Chromosome-Centric Human Proteome Project  (C-HPP)


The mission of the C-HPP

The Human Proteome Project (HPP) of the Human Proteome Organization (HUPO) aims to find high-stringency evidence for all proteins encoded by the human genome, the major splice forms of each protein, mature N- and C-termini, and their major protein post-translational modifications (PTMs). Indeed, one cannot do the best biology and/or medical research without a complete understanding of the parts of the human proteome. Conversely, the international C-HPP teams need the input of biology/disease (B/D) teams to understand the biological context of the parts list. It is a question of focus. A focus on the parts list promotes a measurement- and detail-focused analytical mindset, while a focus on the biological context is focused on outcomes and may ignore individual parts in the context of the overall picture. In conclusion, both mindsets are indivisible parts of the larger HPP initiative.

Questions and Answers on the C-HPP and Missing Proteins: Q & A


2019 C-HPP Executive Committee (EC)

Chair: Christopher M. Overall, Canada (to December 31, 2021)
Co-Chair: Lydie Lane, Switzerland (to December 31, 2020)
Co-Chair: Young-Ki Paik, Korea (to December 31, 2021)
Secretary General: Peter Horvatovich,The Netherlands (to December 31, 2019)
Member-at-Large: Pengyuan Yang, China (to December 31, 2021)
Member-at-Large: Fernando Corrales, Spain (to December 31, 2019)
Member-at-Large: Gilberto Domont, Brazil (to December 31, 2021)

C-HPP Annual Reports

neXt-CP50 Reports (a Dark Protein Initiative)

By analogy to the term “dark proteins” coined to represent structurally uncharacterized regions, C-HPP investigators have recently adopted the term “dark proteome” to collectively refer to those proteins for which we have insufficient

information on either protein expression, structure, function, or all of these: They include, for example, MPs (PE2−4), PE5, uPE1 proteins, and any potential proteins translated from smORF or lncRNAs. When focused on uPE1 proteins, there are nearly 2,000 proteins which have no functional information (Paik et al., 2018, JPR, DOI:10.1021/acs.jproteome.8b00383).

On March 1, 2018, HUPO C-HPP announced launching the neXt-CP50 where CP stands for “characterization of proteins”. This pilot project aims to characterize function of 50 uPE1 proteins during ~3 years (2018-2021). This challenge is to test the feasibility of the functional characterization of large numbers of dark proteins, 2000 at present the 15 teams are focusing on specific tractable targets that can be investigated

Of the C-HPP consortium international teams, 15 from 12 countries joined this project: Chr 2 (Switzerland), Chr 3 (Japan), Chr 4 (Taiwan), Chr 9, 11, 13 (Korea), Chr 10, Chr 14 (France), Chr 15 (Brazil), Chr 16 (Spain), Chr 17 (USA), Chr 18 (Russia), Chr 19 (Mexico), Chr 20 (China), and Chr Y (Iran).

C-HPP Papers

  1. Omenn, Gilbert;Lane, Lydie; Overall,Christopher;Corrales, Fernando;Schwenk, Jochen;Paik, Young-Ki; Van Eyk, Jennifer;Pennington, Stephen;Snyder, Michael; Baker, Mark; Deutsch, Eric. Progress on Identifying and Characterizing the Human Proteome: 2018-2019 Metrics from the HUPO Human Proteome Project.
  2. Jang, K. H., Yoon, H. N., Lee, J., Yi, H. et al., Liver disease-associated keratin 8 and 18 mutations modulate keratin acetylation and methylation. FASEB J. 33, 9030-9043 (2019).  PMID: 31199680
  3. Kopylov, A. T., Ponomarenko, E. A., Ilgisonis, E. V., Pyatnitskiy, M. A. et al., 200+ Protein Concentrations in Healthy Human Blood Plasma: Targeted Quantitative SRM SIS Screening of Chromosomes 18, 13, Y, and the Mitochondrial Chromosome Encoded Proteome. J. Proteome Res. 18, 120-129 (2019).  PMID: 30480452
  4. Paik, Y. K., Lane, L., Kawamura, T., Chen, Y. J. et al., Launching the C-HPP neXt-CP50 Pilot Project for Functional Characterization of Identified Proteins with No Known Function. J. Proteome Res. 17, 4042-4050 (2018).  PMID: 30269496
  5. Gilbert S. Omenn,Lydie Lane,Christopher M. Overall,Fernando J. Corrales, Jochen M. Schwenk, Young-Ki Paik, Jennifer E. Van Eyk, Siqi Liu, Michael Snyder, Mark S. Baker, and Eric W. Deutsch. J. Proteome Res. 2018, 17, 4031−4041 Progress on Identifying and Characterizing the Human Proteome: 2018 Metrics from the HUPO Human Proteome Project.

  6. Toward Completion of the Human Proteome Parts List: Progress Uncovering Proteins That Are Missing or Have Unknown Function and Developing Analytical Methods. J. Proteome Res. 2018, 17, 4023−4030

  7. Theo Klein, Ulrich Eckhard,Antoine Dufour,†Nestor Solis, and Christopher M. Overall. Proteolytic CleavageMechanisms, Function, and “Omic” Approaches for a Near-Ubiquitous Posttranslational Modification. Chem. Rev. 2018, 118, 1137−1168

  8. Nikolaus Fortelny, Christopher M. Overall, Paul Pavlidis & Gabriela V. Cohen Can we predict protein from mRNA levels? Nature 509, 582–587 (2014); doi:10.1038/nature13319: 27 July 2017 | VOL 547 | NATURE | e 1 9
  9. Paik, Y. K., Omenn, G. S., Hancock, W. S., Lane, L. & Overall, C. M., Advances in the Chromosome-Centric Human Proteome Project: looking to the future. Expert Rev Proteomics 14, 1059-1071 (2017).  PMID: 29039980
  10. Paik, Y. K., Overall, C. M., Deutsch, E. W., Van Eyk, J. E. & Omenn, G. S., Progress and Future Direction of Chromosome-Centric Human Proteome Project. J. Proteome Res. 16, 4253-4258 (2017).  PMID: 29191025
  11. Lee, J. Y., Lee, H. K., Park, G. W., Hwang, H. et al., Characterization of Site-Specific N-Glycopeptide Isoforms of α-1-Acid Glycoprotein from an Interlaboratory Study Using LC-MS/MS. J. Proteome Res. 15, 4146-4164 (2016).  PMID: 27760464
  12. Park, G. W., Hwang, H., Kim, K. H., Lee, J. Y. et al., Integrated Proteomic Pipeline Using Multiple Search Engines for a Proteogenomic Study with a Controlled Protein False Discovery Rate. J. Proteome Res. 15, 4082-4090 (2016).  PMID: 27537616
  13. Eric W. Deutsch,Christopher M. Overall,Jennifer E. Van Eyk, Mark S. Baker,Young-Ki Paik,Susan T. Weintraub,Lydie Lane,Lennart Martens,Yves Vandenbrouck,Ulrike Kusebauch, William S. Hancock, Henning Hermjakob, Ruedi Aebersold, Robert L. Moritz,and Gilbert S. Omenn. Human Proteome Project Mass Spectrometry Data Interpretation Guidelines 2.1. (2016) J. Proteome Res. 2016, 15, 3961−3970

  14. Gilbert S. Omenn, Lydie Lane, Emma K. Lundberg, Ronald C. Beavis, Christopher M. Overall, and Eric W. Deutsch. Metrics for the Human Proteome Project 2016: Progress on Identifying and Characterizing the Human Proteome, Including Post-Translational Modifications. J. Proteome Res. 2016, 15, 3951−3960 

  15. Cho, J. Y., Lee, H. J., Jeong, S. K., Kim, K. Y. et al., Combination of Multiple Spectral Libraries Improves the Current Search Methods Used to Identify Missing Proteins in the Chromosome-Centric Human Proteome Project. J. Proteome Res. 14, 4959-4966 (2015).  PMID: 26330117

  16. C.H. Borchers, J. Kast, L.J. Foster, K.W.M. Siu, C.M. Overall, T.A. Binkowski,W.H. Hildebrand, A. Scherer, M. Mansoor, P.A. Keowni. The Human Proteome Organization Chromosome 6 Consortium: Integrating chromosome-centric and biology/disease driven strategies Journal of Proteomics 100 (2014) 60 – 67

  17. Paik, Y. K. & Hancock, W. S., Uniting ENCODE with genome-wide proteomics. Nat. Biotechnol. 30, 1065-1067 (2012).  PMID: 23138303

  18. Paik, Y. K., Jeong, S. K., Omenn, G. S., Uhlen, M. et al., The Chromosome-Centric Human Proteome Project for cataloging proteins encoded in the genome. Nat. Biotechnol. 30, 221-223 (2012).  PMID: 22398612

  19. Na, K., Lee, M. J., Jeong, H. J., Kim, H. & Paik, Y. K., Differential gel-based proteomic approach for cancer biomarker discovery using human plasma. Methods Mol. Biol. 854, 223-237 (2012).  PMID: 22311764

  20. Legrain, P., Aebersold, R., Archakov, A., Bairoch, A. et al., The human proteome project: current state and future direction. Mol. Cell Proteomics 10, M111.009993 (2011).  PMID: 21742803

Participants


 Chr No. Leader Country
 Chr. 1 Ping Xu

China

 Chr. 2

Lydie Lane

Switzerland

 Chr. 3Takashi Kawamura

Japan

 Chr. 4

Yu Ju Chen

Taiwan

 Chr. 5 Peter Horvatovich Netherlands 
 Chr. 6

Robert Moritz

USA
 Chr. 7

Edouard Nice

Australia

 Chr. 8

Pengyuan Yang

China

 Chr. 9 Je-Yoel Cho Korea 
 Chr.10 Joshua Labaer USA
 Chr.11

Jong Shin Yoo

Korea

 Chr.12

Ravi Sirdeshmukh

India
 Chr.13

Young-Ki Paik

Korea
 Chr.14 Charles Pineau
France
 Chr.15 Gilberto B. Domont Brazil
 Chr.16

Fernando Corrales

Spain

 Chr.17

Gilbert S. Omenn

USA
 Chr.18

Alexander Archakov

Russia
 Chr.19Sergio Encarnación-GuevaraMexico
 Chr.20 Siqi Liu China 
 Chr.21

Albert Sickmann

Germany

 Chr.22 Akhileshi Pandey USA 
 Chr. X Yasushi Ishihama

Japan

 Chr. Y Ghasem Hosseini Salekdeh
Iran
 MitochondriaAndrea Urbani Italy




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