{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:00:47Z","timestamp":1785416447879,"version":"3.56.0"},"reference-count":52,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:00:00Z","timestamp":1775692800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["62372099"],"award-info":[{"award-number":["62372099"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"award":["62372099"],"award-info":[{"award-number":["62372099"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"the Jilin Scientific and Technological Development Program","award":["20260203028SF"],"award-info":[{"award-number":["20260203028SF"]}]},{"name":"Key Laboratory of Intelligent Rehabilitation and Barrier-free for the Disabled (Changchun University), Ministry of Education","award":["2024KFJJ003"],"award-info":[{"award-number":["2024KFJJ003"]}]},{"award":["2024KFJJ003"],"award-info":[{"award-number":["2024KFJJ003"]}],"id":[{"id":"https:\/\/ror.org\/05tqgjy81","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Osteoarthritis (OA) is a complex degenerative joint disease for which early diagnosis and clear molecular characterization remain limited. DNA methylation has been increasingly recognized as an important regulatory factor in OA pathogenesis. In this study, we proposed an integrative computational framework combining statistical analysis, machine learning, deep learning, and functional genomics to identify and validate OA-associated genes and methylation biomarkers for diagnostic and biological interpretation. Candidate CpG sites were obtained using two complementary strategies: differential methylation analysis and selection of loci located near transcription start sites of previously reported OA-related genes. Key features were further refined using support vector machine recursive feature elimination and random forest algorithms. Based on the selected loci, we developed a feature-fusion diagnostic model that combines Transformer and convolutional neural networks with adaptive weighting to capture both global dependency structures and local methylation patterns. A panel of 220 methylation sites demonstrated stable and reproducible diagnostic performance in an independent cohort. Functional annotation and pathway analysis highlighted several established OA-associated genes, including TGFBR2, SMAD3, PPARG, and MAPK3, and suggested INHBB as a potential novel effector gene, with additional support for AMH and INHBE involvement. Overall, this study presents a robust methylation-based framework for identifying key OA-associated genes and provides new insights into the epigenetic mechanisms underlying OA.<\/jats:p>","DOI":"10.3390\/ijms27083388","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T07:55:12Z","timestamp":1775807712000},"page":"3388","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of Key Osteoarthritis-Associated Genes Based on DNA Methylation"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3265-6461","authenticated-orcid":false,"given":"Jian","family":"Zhao","sequence":"first","affiliation":[{"name":"School of Computer Science and Technology, Changchun University, Changchun 130022, China"},{"name":"Jilin Provincial Key Laboratory of Human Health Status Identification Function & Enhancement, Changchun 130022, China"},{"name":"Key Laboratory of Intelligent Rehabilitation and Barrier-Free for the Disabled, Changchun University, Ministry of Education, Changchun 130022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changwu","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Computer Science and Technology, Changchun University, Changchun 130022, China"},{"name":"Jilin Provincial Key Laboratory of Human Health Status Identification Function & Enhancement, Changchun 130022, China"},{"name":"Key Laboratory of Intelligent Rehabilitation and Barrier-Free for the Disabled, Changchun University, Ministry of Education, Changchun 130022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5632-7596","authenticated-orcid":false,"given":"Zhejun","family":"Kuang","sequence":"additional","affiliation":[{"name":"School of Computer Science and Technology, Changchun University, Changchun 130022, China"},{"name":"Jilin Provincial Key Laboratory of Human Health Status Identification Function & Enhancement, Changchun 130022, China"},{"name":"Key Laboratory of Intelligent Rehabilitation and Barrier-Free for the Disabled, Changchun University, Ministry of Education, Changchun 130022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4302-1886","authenticated-orcid":false,"given":"Han","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Information Science and Technology, Institute of Computational Biology, Northeast Normal University, Changchun 130117, China"},{"name":"School of Elite Biomedical Engineers, China Pharmaceutical University, Nanjing 210009, China"},{"name":"Ningxia Key Laboratory of Bioimaging and Intelligent Diagnostics, Yinchuan 750021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijuan","family":"Shi","sequence":"additional","affiliation":[{"name":"Jilin Provincial Key Laboratory of Human Health Status Identification Function & Enhancement, Changchun 130022, China"},{"name":"Key Laboratory of Intelligent Rehabilitation and Barrier-Free for the Disabled, Changchun University, Ministry of Education, Changchun 130022, China"},{"name":"College of Electronic Information Engineering, Changchun University, Changchun 130022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.1016\/S0140-6736(24)00757-8","article-title":"Global incidence, prevalence, years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations, 1990\u20132021: A systematic analysis for the Global Burden of Disease Study 2021","volume":"403","author":"Ferrari","year":"2024","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e508","DOI":"10.1016\/S2665-9913(23)00163-7","article-title":"Global, regional, and national burden of osteoarthritis, 1990\u20132020 and projections to 2050: A systematic analysis for the Global Burden of Disease Study 2021","volume":"5","author":"Steinmetz","year":"2023","journal-title":"Lancet Rheumatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1038\/s41392-025-02556-6","article-title":"Osteoarthritis: Molecular pathogenesis and potential therapeutic options","volume":"11","author":"Zhang","year":"2026","journal-title":"Sig. 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