{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T02:53:37Z","timestamp":1790391217104,"version":"4.1.0"},"reference-count":93,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2020,9,2]],"date-time":"2020-09-02T00:00:00Z","timestamp":1599004800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2018YFA0507504"],"award-info":[{"award-number":["2018YFA0507504"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["61773025"],"award-info":[{"award-number":["61773025"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,5,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Phase separation is an important mechanism that mediates the spatial distribution of proteins in different cellular compartments. While phase-separated proteins share certain sequence characteristics, including intrinsically disordered regions (IDRs) and prion-like domains, such characteristics are insufficient for making accurate predictions; thus, a proteome-wide understanding of phase separation is currently lacking. Here, we define phase-separated proteomes based on the systematic analysis of immunofluorescence images of 12\u00a0073 proteins in the Human Protein Atlas. The analysis of these proteins reveals that phase-separated candidate proteins exhibit higher IDR contents, higher mean net charge and lower hydropathy and prefer to bind to RNA. Kinases and transcription factors are also enriched among these candidate proteins. Strikingly, both phase-separated kinases and phase-separated transcription factors display significantly reduced substrate specificity. Our work provides the first global view of the phase-separated proteome and suggests that the spatial proximity resulting from phase separation reduces the requirement for motif specificity and expands the repertoire of substrates. The source code and data are available at https:\/\/github.com\/cheneyyu\/deepphase.<\/jats:p>","DOI":"10.1093\/bib\/bbaa187","type":"journal-article","created":{"date-parts":[[2020,7,22]],"date-time":"2020-07-22T15:16:40Z","timestamp":1595431000000},"source":"Crossref","is-referenced-by-count":20,"title":["Proteome-scale analysis of phase-separated proteins in immunofluorescence images"],"prefix":"10.1093","volume":"22","author":[{"given":"Chunyu","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Biomedical Informatics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boyan","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaiqiang","family":"You","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minglei","family":"Shi","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory of Bioinformatics; Bioinformatics Division and Center for Synthetic & Systems Biology, TNLIST; School of Medicine, Tsinghua University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Congying","family":"Wu","sequence":"additional","affiliation":[{"name":"Institute of Systems 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Acids Res"},{"key":"2021052110412348600_ref46","first-page":"855","author":"Grover","year":"2016"},{"key":"2021052110412348600_ref47","first-page":"2579","article-title":"Visualizing data using t-SNE","volume":"9","author":"Lvd","year":"2008","journal-title":"J Mach Learn Res"},{"key":"2021052110412348600_ref48","doi-asserted-by":"crossref","DOI":"10.15252\/embj.2018101379","article-title":"Phase separation of 53BP1 determines liquid-like behavior of DNA repair compartments","volume":"38","author":"Kilic","year":"2019","journal-title":"EMBO J"},{"key":"2021052110412348600_ref49","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1017\/S1431927612014353","article-title":"Hybrid detectors improved time-lapse confocal microscopy of PML and 53BP1 nuclear body colocalization in DNA lesions","volume":"19","author":"Foltankova","year":"2013","journal-title":"Microsc Microanal"},{"key":"2021052110412348600_ref50","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms7533","article-title":"Cmr1\/WDR76 defines a nuclear genotoxic stress body linking genome integrity and protein quality control","volume":"6","author":"Gallina","year":"2015","journal-title":"Nat Commun"},{"key":"2021052110412348600_ref51","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.molcel.2017.03.014","article-title":"A compendium of RNA-binding proteins that regulate microRNA biogenesis","volume":"66","author":"Treiber","year":"2017","journal-title":"Mol Cell"},{"key":"2021052110412348600_ref52","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1261\/rna.063719.117","article-title":"Dissecting the functions of SMG5, SMG7, and PNRC2 in nonsense-mediated mRNA decay of human 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