{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T12:59:44Z","timestamp":1790341184632,"version":"4.1.0"},"reference-count":52,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Proteomics Clinical Apps"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Systemic lupus erythematosus (SLE) is an autoimmune disease closely associated with enzyme dysfunction, yet its underlying molecular mechanisms remain incompletely understood. This study aims to characterize enzyme\u2010network alterations associated with SLE status and disease activity and to identify candidate molecules with potential clinical relevance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We integrated proteomic and phosphoproteomic data from peripheral blood mononuclear cells (PBMCs) of 130 SLE patients and 90 healthy controls (HC), along with transcriptomic data from 1461 SLE patients. Through systematic analysis of key enzyme phosphorylation sites, upstream transcription factors (TFs), and computationally prioritized candidate compounds, we sought to characterize enzyme\u2010centered regulatory associations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Integrated proteomic and phosphoproteomic analyses revealed significant metabolic and signaling pathway disturbances, along with distinct phosphorylation patterns in SLE immune cells. Multiple SLE\u2010associated and disease\u2010activity\u2010associated candidate molecules were identified. Regulatory network analysis uncovered an upstream transcription factor cluster centered around STAT1. Computational drug screening identified computationally prioritized candidate compounds with multi\u2010gene DSigDB associations, which require further clinical safety evaluation and experimental validation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study constructs a molecular map of SLE, highlighting associations between enzyme\u2010network alterations, catalytic dysregulation, and SLE\u2010related immune molecular signatures, and identifies candidate molecules for future clinical and functional evaluation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/prca.70056","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T07:30:41Z","timestamp":1789025441000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Multi\u2010Omics Landscape of Enzymatic Alterations in Systemic Lupus Erythematosus"],"prefix":"10.1002","volume":"20","author":[{"given":"Lingling","family":"Zhou","sequence":"first","affiliation":[{"name":"School of Medicine Anhui University of Science &amp; Technology  Huainan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5453-2547","authenticated-orcid":false,"given":"Qinxin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Peking University Shenzhen Hospital  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4375-0368","authenticated-orcid":false,"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Peking University Shenzhen Hospital  Shenzhen 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