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Early detection in ophthalmology clinics and timely intervention of cardiovascular complications can be lifesaving. In this study, a modified proteomics workflow with liquid chromatography\u2010tandem mass spectrometry (LC\u2010MS\/MS)\u2010based data\u2010independent acquisition (DIA) and field asymmetric ion mobility spectrometry (FAIMS) to profile the proteomes of aqueous humor (AH) and lens tissue from MFS children with ectopia lentis is utilized. Over 2300 and 2938 comparable proteins are identified in AH and the lens capsule, respectively. Functional enrichment analyses uncovered dysregulation of complement and coagulation\u2010related pathways, collagen binding, and cell adhesion in MFS. Through weighted correlation network analysis (WGCNA) and machine learning, distinct modules associated with clinical traits are constructed and a unique biomarker panel (Q14376, Q99972, P02760, Q07507; gene names: GALE, MYOC, AMBP, DPT) is defined. These biomarkers are further validated using advanced parallel reaction monitoring (PRM) in an independent patient cohort. The results provide novel insights into the proteome characterization of ectopia lentis and offer a promising approach for developing a valuable biomarker panel to aid in the early diagnosis of Marfan syndrome via AH proteome.<\/jats:p>","DOI":"10.1002\/advs.202303161","type":"journal-article","created":{"date-parts":[[2023,12,13]],"date-time":"2023-12-13T08:59:00Z","timestamp":1702457940000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Uncovering the Hidden World of Aqueous Humor Proteins for Discovery of Biomarkers for Marfan Syndrome"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9612-8989","authenticated-orcid":false,"given":"Yumeng","family":"Shi","sequence":"first","affiliation":[{"name":"Eye Institute and Department of Ophthalmology, Eye and ENT Hospital Fudan University  Shanghai 200031 China"},{"name":"NHC Key Laboratory of Myopia Fudan University  Shanghai 200031 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