Table 1 further documents the reduction of PE2,3,4 “missing proteins”, classified based on detectable levels of transcripts in human specimens (PE2), homologous protein expression in other species (PE3), or gene models predicted to be translated (PE4), from 5511 in 2012–02 to 1343 in 2022–02, a reduction of 78 in the past year, and now representing just 6.8% of the PE1,2,3,4 total of 19,750 predicted human proteins. These proteins constitute the main gene-based translation products, but the total number of protein species, including sequence variants, splice variants, and post-translationally modified proteoforms, is a substantial multiple of that figure. The total represents 93.2% of the 19,750 PE1,2,3,4 predicted proteins from protein-coding genes. Table 1 shows the annual progress in identifying proteins with credible protein-level evidence (PE1) from 13,975 proteins in 2012–02 to 18,407 PE1 proteins in the neXtProt release of 2022–02.

The human proteome database neXtProt curates and documents the proteins identified or predicted in a chromosome-specific manner for ease of organization 7. This work is supported by advances in developing data formats and standards by the HUPO Proteomics Standards Initiative (HUPO-PSI) 6 and the concomitant growth of PRIDE, PeptideAtlas, and other data repositories. The HPP is organized into 25 teams by chromosome and mitochondria, 19 teams by biological and disease categories, and four resource pillars for antibody-based protein localization, mass spectrometry, knowledgebases, and pathology. Through international collaboration, data sharing, standardized reanalysis of datasets, and guidelines for quality assurance, the HPP consortium has stimulated progress in building and utilizing proteomics knowledge globally. Since 2010, the Human Proteome Project (HPP) 1, the flagship initiative of the global Human Proteome Organization (HUPO) 2, has pursued two goals: (1) to credibly identify the protein “parts list”, primarily but not entirely by mass spectrometry, and (2) to make proteomics an integral part of multi-omics studies of human health and disease 3– 5. PROGRESS ON THE HUMAN PROTEOME PARTS LIST We present highlights from the Chromosome-Centric HPP, Biology and Disease-driven HPP, and HPP Resource Pillars, compare features of mass spectrometry and Olink and Somalogic platforms, note the emergence of translation products from ribosome profiling of small open reading frames, and discuss the launch of the initial HPP Grand Challenge Project, “A Function for Each Protein”. Meanwhile, applying proteomics in a vast array of biological and clinical studies continues to yield significant findings and growing integration with other omics platforms.

This represents continuing experimental progress on the proteome parts list across all the chromosomes, as well as significant reclassifications. Conversely, the number of neXtProt PE2, PE3, and PE4 missing proteins has been reduced by 78 from 1421 to 1343.

The 2022 Metrics of the Human Proteome from the HUPO Human Proteome Project (HPP) illustrates that protein expression has now been credibly detected (neXtProt PE1 level) for 18,407 (93.2%) of the 19,750 predicted proteins coded in the human genome, a net gain of 50 since 2021 from datasets generated around the world and reanalyzed by the HPP.

Simon pegg 2020