Ukr.Biochem.J. 2013; Volume 85, Issue 6, Nov-Dec, pp. 8-17


Chromosomocentric approach to overcoming difficulties in implementation of international project Human Proteome

A. I. Archakov1, V. G. Zgoda1, A. T. Kopylov1, S. N. Naryzhny1,2,
A. L. Chernobrovkin1, E. A. Ponomarenko1, A. V. Lisitsa1

1V. N. Orekhovich Scientific-Research Institute  of Biomedical Chemistry, Russian Academy of Medical Sciences;
2Petersburg Nuclear Physics Institute at National  Research Centre Kurchatov Institute

The international project Human Proteome (PHP), being a logical continuation of the project Human Genome, was started on September 23, 2010. In correspondence with the genocentric approach, the PHP aim is to prepare a catalogue of all human proteins and to decipher a network of their interactions. The PHP implementation difficulties arise because the research subject itself – proteome – is much more complicated than genome. The major problem is the insufficient sensitivity of proteome methods that does not allow detecting low- and ultralow-copy proteins. Bad reproducibility of proteome methods and the lack of so-called “gold standard” is the second major complicacy in PHP implementation. The third problem is the dynamic character of proteome, its instabili­ty in time. The paper deals with possible variants of overcoming these complicacies, preventing from successful implementation of PHP.

Keywords: , , ,


  1. 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, Uhlén M, Wu CH, Yamamoto T, Paik YK, Omenn GS. The human proteome project: current state and future direction. Mol Cell Proteomics. 2011 Jul;10(7):M111.009993. PubMed, PubMedCentral, CrossRef
  2. Paik YK, Jeong SK, Omenn GS, Uhlen M, Hanash S, Cho SY, Lee HJ, Na K, Choi EY, Yan F, Zhang F, Zhang Y, Snyder M, Cheng Y, Chen R, Marko-Varga G, Deutsch EW, Kim H, Kwon JY, Aebersold R, Bairoch A, Taylor AD, Kim KY, Lee EY, Hochstrasser D, Legrain P, Hancock WS. The Chromosome-Centric Human Proteome Project for cataloging proteins encoded in the genome. Nat Biotechnol. 2012 Mar 7;30(3):221-3. PubMed, CrossRef
  3. Paik YK, Omenn GS, Uhlen M, Hanash S, Marko-Varga G, Aebersold R, Bairoch A, Yamamoto T, Legrain P, Lee HJ, Na K, Jeong SK, He F, Binz PA, Nishimura T, Keown P, Baker MS, Yoo JS, Garin J, Archakov A, Bergeron J, Salekdeh GH, Hancock WS. Standard guidelines for the chromosome-centric human proteome project. J Proteome Res. 2012 Apr 6;11(4):2005-13. PubMed, CrossRef
  4. The big ome. Nature. 2008 Apr 24;452(7190):913-4. PubMed, CrossRef
  5. A gene-centric human proteome project: HUPO–the Human Proteome organization. Mol Cell Proteomics. 2010 Feb;9(2):427-9. PubMed, PubMedCentral, CrossRef
  6. Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, Devon K, Dewar K, Doyle M, FitzHugh W et al. Initial sequencing and analysis of the human genome. Nature. 2001 Feb 15;409(6822):860-921. PubMed
  7. Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, Smith HO, Yandell M, Evans CA, Holt RA et al. The sequence of the human genome. Science. 2001 Feb 16;291(5507):1304-51. PubMed
  8. Voelkerding KV, Dames SA, Durtschi JD. Next-generation sequencing: from basic research to diagnostics. Clin Chem. 2009 Apr;55(4):641-58. Review. PubMed, CrossRef
  9. Snyder M, Du J, Gerstein M. Personal genome sequencing: current approaches and challenges. Genes Dev. 2010 Mar 1;24(5):423-31. PubMed, PubMedCentral, CrossRef
  10. Tejedor JR, Valcárcel J. Gene regulation: Breaking the second genetic code. Nature. 2010 May 6;465(7294):45-6. PubMed, CrossRef
  11. Via M, Gignoux C, Burchard EG. The 1000 Genomes Project: new opportunities for research and social challenges. Genome Med. 2010 Jan 21;2(1):3. PubMed, PubMedCentral, CrossRef
  12. Rosenbloom KR, Dreszer TR, Pheasant M, Barber GP, Meyer LR, Pohl A, Raney BJ, Wang T, Hinrichs AS, Zweig AS, Fujita PA, Learned K, Rhead B, Smith KE, Kuhn RM, Karolchik D, Haussler D, Kent WJ. ENCODE whole-genome data in the UCSC Genome Browser. Nucleic Acids Res. 2010 Jan;38(Database issue):D620-5. PubMed, PubMedCentral, CrossRef
  13. Nilsson T, Mann M, Aebersold R, Yates JR 3rd, Bairoch A, Bergeron JJ. Mass spectrometry in high-throughput proteomics: ready for the big time. Nat Methods. 2010 Sep;7(9):681-5. PubMed, CrossRef
  14. Nagaraj N, Wisniewski JR, Geiger T, Cox J, Kircher M, Kelso J, Pääbo S, Mann M. Deep proteome and transcriptome mapping of a human cancer cell line. Mol Syst Biol. 2011 Nov 8;7:548. PubMed, PubMedCentral, CrossRef
  15. Saiki RK, Gelfand DH, Stoffel S, Scharf SJ, Higuchi R, Horn GT, Mullis KB, Erlich HA. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487-91. PubMed, CrossRef
  16. Archakov AI, Ivanov YD, Lisitsa AV, Zgoda VG. AFM fishing nanotechnology is the way to reverse the Avogadro number in proteomics. Proteomics. 2007 Jan;7(1):4-9. PubMed, CrossRef
  17. Anderson NL, Anderson NG. The human plasma proteome: history, character, and diagnostic prospects. Mol Cell Proteomics. 2002 Nov;1(11):845-67. Review. PubMed
  18. Zgoda VG, Moshkovskii SA, Ponomarenko EA, Andreewski TV, Kopylov AT, Tikhonova OV, Melnik SA, Lisitsa AV, Archakov AI. Proteomics of mouse liver microsomes: performance of different protein separation workflows for LC-MS/MS. Proteomics. 2009 Aug;9(16):4102-5. PubMed, CrossRef
  19. Malmström J, Lee H, Nesvizhskii AI, Shteynberg D, Mohanty S, Brunner E, Ye M, Weber G, Eckerskorn C, Aebersold R. Optimized peptide separation and identification for mass spectrometry based proteomics via free-flow electrophoresis. J Proteome Res. 2006 Sep;5(9):2241-9. PubMed
  20. Washburn MP, Wolters D, Yates JR 3rd. Large-scale analysis of the yeast proteome by multidimensional protein identification technology. Nat Biotechnol. 2001 Mar;19(3):242-7. PubMed
  21. de Godoy LM, Olsen JV, de Souza GA, Li G, Mortensen P, Mann M. Status of complete proteome analysis by mass spectrometry: SILAC labeled yeast as a model system. Genome Biol. 2006;7(6):R50. PubMed, PubMedCentral
  22. Klose J. From 2-D electrophoresis to proteomics. Electrophoresis. 2009 Jun;30 Suppl 1:S142-9. PubMed, CrossRef
  23. Nedelkov D, Kiernan UA, Niederkofler EE, Tubbs KA, Nelson RW. Population proteomics: the concept, attributes, and potential for cancer biomarker research. Mol Cell Proteomics. 2006 Oct;5(10):1811-8. Review. PubMed
  24. Tran JC, Zamdborg L, Ahlf DR, Lee JE, Catherman AD, Durbin KR, Tipton JD, Vellaichamy A, Kellie JF, Li M, Wu C, Sweet SM, Early BP, Siuti N, LeDuc RD, Compton PD, Thomas PM, Kelleher NL. Mapping intact protein isoforms in discovery mode using top-down proteomics. Nature. 2011 Oct 30;480(7376):254-8. PubMed, PubMedCentral, CrossRef
  25. Kiyonami R, Schoen A, Prakash A, Peterman S, Zabrouskov V, Picotti P, Aebersold R, Huhmer A, Domon B. Increased selectivity, analytical precision, and throughput in targeted proteomics. Mol Cell Proteomics. 2011 Feb;10(2):M110.002931. PubMed, PubMedCentral, CrossRef
  26. Anderson L, Hunter CL. Quantitative mass spectrometric multiple reaction monitoring assays for major plasma proteins. Mol Cell Proteomics. 2006 Apr;5(4):573-88.  PubMed
  27. Keshishian H, Addona T, Burgess M, Kuhn E, Carr SA. Quantitative, multiplexed assays for low abundance proteins in plasma by targeted mass spectrometry and stable isotope dilution. Mol Cell Proteomics. 2007 Dec;6(12):2212-29. PubMed, PubMedCentral
  28. Keshishian H, Addona T, Burgess M, Mani DR, Shi X, Kuhn E, Sabatine MS, Gerszten RE, Carr SA. Quantification of cardiovascular biomarkers in patient plasma by targeted mass spectrometry and stable isotope dilution. Mol Cell Proteomics. 2009 Oct;8(10):2339-49. PubMed, PubMedCentral, CrossRef
  29. Stahl-Zeng J, Lange V, Ossola R, Eckhardt K, Krek W, Aebersold R, Domon B. High sensitivity detection of plasma proteins by multiple reaction monitoring of N-glycosites. Mol Cell Proteomics. 2007 Oct;6(10):1809-17. PubMed
  30. Whiteaker JR, Zhao L, Anderson L, Paulovich AG. An automated and multiplexed method for high throughput peptide immunoaffinity enrichment and multiple reaction monitoring mass spectrometry-based quantification of protein biomarkers. Mol Cell Proteomics. 2010 Jan;9(1):184-96. PubMed, PubMedCentral, CrossRef
  31. Unwin RD, Griffiths JR, Leverentz MK, Grallert A, Hagan IM, Whetton AD. Multiple reaction monitoring to identify sites of protein phosphorylation with high sensitivity. Mol Cell Proteomics. 2005 Aug;4(8):1134-44. PubMed
  32. Unwin RD, Griffiths JR, Whetton AD. A sensitive mass spectrometric method for hypothesis-driven detection of peptide post-translational modifications: multiple reaction monitoring-initiated detection and sequencing (MIDAS). Nat Protoc. 2009;4(6):870-7. PubMed, CrossRef
  33. Berle M, Kroksveen AC, Haaland OA, Aye TT, Opsahl JA, Oveland E, Wester K, Ulvik RJ, Helland CA, Berven FS. Protein profiling reveals inter-individual protein homogeneity of arachnoid cyst fluid and high qualitative similarity to cerebrospinal fluid. Fluids Barriers CNS. 2011 May 20;8:19. PubMed, PubMedCentral, CrossRef
  34. Sherwood CA, Eastham A, Lee LW, Peterson A, Eng JK, Shteynberg D, Mendoza L, Deutsch EW, Risler J, Tasman N, Aebersold R, Lam H, Martin DB. MaRiMba: a software application for spectral library-based MRM transition list assembly. J Proteome Res. 2009 Oct;8(10):4396-405. PubMed, PubMedCentral, CrossRef
  35. Reiter L, Rinner O, Picotti P, Hüttenhain R, Beck M, Brusniak MY, Hengartner MO, Aebersold R. mProphet: automated data processing and statistical validation for large-scale SRM experiments. Nat Methods. 2011 May;8(5):430-5. PubMed, CrossRef
  36. Archakov A, Aseev A, Bykov V, Grigoriev A, Govorun V, Ivanov V, Khlunov A, Lisitsa A, Mazurenko S, Makarov AA, Ponomarenko E, Sagdeev R, Skryabin K. Gene-centric view on the human proteome project: the example of the Russian roadmap for chromosome 18. Proteomics. 2011 May;11(10):1853-6. PubMed, CrossRef
  37. Archakov A, Ivanov Y, Lisitsa A, Zgoda V. Biospecific irreversible fishing coupled with atomic force microscopy for detection of extremely low-abundant proteins. Proteomics. 2009 Mar;9(5):1326-43. PubMed, CrossRef
  38. Wang Z, Gerstein M, Snyder M. RNA-Seq: a revolutionary tool for transcriptomics. Nat Rev Genet. 2009 Jan;10(1):57-63. Review. PubMed, PubMedCentral, CrossRef
  39. Taniguchi Y, Choi PJ, Li GW, Chen H, Babu M, Hearn J, Emili A, Xie XS. Quantifying E. coli proteome and transcriptome with single-molecule sensitivity in single cells. Science. 2010 Jul 30;329(5991):533-8. PubMed, PubMedCentral, CrossRef
  40. Schwanhäusser B, Busse D, Li N, Dittmar G, Schuchhardt J, Wolf J, Chen W, Selbach M. Global quantification of mammalian gene expression control. Nature. 2011 May 19;473(7347):337-42. PubMed, CrossRef
  41. Anderson NL, Anderson NG, Pearson TW, Borchers CH, Paulovich AG, Patterson SD, Gillette M, Aebersold R, Carr SA. A human proteome detection and quantitation project. Mol Cell Proteomics. 2009 May;8(5):883-6. Review. PubMed, PubMedCentral, CrossRef
  42. Dandoy P, Meunier CF, Michiels C, Su BL. Hybrid shell engineering of animal cells for immune protections and regulation of drug delivery: towards the design of “artificial organs”. PLoS One. 2011;6(6):e20983. PubMed, PubMedCentral, CrossRef
  43. Zappacosta F, Huddleston MJ, Karcher RL, Gelfand VI, Carr SA, Annan RS. Improved sensitivity for phosphopeptide mapping using capillary column HPLC and microionspray mass spectrometry: comparative phosphorylation site mapping from gel-derived proteins. Anal Chem. 2002 Jul 1;74(13):3221-31. PubMed
  44. Marcos R, Monteiro RA, Rocha E. Design-based stereological estimation of hepatocyte number, by combining the smooth optical fractionator and immunocytochemistry with anti-carcinoembryonic antigen polyclonal antibodies. Liver Int. 2006 Feb;26(1):116-24. PubMed
  45. Shen Y, Kim J, Strittmatter EF, Jacobs JM, Camp DG 2nd, Fang R, Tolié N, Moore RJ, Smith RD. Characterization of the human blood plasma proteome. Proteomics. 2005 Oct;5(15):4034-45. PubMed
  46. Omenn GS, States DJ, Adamski M, Blackwell TW, Menon R, Hermjakob H, Apweiler R, Haab BB, Simpson RJ, Eddes JS, Kapp EA, Moritz RL, Chan DW, Rai AJ, Admon A, Aebersold R, Eng J, Hancock WS, Hefta SA, Meyer H, Paik YK, Yoo JS, Ping P, Pounds J, Adkins J, Qian X, Wang R, Wasinger V, Wu CY, Zhao X, Zeng R, Archakov A, Tsugita A, Beer I, Pandey A, Pisano M, Andrews P, Tammen H, Speicher DW, Hanash SM. Overview of the HUPO Plasma Proteome Project: results from the pilot phase with 35 collaborating laboratories and multiple analytical groups, generating a core dataset of 3020 proteins and a publicly-available database. Proteomics. 2005 Aug;5(13):3226-45. PubMed
  47. Hamacher M, Meyer HE. HUPO Brain Proteome Project: aims and needs in proteomics. Expert Rev Proteomics. 2005 Jan;2(1):1-3. Review. PubMed, CrossRef
  48. Migneault I, Hunter JM. Industrialized MS-based proteomics in the search for circulating biomarkers. Bioanalysis. 2009 Sep;1(6):1149-63. Review. PubMed, CrossRef
  49. Bibl M, Esselmann H, Otto M, Lewczuk P, Cepek L, Rüther E, Kornhuber J, Wiltfang J. Cerebrospinal fluid amyloid beta peptide patterns in Alzheimer’s disease patients and nondemented controls depend on sample pretreatment: indication of carrier-mediated epitope masking of amyloid beta peptides. Electrophoresis. 2004 Sep;25(17):2912-8. PubMed
  50. Espina V, Mueller C. Reduction of preanalytical variability in specimen procurement for molecular profiling. Methods Mol Biol. 2012;823:49-57. PubMed, CrossRef

Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License.