Plasma Proteomics, The Human Proteome Project, and Cancer-Associated Alternative Splice Variant Proteins

• Published in: Biochimica et biophysica acta Vol. 1844; no. 5; pp. 866 - 873
• Main Author: Omenn, Gilbert S.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.05.2014
• Subjects: alternative splicing; Alternative Splicing - genetics; antibodies; Biomarker; biomarkers; Biomarkers, Tumor - blood; Biomarkers, Tumor - genetics; Blood Proteins - classification; Blood Proteins - genetics; Blood Proteins - metabolism; Chromosomes, Human - genetics; Chromosomes, Human - metabolism; gene expression; genes; Human Genome Project; Human Plasma Peptide Atlas; Human Proteome Peptide Atlas; Human Proteome Project; Humans; mass spectrometry; neoplasms; Neoplasms - blood; Neoplasms - diagnosis; Neoplasms - genetics; pathogenesis; peptides; planning; Protein Isoforms; proteins; proteome; Proteome - analysis; proteomics; Proteomics - methods; Splice variant protein; Splice variant transcript; Biomarker; Human Proteome Project; Splice variant protein; Human Plasma Peptide Atlas; Human Proteome Peptide Atlas; Splice variant transcript
• ISSN: 1570-9639; 0006-3002; 1878-1454
• DOI: 10.1016/j.bbapap.2013.10.016

This article addresses three inter-related subjects: the development of the Human Plasma Proteome Peptide Atlas, the launch of the Human Proteome Project, and the emergence of alternative splice variant transcripts and proteins as important features of evolution and pathogenesis. The current Plasma Peptide Atlas provides evidence on which peptides have been detected for every protein confidently identified in plasma; there are links to their spectra and their estimated abundance, facilitating the planning of targeted proteomics for biomarker studies. The Human Proteome Project (HPP) combines a chromosome-centric C-HPP with a biology and disease-driven B/D-HPP, upon a foundation of mass spectrometry, antibody, and knowledgebase resource pillars. The HPP aims to identify the approximately 7000 “missing proteins” and to characterize all proteins and their many isoforms. Success will enable the larger research community to utilize newly-available peptides, spectra, informative MS transitions, and databases for targeted analyses of priority proteins for each organ and disease. Among the isoforms of proteins, splice variants have the special feature of greatly enlarging protein diversity without enlarging the genome; evidence is accumulating of striking differential expression of splice variants in cancers. In this era of RNA-sequencing and advanced mass spectrometry, it is no longer sufficient to speak simply of increased or decreased expression of genes or proteins without carefully examining the splice variants in the protein mixture produced from each multi-exon gene. This article is part of a Special Issue entitled: Biomarkers: A Proteomic Challenge. •Human Proteome Project has chromosome-centric and biology-and-disease-driven teams.•The HPP aims to identify approximately 7000 “missing proteins”.•HPP will enable life sciences community to utilize proteomics technologies and data.•Alternative splicing is a major source of protein diversity and complexity.•Differentially expressed cancer splice variants are clues to pathways and therapies.