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Chromosome-Centric Human Proteome Project  (C-HPP)

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

Participants (click on flags for more information)

 Chromosome teams
 Chromosome 1: Ping Xu - China Chromosome 14: Charles Pineau - France  
 Chromosome 2: Lydie Lane -Switzerland Chromosome 15: Gilberto Domont - Brazil  
 Chromosome 3: Takeshi Kawamura - Japan Chromosome 16: Fernando Corrales - Spain  
 Chromosome 4: Yu Ju Chen - Taiwan Chromosome 17: Gilbert S. Omenn - USA  
 Chromosome 5: Peter Horvatovitch - The Netherlands Chromosome 18: Alexander Archakov - Russia  
 Chromosome 6: Rob Moritz - USA/Canada Chromosome 19: Sergio Encarnacion - Mexico  
 Chromosome 7: Edouard Nice - Australia Chromosome 20: Siqi Liu - China 
 Chromosome 8: Gong Zhang - China Chromosome 21: Ulrich auf dem Keller - Denmark  
 Chromosome 9: Je-Yoel Cho - Korea Chromosome 22: Oded Kleifeld - Israel 
 Chromosome 10: Josh Labaer - USA Chromosome X: Yasushi Ishihama - Japan 
 Chromosome 11: Bong-Hee Lee - Korea Chromosome Y: Ghasem Hosseini Salekdeh - Iran
 Chromosome 12: Ravi Siredeshmukh - India Chromosome Mitochondrial: Andrea Urbani - Italy 
 Chromosome 13: Young-Ki Paik - Korea


2022 C-HPP Executive Committee (EC)

Chair: Christopher M. Overall, Canada (to December 31, 2024)
Co-Chair: Lydie Lane, Switzerland (to December 31, 2023)
Secretary General: Peter Horvatovich, The Netherlands (to December 31, 2022)
Member-at-Large: Gong Zhang, China (to December 31, 2024)
Member-at-Large: Fernando Corrales, Spain (to December 31, 2022)
Member-at-Large: Gilberto Domont, Brazil (to December 31, 2024)

C-HPP Meetings

The Chromosome Centric Human Proteome Project (C-HPP) announces the 25th C-HPP Workshop on “Accelerating the HPP Grand Challenge” to be held in Algarve, Portugal on Friday, May 13, 2022 following the 2nd Joint Meeting of Spanish, French, and Portuguese Proteomics Societies.

neXt-CP50 Reports

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. Overall, C.M. 2020. The HUPO High-stringency Inventory of Humanities Shared Human Proteome Revealed. Journal of Proteome Research 19, 4,211 – 4,214, doi/10.1021/acs.jproteome.0c00794.
  2. Overall, C.M. 2020. The Human Proteome: 90% in the Light — 10% on the Dark Side. Journal of Proteome Research 19, 4,731 – 4,735.
  3. Omenn, G.S., Lane, L., Overall, C.M., Cristea, I., Corrales, F., Lindskog, C., Paik, Y-K., Van Eyk, J., Liu, S., Snyder, M., Baker, M., Bandeira, N., Aebersold, R., Moritz, R., Deutsch, E. 2020. Research on The Human Proteome Reaches a Major Milestone: >90% of Predicted Human Proteins Now Credibly Detected, according to the HUPO Human Proteome Project. Journal of Proteome Research 19, 4,735 – 4,746. doi/10.1021/acs.jproteome.0c00485.
  4. 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.
  5. 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
  6. 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
  7. 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
  8. 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.

  9. 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

  10. 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

  11. 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
  12. 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
  13. 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
  14. 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
  15. 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
  16. 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

  17. 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 

  18. 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

  19. 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

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

  21. 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

  22. 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

  23. 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

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