The 2024 Report on the Human Proteome from the HUPO Human Proteome Project

Abstract

The Human Proteome Project (HPP), the flagship initiative of the Human Proteome Organization (HUPO), has pursued two goals: (1) to credibly identify at least one isoform of every protein-coding gene and (2) to make proteomics an integral part of multiomics studies of human health and disease. The past year has seen major transitions for the HPP. neXtProt was retired as the official HPP knowledge base, UniProtKB became the reference proteome knowledge base, and Ensembl-GENCODE provides the reference protein target list. A function evidence FE1-5 scoring system has been developed for functional annotation of proteins, parallel to the PE1-5 UniProtKB/neXtProt scheme for evidence of protein expression. This report includes updates from neXtProt (version 2023-09) and UniProtKB release 2024_04, with protein expression detected (PE1) for 18138 of the 19411 GENCODE protein-coding genes (93%). The number of non-PE1 proteins ("missing proteins") is now 1273. The transition to GENCODE is a net reduction of 367 proteins (19,411 PE1-5 instead of 19,778 PE1-4 last year in neXtProt). We include reports from the Biology and Disease-driven HPP, the Human Protein Atlas, and the HPP Grand Challenge Project. We expect the new Functional Evidence FE1-5 scheme to energize the Grand Challenge Project for functional annotation of human proteins throughout the global proteomics community, including π-HuB in China.

Keywords: Biology and Disease-HPP (B/D-HPP); Chromosome-centric HPP (C-HPP); GENCODE; Grand Challenge Project; Human Protein Atlas; Human Proteome Organization (HUPO); Human Proteome Project (HPP); PeptideAtlas; function evidence (FE) scores; missing proteins (MP); neXtProt protein existence (PE) metrics; non-MS PE1 proteins; π-HuB (Protein Navigator).

Figure 1.

Summary of the larger recognizable groups of entries within the 1254 neXtProt entries that have been discarded because they are not found in the GENCODE protein-coding gene list. The PE level proportions vary widely among the groups, with “IgVar” entries being nearly all PE1 and “Putative” entries nearly all PE5.

Figure 2.

Summary of progress in identifying PE1 proteins via MS evidence (blue), proteins via other technologies besides MS (orange), and the missing proteins (gray) with no experimental evidence.

Figure 3.

Overview of the top five datasets contributing the most newly identified missing proteins out of 214 datasets added to PeptideAtlas in 2023. All other 209 datasets contributed three or fewer new previously-missing proteins.