P., Clin. Chem., 2003, vol. 49, pp. 1272–1275.

    Article  CAS  Google Scholar 

  22. Diamandis, E.P., J. Natl. Cancer Inst., 2004, vol. 96, pp. 353–356.

    Article  Google Scholar 

  23. Diamandis, E.P., Mol. Cell. Proteomics, 2004, vol. 3, pp. 367–378.

    Article  CAS  Google Scholar 

  24. Coombes, K.R., Morris, J.S., Hu, J., Edmonson, S.R., and Baggerly, K.A., Nat. Biotechnol., 2005, vol. 23, pp. 291–292.

    Article  CAS  Google Scholar 

  25. Diamandis, E.P., Expert Rev. Mol. Diagn., 2004, vol. 4, pp. 575–577.

    Article  Google Scholar 

  26. Nelsestuen, G.L., Zhang, Y., Martinez, M.B., Key, N.S., Jilma, B., Verneris, M., Sinaiko, A., and Kasthuri, R.S., Proteomics, 2005, vol. 5, pp. 4012–4024.

    Article  CAS  Google Scholar 

  27. Anderson, N.L. and Anderson, N.G., Mol. Cell. Proteomics, 2002, vol. 1, pp. 845–867.

    Article  CAS  Google Scholar 

  28. Nielsen, M.L., Savitski, M.M., and Zubarev, R.A., Mol. Cell. Proteomics, 2006, vol. 5, pp. 2384–2391.

    Article  CAS  Google Scholar 

  29. Nedelkov, D., Expert Rev. Proteomics, 2006, vol. 3, pp. 631–640.

    Article  CAS  Google Scholar 

  30. Nedelkov, D., Tubbs, K.A., Niederkofler, E.E., Kiernan, U.A., and Nelson, R.W., Anal. Chem., 2004, vol. 76, pp. 1733–1737.

    Article  CAS  Google Scholar 

  31. Nedelkov, D., Expert Rev. Proteomics, 2005, vol. 2, pp. 315–324.

    Article  CAS  Google Scholar 

  32. Nedelkov, D., Phillips, D.A., Tubbs, K.A., and Nelson, R.W., Mol. Cell. Proteomics, 2007, vol. 6, pp. 1183–1187.

    Article  CAS  Google Scholar 

  33. Nedelkov, D., Proteomics, 2008, vol. 8, pp. 779–786.

    Article  CAS  Google Scholar 

  34. Mirza, S.P. and Olivier, M., Physiol. Genomics, 2008, vol. 33, pp. 3–11.

    Article  CAS  Google Scholar 

  35. Farley, A.R. and Link, A.J., Methods Enzymol., 2009, vol. 463, pp. 725–763.

    Article  CAS  Google Scholar 

  36. Blackburn, K. and Goshe, M.B., Brief. Funct. Genomics, 2009, vol. 8, pp. 90–103.

    Article  CAS  Google Scholar 

  37. Connors, L.H., Lim, A., Prokaeva, T., Roskens, V.A., and Costello, C.E., Amyloid, 2003, vol. 10, pp. 160–184.

    Article  CAS  Google Scholar 

  38. Mahley, R.W. and Huang, Y., Curr. Opin. Lipidol., 1999, vol. 10, pp. 207–217.

    Article  CAS  Google Scholar 

  39. Biron, D.G., Loxdale, H.D., Ponton, F., Moura, H., Marché, L., Brugidou, C., and Thomas, F., Proteomics, 2006, vol. 6, pp. 1712–1715.

    Article  CAS  Google Scholar 

  40. Asirvatham, V.S., Watson, B.S., and Sumner, L.W., Proteomics, 2002, vol. 2, pp. 960–968.

    Article  CAS  Google Scholar 

  41. Jorge, I., Navarro, R.M., Lenz, C., Ariza, D., Porras, C., and Jorrin, J., Proteomics, 2005, vol. 5, pp. 222–234.

    Article  CAS  Google Scholar 

  42. Ramirez-Boo, M., Garrido, J.J., Ogueta, S., Calvete, J.J., Gomez-Diaz, C., and Moreno, A., Proteomics, 2006, vol. 6, pp. S215–S225.

    Article  Google Scholar 

  43. Molloy, M.P., Brzezinski, E.E., Hang, J., McDowell, M.T., and Van Bogelen, R.A., Proteomics, 2003, vol. 3, pp. 1912–1919.

    Article  CAS  Google Scholar 

  44. Zhang, X., Guo, Y., Song, Y., Sun, W., Yu, C., Zhao, X., Wang, H., Jiang, H., Li, Y., Qian, X., Jiang, Y., and He, F., Proteomics, 2006, vol. 6, pp. 5260–5268.

    Article  CAS  Google Scholar 

  45. Sanchez, J.C., Schaller, D., Ravier, F., Golaz, O., Jaccoud, S., Belet, M., Wilkins, M.R., James, R., Deshusses, J., and Hochstrasser, D., Electrophoresis, 1997, vol. 18, pp. 150–155.

    Article  CAS  Google Scholar 

  46. Hu, Y., Malone, J.P., Fagan, A.M., Townsend, R.R., and Holtzman, D.M., Mol. Cell. Proteomics, 2005, vol. 4, pp. 2000–2009.

    Article  CAS  Google Scholar 

  47. Winkler, W., Zellner, M., Diestinger, M., Babeluk, R., Marchetti, M., Goll, A., Zehetmayer, S., Bauer, P., Rappold, E., Miller, I., Roth, E., Allmaier, G., and Oehler, R., Mol. Cell Proteomics, 2008, vol. 7, pp. 193–203.

    CAS  Google Scholar 

  48. Corzett, T.H., Fodor, I.K., Choi, M.W., Walsworth, V.L., Turteltaub, K.W., McCutchen-Maloney, S.L., and Chromy, B.A., J. Biomed. Biotechnol., 2010, doi: 10.1155/2010/258494, Epub 2010 Jan 14.

  49. Pakharukova, N.A., Pastushkova, L.Kh., Trifonova, O.P., Moshkovskii, S.A., and Larina, I.M., Fiziol. Chel., 2011, vol. 37, no. 2, pp. 1–9.

    Google Scholar 

  50. http://apps.who.int/gb/bd/PDF/bd47/RU/constitution-ru.pdf

  51. Willams, R., Biokhimicheskaya individualnost’: osnovy genetotrofnoi contceptsii (Biochemical Individuality: Principles of Genetotrophic Concept), Moscow: Inostrannaya Literatura, 1960.

    Google Scholar 

  52. Korol’kov, A.A., Dialektika i teoreticheskaya meditsina (Dialectics and Theoretical Medicine), Moscow: Meditsina, 1979.

    Google Scholar 

  53. Grigoriev, A.I. and Baevskii, R.M., Kontseptsiya zdorov’ya i problema normy v kosmicheskoi meditsine (The Concepts of Health and the Problem of the Norm in Space Medicine), Moscow: Slovo, 2001.

    Google Scholar 

  54. Shmal’gauzen, I.I., Vestn. AMN SSSR, 1975, no. 10, pp. 5–16.

  55. Voshol, H., Glucksman, M.J., and van Oostrum, J., Curr. Mol. Med., 2003, vol. 3, pp. 447–458.

    Article  CAS  Google Scholar 

  56. Tuxen, M.K., Sölétormos, G., Petersen, P.H., Schioler, V., and Dombernowsky, P., Gynecol. Oncol., 1999, vol. 74, pp. 12–22.

    Article  CAS  Google Scholar 

  57. Erden, G., Barazi, A.O., Tezcan, G., and Yildirimkaya, M.M., Scand. J. Clin. Lab. Invest., 2008, vol. 68, pp. 212–218.

    Article  CAS  Google Scholar 

  58. Hortin, G.L., Sviridov, D., and Anderson, N.L., Clin. Chem., 2008, vol. 54, pp. 1608–1616.

    Article  CAS  Google Scholar 

  59. Campbell, B., Badrick, T., Flatman, R., and Kanowski, D., Ann. Clin. Biochem., 2002, vol. 39,Pt 2, pp. 85–88.

    Article  CAS  Google Scholar 

  60. Macy, E.M., Hayes, T.E., and Tracy, R.P., Clin. Chem., 1997, vol. 43, pp. 52–58.

    CAS  Google Scholar 

  61. Clark, G.H. and Fraser, C.G., Ann. Clin. Biochem., 1993, vol. 39, pp. 373–376.

    Google Scholar 

  62. Huguet, J. and Fuentes-Arderiu, X., Scand. J. Clin. Lab. Invest., 1991, vol. 51, pp. 735–738.

    Article  CAS  Google Scholar 

  63. Hyltoft Petersen, P., Feldt-Rasmussen, U., Hörder, M., Blaabjerg, O., and Thygesen, K., Scand. J. Clin. Lab. Invest., 1981, vol. 41, pp. 143–150.

    Article  CAS  Google Scholar 

  64. Anesi, A., Rondanelli, M., Trotti, R., and Melzi d’Eril, G.V., Aging (Milano), 2000, vol. 12, pp. 168–172.

    CAS  Google Scholar 

  65. Buckley, C.E. and Dorsey III, F.C., J. Immunol., 1970, vol. 105, pp. 964–972.

    CAS  Google Scholar 

  66. Denko, C.W. and Gabriel, P., Ann. Clin. Lab. Sci., 1981, vol. 11, pp. 63–68.

    CAS  Google Scholar 

  67. Poortmans, J.R. and Haralambie, G., Eur. J. Appl. Physiol. Occup. Physiol., 1979, vol. 40, pp. 245–254.

    Article  CAS  Google Scholar 

  68. Hyltoft Petersen, P., Felding, P., Hörder, M., and Tryding, N., Scand. J. Clin. Lab. Invest., 1980, vol. 40, pp. 623–628.

    Article  CAS  Google Scholar 

  69. Linkowski, P., Spiegel, K., Kerkhofs, M., L’Hermite-Balériaux, M., Van Onderbergen, A., Leproult, R., Mendlewicz, J., and Van Cauter, E., Am. J. Physiol., 1998, vol. 274, pp. 909–919.

    Google Scholar 

  70. Balabolkin, M.I., Endokrinologiya (Endocrinology), Moscow: Universum Publishing, 1998.

    Google Scholar 

  71. Levin, Ya.I., Russ. Med. Zh., Nevrologiya i Psikhiatriya, 2007, vol. 15, pp. 1851–1855.

    Google Scholar 

  72. Blumenthal, G.M., Kohn, M.C., and Portier, C.J., Toxicol. Appl. Pharmacol., 1997, vol. 147, pp. 83–92.

    Article  CAS  Google Scholar 

  73. Larina, I.M., Morukov, B.V., and Grigoriev, A.I., Fiziol. Chel., 1999, vol. 25, no. 6, pp. 89–95.

    CAS  Google Scholar 

  74. Bruguerolle, B., Bouvenot, G., Arnaud, C., Lévy, F., Mechkouri, M., Bartolin, R., and Peronne, R., Rev. Rhum. Mal. Osteoartic., 1986, vol. 53, pp. 313–316.

    CAS  Google Scholar 

  75. Wiedermann, D., Kríz, J., and Cídl, K., Czech. Med., 1980, vol. 3, pp. 239–247.

    CAS  Google Scholar 

  76. Aldred, S., Sozzi, T., Mudway, I., Grant, M.M., Neubert, H., Kelly, F.J., and Griffiths, H.R., Proteomics, 2006, vol. 6, pp. 1695–1703.

    Article  CAS  Google Scholar 

  77. de Roos, B., Geelen, A., Ross, K., Rucklidge, G., Reid, M., Duncan, G., Caslake, M., Horgan, G., and Brouwer, I.A., Proteomics, 2008, vol. 8, pp. 1965–1974.

    Article  Google Scholar 

  78. Kang, M.J., Lee, D.Y., Joo, W.A., and Kim, C.W., J. Proteome Res., 2005, vol. 4, pp. 1248–1255.

    Article  CAS  Google Scholar 

  79. Joo, W.A., Sul, D., Lee, D.Y., and Kim, C.W., Mutat. Res., 2004, vol. 558, pp. 35–44.

    CAS  Google Scholar 

  80. Vermeulen, R., Lan, Q., Zhang, L., Gunn, L., McCarthy, D., Woodbury, R.L., McGuire, M., Podust, V.N., Li, G., Chatterjee, N., Mu, R., Yin, S., Rothman, N., and Smith, M.T., Proc. Natl. Acad. Sci. USA, 2005, vol. 102, pp. 1704–1716.

    Article  Google Scholar 

  81. Kap-Soon, N., Do-Youn, L., Hak, C.J., Joo, W.A., Lee, E, and Chan-Wha, K., Proteomics, 2004, vol. 4, pp. 3505–3513.

    Article  CAS  Google Scholar 

  82. Trifonova, O., Larina, I., Grigoriev, A., Lisitsa, A., Moshkovskii, S., and Archakov, A., Expert Rev. Proteomics, 2010, vol. 7, pp. 431–438.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. State Scientific Centre — Institute for Biomedical Problems, Russian Academy of Sciences, Khoroshevskoye sh. 76-a, Moscow, 123007, Russia

    N. A. Pakharukova, L. Kh. Pastushkova & I. M. Larina

  2. Institute of Biomedical Chemistry, Russian Academy of Medical Sciences, Moscow, Russia

    S. A. Moshkovskii

Authors
  1. N. A. Pakharukova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. L. Kh. Pastushkova
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. A. Moshkovskii
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. I. M. Larina
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to N. A. Pakharukova.

Additional information

Original Russian Text © N.A. Pakharukova, L.Kh. Pastushkova, S.A. Moshkovskii, I.M. Larina, 2011, published in Biomeditsinskaya Khimiya.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pakharukova, N.A., Pastushkova, L.K., Moshkovskii, S.A. et al. Variability of the healthy human proteome. Biochem. Moscow Suppl. Ser. B 5, 203–212 (2011). https://doi.org/10.1134/S1990750811030097

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1990750811030097

Keywords

Search

Navigation