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Target identification and validation are crucial for the discovery of protein and peptide drugs, and bioinformatics prediction of targets based on the characteristics of known target proteins will help improve the efficiency and success rate of target selection. However, owing to the developmental history in the pharmaceutical industry, previous systematic exploration of the target spaces has mainly focused on traditional small-molecule drugs, while studies related to protein and peptide drugs are lacking. Here, we systematically explore the target spaces in the human genome specifically for protein and peptide drugs. Compared with other proteins, both successful protein and peptide drug targets have many special characteristics, and are also significantly different from those of small-molecule drugs in many aspects. Based on these features, we develop separate effective genome-wide target prediction models for protein and peptide drugs. Finally, a user-friendly web server, Predictor Of Protein and PeptIde drugs\u2019 therapeutic Targets (POPPIT) (http:\/\/poppit.ncpsb.org.cn\/), is established, which provides not only target prediction specifically for protein and peptide drugs but also abundant annotations for predicted targets.<\/jats:p>","DOI":"10.1016\/j.gpb.2021.10.007","type":"journal-article","created":{"date-parts":[[2022,3,23]],"date-time":"2022-03-23T19:53:07Z","timestamp":1648065187000},"page":"780-794","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":3,"title":["Exploration of Target Spaces in the Human Genome for Protein and Peptide Drugs"],"prefix":"10.1093","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3371-2392","authenticated-orcid":false,"given":"Zhongyang","family":"Liu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics , Beijing, 102206 , China"},{"name":"School of Basic Medical Sciences, Anhui Medical University , Hefei, 230032 , China"},{"name":"College of Chemistry and Environmental Science, Hebei University , Baoding, 071002 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6085-0950","authenticated-orcid":false,"given":"Honglei","family":"Li","sequence":"additional","affiliation":[{"name":"Suzhou Geneworks Technology Co., Ltd. , Suzhou, 215028 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7945-4173","authenticated-orcid":false,"given":"Zhaoyu","family":"Jin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics , Beijing, 102206 , 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China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3546-429X","authenticated-orcid":false,"given":"Liying","family":"Yuan","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Hebei University , Baoding, 071002 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8571-2351","authenticated-orcid":false,"given":"Fuchu","family":"He","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics , Beijing, 102206 , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8680-0468","authenticated-orcid":false,"given":"Dong","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences 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