Abstract

Purpose: To identify and characterize at least one protein from each of the 20,300 human protein-coding genes. See Legrain et al., Mol. Cell Proteomics (2011). To facilitate disease-related biomarker development. Methods: Global collaborative Human Proteome Project (HPP), organized by the Human Proteome Organization (HUPO). Use of ProteomeXchange, linking data repositories EBI-PRIDE and neXtprot, file sharing system Tranche, mass spectrometry-based Peptide Atlas and SRM Atlas, and Ab-based Human Protein Atlas, to share data, reanalyze mass spectrometry findings with a rigorous, standardized protocol, and lay the foundation for protein biomarkers of health and disease. Results: The Human Proteome Project was announced at the HUPO World Congress in Sydney, Australia, in September 2010 and launched at the HUPO World Congress in Geneva, Switzerland, in September 2011. The HPP draws upon resource pillars for mass spectrometry, protein capture, and knowledge base. There is some degree of evidence at the protein level for about 13,000 of the 20,300 proteins. The HPP has two large collaborative components: the chromosome-centric C-HPP, with so far 16 national or international research teams characterizing the proteins coded by genes on one chromosome each; and the biology and disease-driven B/D-HPP, which has embraced the pre-existing organ-based and biofluid-based proteome projects of the past decade under the aegis of HUPO. For example, the chromosome 17 team is annotating the 1182 proteins coded by genes on this chromosome (based on Ensembl, SwissProt, and neXtprot), with a disease focus on breast cancer, reflecting the breast cancer-associated Chr 17 genes ERBB2 (Her2), BRCA1, p53, and GRB7. We are determining the concordance of protein identifications by immunohistochemistry and by mass spectrometry and the tissue expression patterns for the canonical proteins and for splice variants and various types of post-translational modifications. Information about the HPP is available at http://thehpp.org. Conclusions: The combined chromosome-centric and biology and disease-driven Human Proteome Project efforts are becoming well-organized. The HPP will add greatly to our confident identification of human proteins currently not yet identified or mapped for tissue and subcellular expression. The HPP provides a foundation for interpreting results of proteomic biomarker studies of osteoarthritis and integrating proteomics data with other omics platforms to relate genotype to phenotype (Figure 1).

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