Metrics for the Human Proteome Project 2016: Progress on Identifying and Characterizing the Human Proteome, Including Post-Translational Modifications

Abstract

The HUPO Human Proteome Project (HPP) has two overall goals: (1) stepwise completion of the protein parts list—the draft human proteome including confidently identifying and characterizing at least one protein product from each protein-coding gene, with increasing emphasis on sequence variants, post-translational modifications (PTMs), and splice isoforms of those proteins; and (2) making proteomics an integrated counterpart to genomics throughout the biomedical and life sciences community. PeptideAtlas and GPMDB reanalyze all major human mass spectrometry data sets available through ProteomeXchange with standardized protocols and stringent quality filters; neXtProt curates and integrates mass spectrometry and other findings to present the most up to date authorative compendium of the human proteome. The HPP Guidelines for Mass Spectrometry Data Interpretation version 2.1 were applied to manuscripts submitted for this 2016 C-HPP-led special issue [www.thehpp.org/guidelines]. The Human Proteome presented as neXtProt version 2016-02 has 16,518 confident protein identifications (Protein Existence [PE] Level 1), up from 13,664 at 2012-12, 15,646 at 2013-09, and 16,491 at 2014-10. There are 485 proteins that would have been PE1 under the Guidelines v1.0 from 2012 but now have insufficient evidence due to the agreed-upon more stringent Guidelines v2.0 to reduce false positives. neXtProt and PeptideAtlas now both require two non-nested, uniquely mapping (proteotypic) peptides of at least 9 aa in length. There are 2,949 missing proteins (PE2+3+4) as the baseline for submissions for this fourth annual C-HPP special issue of Journal of Proteome Research. PeptideAtlas has 14,629 canonical (plus 1187 uncertain and 1755 redundant) entries. GPMDB has 16,190 EC4 entries, and the Human Protein Atlas has 10,475 entries with supportive evidence. neXtProt, PeptideAtlas, and GPMDB are rich resources of information about post-translational modifications (PTMs), single amino acid variants (SAAVSs), and splice isoforms. Meanwhile, the Biology- and Disease-driven (B/D)-HPP has created comprehensive SRM resources, generated popular protein lists to guide targeted proteomics assays for specific diseases, and launched an Early Career Researchers initiative.

Advances in the Chromosome-Centric Human Proteome Project: looking to the future

“…The C-HPP teams have played a key role in setting some HPP milestones in six areas of cooperation with the bioinformatics teams and individual investigators. The areas of cooperation are: (i) the “Metrics” system for updating the yearly progress in protein annotation [13], (ii) the PXD data submission rule, which was a first step toward community-wide data sharing, (iii) the MS data interpretation guidelines v2.1 (the Guidelines v2.1) [14, 15], (iv) data managing bioinformatics tools, (v) collaboration for the JPR special issue publications, and (vi) rare sample utilization for MP detection. These accomplishments of the C-HPP would have been impossible without HUPO community-wide support and cooperation.…”

Progress in the Chromosome-Centric Human Proteome Project as Highlighted in the Annual Special Issue IV

“…The Chromosome 2 and Chromosome 14 teams of the C-HPP have exploited this approach admirably with their focus on testis and spermatozoa proteomes. Last year the Human Protein Atlas reported from transcriptome analyses that, among all of the tissues and organs of the body, testis has by far the largest number of tissue-specific transcripts (50×) or highly enriched transcripts (5×) more than any other tissue type, with an initial total of 999 predicted proteins, 11 adjusted this year to 879 as described by Omenn et al 5 in this Special Issue.…”

Highlights of the Biology and Disease-driven Human Proteome Project, 2015–2016

“…The HPP is a focal point for many proteomic research laboratories around the world and enhances the quality and interconnectedness of proteomics data resources (https://www.hupo.org/human-proteome-project/). 1–3 The HPP is composed of three resource pillars, the C-HPP (chromosome-centric) initiative and the Biology and Disease-driven B/D-HPP. The B/D-HPP aims to develop targeted and high-throughput proteomics analyses, address research challenges of biological and disease networks, and generate multiplex assays of proteins especially suited for particular cells, tissues, and organs in health and across many diseases (http://www.thehpp.org/BD-HPP.php)…”