Chromosome 6

1.1. Group composition

Participating country(ies): USA\Canada\Qatar
Head: Robert Moritz - Institute for Systems Biology, USA
Co-Lead:Christopher Overall - U. British Columbia, Canada
Member:Frank Schmidt - Weill-Cornell, Qatar
Member:John Wilson - Protifi, USA
Member:Eric Deutsch - Institute for Systems Biology, USA

1.2. Missing proteins

Protein evidence according to NeXtProt for Chromosome 6:
Protein evidence status in text format is available here.

1.3. Bioinformatics protocols

1.4. Analytical protocols

1.5. Biological projects

1.6. Biomaterials

1.7. Data sets

1.8. Special expertise

The exact position and N-terminal chemistry of a protein chain often define the biological activity of a protein. The Chris Overall group, UBC has unique expertise in defining the N (and C-termini) of proteins by proteomics. By analysis of common and rare human tissues the Overall Lab is annotating the N-termini of proteins of Chromosome 6 and other chromosomes for the HPP. Thus we are identifying:

• Co-translational derived mature original N-terminus
• Post-translational cleavage derived stable cleavage chains
• Annotation of +/- Met, site of signal peptide removal, zymogen activation
• +/- Acetylation, other modifications
• Alternate start sites
• Archetypical N-terminal peptides
• SRMs to quantify amounts of cleaved vs. uncleaved
• Neo-epitope antibodies to biologically important protein chains directed to the N or C termini after cleavage

For harsh sample solubilization, we are employing methods with high detergent concentration (e.g., SDS) and a processing method that will clear the protein lysate of detergents and digest the proteins in situ (STraps). Our unique expertise (Protifi) in sample treatment is being developed to tackle heavily membrane bound proteins that are frequently missing from proteome analysis results.

For rare sample and targeted human tissue access, our Qatar based group headed by Frank Schmidt has a repository of human tissue that is being used to extensively mine with the methods developed within the Ch6 team

1.9. Major achievements

A review of the chromosome 6 project has been published, link
Borchers et al., 'The Human Proteome Organization Chromosome 6 Consortium: Integrating chromosome-centric and biology/disease driven strategies', Journal of Proteomics 100 (2014), 60-67.

Rare tissue analysis:

• Prudova, A., Serrano, K., Eckhard, U., Fortelny, N., Devine, D. V., Overall, C. M., TAILS N-terminomics of human platelets reveals pervasive metalloproteinase-dependent proteolytic processing in storage, e-Blood, 2014, 124(26):e49-e60.
• Lange, P.F., Huesgen, P.F., Nguyen, K., Overall, C. M., Annotating N Termini for the Human Proteome Project: N Termini and Nα-Acetylation Status Differentiate Stable Cleaved Protein Species from Degradation Remnants in the Human Erythrocyte Proteome, Journal of Proteome Research, 2014, 13, 2028−2044.
• Eckhard, U., Marino, G., Abbey, S. R., Tharmarajah, G., Matthew, I., Overall, C. M., The Human Dental Pulp Proteome and N‑Terminome: Levering the Unexplored Potential of Semitryptic Peptides Enriched by TAILS to Identify Missing Proteins in the Human Proteome Project in Underexplored Tissues, Journal of Proteome Research, 2015, 14, 3568−3582.
• Eckhard, U., Marino, G., Abbey, S. R., Matthew, I., Overall, C. M., TAILSN-terminomic and proteomic datasets of healthy human dental pulp, Data in Brief, 2015, 5, 542–548.
• Abbey, S. R., Eckhard, U., Solis, N., Marino, G., Matthew, I., Overall, C. M., The Human Odontoblast Cell Layer and Dental Pulp Proteomes and N-Terminomes, Journal of Dental Research, 2017.

Database search tool

• Lange, P. F., Huesgen, P. F., Overall, C. M., TopFIND 2.0 - linking protein termini with proteolytic processing and modifications altering protein function, Nucleic Acids Research, 2012, 40, D351–D361.
• Lange, P. F., Overall, C. M., TopFIND, a knowledgebase linking protein termini with function, Nature Methods, 2011, 8, pages 703–704.

Other papers:

• Overall, C. M., Can proteomics fill the gap between genomics and phenotypes? Journal of Proteomics, 2014, 100, 1-2.
• Borchers, C.H., Kast, J., Foster, L.J., Siud, K.W.M., Overall, C.M., Binkowski, T.A., Hildebrand, W.H., Scherer, A., Mansoor, M., Keown, P.A., for the Human Proteome Organization Chromosome 6 Consortium, The Human Proteome Organization Chromosome 6 Consortium: Integrating chromosome-centric and biology/disease driven strategies, Journal of Proteomics, 2014, 100, 60-67.
• Huesgen, P. F., Lange, P. F., Rogers, L. D., Solis, N., Eckhard, U., Kleifeld, O., Goulas, T., Gomis-Rüth, F. X., Overall, C.M., LysargiNase mirrors trypsin for protein C-terminal and methylation-site identification, Nature Methods, 2015, 12(1):55-58.
• Paik, Y.K., Omenn, G. S., Overall, C.M., Deutsch, E., W., Hancock, W. S., Recent Advances in the Chromosome-Centric Human Proteome Project: Missing Proteins in the Spot Light, Journal of Proteome Research, 2015, 14, 3409−3414.
• Marino, G., Eckhard, U., Overall, C. M., Protein Termini and Their Modifications Revealed by Positional Proteomics, Chemical Biology, 2015, 10(8):1754-1764.
• Eckhard U., Marino, G., Butler, G. S., Overall, C. M., Positional proteomics in the era of the human proteome project on the doorstep of precision medicine, Biochimie 2016, 122, 110e118.
• Deutsch, E.W., Overall, C.M., Van Eyk, J.E., Baker, M.S., Paik, Y.K., Weintraub, S.T., Lane, L., Martens, L., Vandenbrouck, Y., Kusebauch, U., Hancock, W.S., Hermjakob, H., Aebersold, R, Moritz R.L., Omenn, G. S., Human Proteome Project Mass Spectrometry Data Interpretation Guidelines 2.1., J Proteome Res., 2016, 15(11):3961-3970.
• Omenn, G.S., Lane, L., Lundberg, E.K., Beavis, R.C., Overall, C.M., Deutsch, E.W., Metrics for the Human Proteome Project 2016: Progress on Identifying and Characterizing the Human Proteome, Including Post-Translational Modifications, J Proteome Res., 2016, 15(11):3951-3960.
• Paik, Y.K., Overall, C.M., Deutsch, E.W., Hancock, W.S., Omenn, G.S., Progress in the Chromosome-Centric Human Proteome Project as Highlighted in the Annual Special Issue IV, J Proteome Res. 2016, 15(11):3945-3950.
• 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, 2017, 14(12):1059-1071.
• Klein, T., Eckhard, U., Dufour, A., Solis, N., Overall, C.M., Proteolytic Cleavage-Mechanisms, Function, and "Omic" Approaches for a Near-Ubiquitous Posttranslational Modification, Chem Rev., 2018, 118(3):1137-1168.
• Paik YK, Lane L, Kawamura T, Chen YJ, Cho JY, LaBaer J, Yoo JS, Domont G, Corrales F, Omenn GS, Archakov A, Encarnación-Guevara S, Lui S, Salekdeh GH, Cho JY, Kim CY, Overall C.M., Launching the C-HPP neXt-CP50 Pilot Project for Functional Characterization of Identified Proteins with No Known Function, J Proteome Res. 2018 Dec 7;17(12):4042-4050.
• Omenn GS, Lane L, Overall CM, Corrales FJ, Schwenk JM, Paik YK, Van Eyk JE, Liu S, Pennington S, Snyder MP, Baker MS, Deutsch EW., Progress on Identifying and Characterizing the Human Proteome: 2018-2019 Metrics from the HUPO Human Proteome Project, J Proteome Res. 2019.

Human SRMAtlas: A Resource of Targeted Assays to Quantify the Complete Human Proteome.
Kusebauch U, Campbell DS, Deutsch EW, Chu CS, Spicer DA, Brusniak MY, Slagel J, Sun Z, Stevens J, Grimes B, Shteynberg D, Hoopmann MR, Blattmann P, Ratushny AV, Rinner O, Picotti P, Carapito C, Huang CY, Kapousouz M, Lam H, Tran T, Demir E, Aitchison JD, Sander C, Hood L, Aebersold R, Moritz RL. Cell. 2016 Jul 28;166(3):766-778. doi: 10.1016/j.cell.2016.06.041. Epub 2016 Jul 21. PMID: 27453469

1.10. The neXt-MP50 challenge