Advances in Identifying and Characterizing the Human Proteome

On the basis of the January 2019 updates on the curation and annotation of the human proteome by neXtProt4 (https://www.nextprot.org/) from the standardized reanalysis of mass spectrometry (MS) data sets by PeptideAtlas5 (http://www. peptideatlas.org/), which form the baseline for the 2019 papers in this special issue, Omenn et al. (10.1021/acs.jproteome.9b00434) report that highly credible findings supportProtein Evidence Level 1 (PE1) for 17 694 protein-coding genes, 89.3% of the total 19 823 predicted human proteincoding genes. In this annual metric of the human proteome paper, these numbers represent a net increase of 224 PE1 proteins due to the promotion of 213 PE2,3,4 entries to PE1 and a net decrease of only 57 missing proteins (MPs) due to 60 PE1 demotions and 116 new PE2,3,4 entries, primarily immunoglobulins. The dynamics of the year-to-year changes in neXtProt are quite complex, as explained in this article. A chromosome-bychromosome analysis showed that four chromosomes (1, 5, 17, 19) have had reductions of between 50 and 130 MPs, and another four (2, 3, 10, X) have had 43−47 fewer MPs since the baseline for the neXt-MP50 Challenge in 2016. Utilizing ProteomeXchange, PRIDE, and other data resources, PeptideAtlas documented an increase of 495 canonical proteins from 120 new human sample data sets; three data sets from the JPR 2018 special issue contributed a major proportion of these with 161 of the 495. The canonical proteins from PeptideAtlas account for 98% of the 16 600 PE1 neXtProt entries based on MS, compliant with the stringent HPP Guidelines v2.1.6 More than half of the new canonical proteins were already PE1 but were based on other kinds of non-mass-spectrometry protein evidenceThis work was supported by grants from the Korean Ministry of Health and Welfare (HI13C2098 International Consortium Project and HI16C0257 to Y.-K.P.), the Canadian Institutes of Health Research, 7-year Foundation Grant [FDN148408], and a Canada Research Chair in Protease Proteomics and Systems Biology (awarded to C.M.O), the U.S. National Institutes of Health (P30ES017885-01A1 and U24CA210967 to G.S.O.), and ProteoRed and PRB3-ISCIII PT17/0019 (Spanish Institutes of Health ISCIII to F.C.)