{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:05:43Z","timestamp":1790712343872,"version":"4.1.0"},"reference-count":59,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82404370"],"award-info":[{"award-number":["82404370"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82101264"],"award-info":[{"award-number":["82101264"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["GZC20230130"],"award-info":[{"award-number":["GZC20230130"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2025T180210"],"award-info":[{"award-number":["2025T180210"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2024M750139"],"award-info":[{"award-number":["2024M750139"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Young Elite Scientists Sponsorship Program of the Beijing High Innovation Plan","award":["20250691"],"award-info":[{"award-number":["20250691"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>Psoriasis is a chronic, immune-mediated disorder with an unmet need for effective treatments. To systematically prioritize therapeutic targets, we integrated proteome-wide Mendelian randomization (MR) with expression validation in blood\/skin, genetic susceptibility analysis, differential gene expression (DGE) from bulk and single-cell RNA sequencing (scRNA-seq), colocalization, pathway enrichment, and protein-protein interaction analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Proteome-wide MR identified 29 candidate protein targets (Bonferroni-corrected), all replicated in independent datasets. Fifteen targets showed significant expression associations in blood or skin. Eleven proteins\u2014UBLCP1, IL23A, ASF1A, RARRES2, ICAM1, PRSS53, ICAM5, GCA, IL2RA, DBI, and NFKB1\u2014exhibited consistent directional effects with their genes. Genetic susceptibility analysis confirmed 20 target-specific polygenic scores for psoriasis and five for psoriatic arthritis. DGE analysis identified 13 targets in bulk and 13 in scRNA-seq\u2014primarily in keratinocytes and immune cells\u2014with IL2RA, COMP, and A2ML1 dysregulated across both. Colocalization analysis implicated shared causal variants for psoriasis in ASF1A, CD8A, CTF1, IL7R, MMP12, RARRES2, XCL2, DBI, IL23A, IL2RA, SGSH, and TIMD4. Enrichment analyses highlighted involvement in cytotoxicity, immune regulation, and JAK-STAT signaling. Eighteen targets interacted with approved anti-psoriasis drugs. Notably, drugs targeting IL2RA, IL7R, CTF1, ICAM1, MMP12, NFKB1, CD8A, DDX58, IL12A, SGSH, and FAP are approved or in trials for other diseases, suggesting repurposing potential. Our integrative multi-omics approach prioritized 29 high-confidence targets, including 13 novel candidates (RARRES2, ASF1A, CTF1, DBI, B3GNT2, CD8A, TIMD4, CRTAM, SGSH, XCL2, DAPK2, A2ML1, and FAP). Several high-priority targets\u2014such as IL2RA, IL23, MMP12, RARRES2, IL7R, and ICAM1\u2014were supported across analytical layers. These findings provide a robust foundation for psoriasis drug development.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>The code used for the analyses in this manuscript has been archived in Zenodo at [DOI: 10.5281\/zenodo.19692128].<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btag347","type":"journal-article","created":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T11:41:27Z","timestamp":1779882087000},"source":"Crossref","is-referenced-by-count":1,"title":["Integrated multi-omics strategies for identifying novel therapies in psoriasis"],"prefix":"10.1093","volume":"42","author":[{"given":"Shucheng","family":"Si","sequence":"first","affiliation":[{"name":"Research Center of Clinical Epidemiology, Peking University Third Hospital , Beijing, 100191,","place":["China"]},{"name":"Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education , Beijing, 100191,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6758-0685","authenticated-orcid":false,"given":"Xiaoxiao","family":"Wang","sequence":"additional","affiliation":[{"name":"Research Center of Clinical Epidemiology, Peking University Third Hospital , Beijing, 100191,","place":["China"]},{"name":"Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education , Beijing, 100191,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1654-3678","authenticated-orcid":false,"given":"Siyan","family":"Zhan","sequence":"additional","affiliation":[{"name":"Research Center of Clinical Epidemiology, Peking University Third Hospital , Beijing, 100191,","place":["China"]},{"name":"Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education , Beijing, 100191,","place":["China"]},{"name":"Department of Epidemiology and Biostatistics, School of Public Health, Peking University , Beijing, 100191,","place":["China"]},{"name":"Institute for Artificial Intelligence, Peking University , Beijing, 100191,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,5,28]]},"reference":[{"key":"2026062409125309500_btag347-B1","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1084\/jem.20080129","article-title":"Chemerin expression marks early psoriatic skin lesions and correlates with plasmacytoid dendritic cell recruitment","volume":"206","author":"Albanesi","year":"2009","journal-title":"J Exp Med"},{"key":"2026062409125309500_btag347-B2","doi-asserted-by":"crossref","first-page":"2377","DOI":"10.1007\/s10787-025-01758-2","article-title":"Systematic review of comparative studies on emerging psoriasis treatments: comparing biologics with biologics, small molecule 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