{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T13:34:38Z","timestamp":1785850478447,"version":"3.56.0"},"reference-count":117,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2024,9,25]],"date-time":"2024-09-25T00:00:00Z","timestamp":1727222400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Takeda Farmac\u00e9utica Espa\u00f1a S.A."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Fabry disease (FD) is an X-linked lysosomal disease whose ultimate consequences are the accumulation of sphingolipids and subsequent inflammatory events, mainly at the endothelial level. The outcomes include different nervous system manifestations as well as multiple organ damage. Despite the availability of known biomarkers, early detection of FD remains a medical need. This study aimed to develop an in silico model based on machine learning to identify candidate vascular and nervous system proteins for early FD damage detection at the cellular level. A combined systems biology and machine learning approach was carried out considering molecular characteristics of FD to create a computational model of vascular and nervous system disease. A data science strategy was applied to identify risk classifiers by using 10 K-fold cross-validation. Further biological and clinical criteria were used to prioritize the most promising candidates, resulting in the identification of 36 biomarker candidates with classifier abilities, which are easily measurable in body fluids. Among them, we propose four candidates, CAMK2A, ILK, LMNA, and KHSRP, which have high classification capabilities according to our models (cross-validated accuracy \u2265 90%) and are related to the vascular and nervous systems. These biomarkers show promise as high-risk cellular and tissue damage indicators that are potentially applicable in clinical settings, although in vivo validation is still needed.<\/jats:p>","DOI":"10.3390\/ijms251910329","type":"journal-article","created":{"date-parts":[[2024,9,26]],"date-time":"2024-09-26T04:05:46Z","timestamp":1727323546000},"page":"10329","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["In Silico Modeling of Fabry Disease Pathophysiology for the Identification of Early Cellular Damage Biomarker Candidates"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5942-5669","authenticated-orcid":false,"given":"Javier","family":"Gervas-Arruga","sequence":"first","affiliation":[{"name":"Takeda Development Center Americas Inc., Cambridge, MA 02142, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5076-607X","authenticated-orcid":false,"given":"Miguel \u00c1ngel","family":"Barba-Romero","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Albacete University Hospital, 02006 Albacete, Spain"},{"name":"Albacete Medical School, Castilla-La Mancha University, 02006 Albacete, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9391-4316","authenticated-orcid":false,"given":"Jorge Juli\u00e1n","family":"Fern\u00e1ndez-Mart\u00edn","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University Hospital \u00c1lvaro Cunqueiro, 36312 Vigo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3288-5996","authenticated-orcid":false,"given":"Jorge Francisco","family":"G\u00f3mez-Cerezo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Infanta Sof\u00eda University Hospital, 28702 Madrid, Spain"},{"name":"Faculty of Medicine, European University of Madrid, 28670 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8215-872X","authenticated-orcid":false,"given":"Cristina","family":"Seg\u00fa-Verg\u00e9s","sequence":"additional","affiliation":[{"name":"Anaxomics Biotech S.L., 08007 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5310-7694","authenticated-orcid":false,"given":"Giacomo","family":"Ronzoni","sequence":"additional","affiliation":[{"name":"Takeda Farmac\u00e9utica Espa\u00f1a S.A., 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8727-9179","authenticated-orcid":false,"given":"Jorge J.","family":"Cebolla","sequence":"additional","affiliation":[{"name":"Takeda Farmac\u00e9utica Espa\u00f1a S.A., 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/1750-1172-5-30","article-title":"Fabry disease","volume":"5","author":"Germain","year":"2010","journal-title":"Orphanet J. 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