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Aberrant DNA methylation has rapidly emerged as a diagnostic and prognostic signature in many cancers. However, such DNA methylation signature available in UVM remains limited. In this study, we performed a genome-wide integrative analysis of methylome and transcriptome and identified 40 methylation-driven prognostic genes (MDPGs) associated with the tumorigenesis and progression of UVM. Then, we proposed a machine-learning-based discovery and validation strategy to identify a DNA methylation-driven signature (10MeSig) composing of 10 MDPGs (AZGP1, BAI1, CCDC74A, FUT3, PLCD1, S100A4, SCN8A, SEMA3B, SLC25A38 and SLC44A3), which stratified 80 patients of the discovery cohort into two risk subtypes with significantly different overall survival (HR\u2009=\u200929, 95% CI: 6.7\u2013126, P\u2009&amp;lt;\u20090.001). The 10MeSig was validated subsequently in an independent cohort with 57 patients and yielded a similar prognostic value (HR\u2009=\u20092.1, 95% CI: 1.2\u20133.7, P\u00a0=\u20090.006). Multivariable Cox regression analysis showed that the 10MeSig is an independent predictive factor for the survival of patients with UVM. With a prospective validation study, this 10MeSig will improve clinical decisions and provide new insights into the pathogenesis of UVM.<\/jats:p>","DOI":"10.1093\/bib\/bbaa371","type":"journal-article","created":{"date-parts":[[2020,11,23]],"date-time":"2020-11-23T20:42:34Z","timestamp":1606164154000},"source":"Crossref","is-referenced-by-count":30,"title":["Machine learning-based integrative analysis of methylome and transcriptome identifies novel prognostic DNA methylation signature in uveal melanoma"],"prefix":"10.1093","volume":"22","author":[{"given":"Ping","family":"Hou","sequence":"first","affiliation":[{"name":"School of Biomedical Engineering, Wenzhou Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siqi","family":"Bao","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering, Wenzhou Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Fan","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering, Wenzhou Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Congcong","family":"Yan","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering, Wenzhou Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianzhong","family":"Su","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering, Wenzhou Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Qu","sequence":"additional","affiliation":[{"name":"School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9987-9024","authenticated-orcid":false,"given":"Meng","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering, Wenzhou Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,12,26]]},"reference":[{"key":"2021072117055423200_ref1","doi-asserted-by":"crossref","first-page":"1664","DOI":"10.1002\/(SICI)1097-0142(19981015)83:8<1664::AID-CNCR23>3.0.CO;2-G","article-title":"The National Cancer Data Base report on cutaneous and noncutaneous melanoma: a summary of 84,836 cases from the past decade. 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