{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T13:38:36Z","timestamp":1773149916314,"version":"3.50.1"},"reference-count":50,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T00:00:00Z","timestamp":1745884800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J of Rheum Dis"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Ankylosing spondylitis (AS) is a chronic inflammatory disease affecting the axial skeleton, characterized by immune microenvironment dysregulation and elevated cytokines like TNF\u2010\u03b1 and IL\u201017. Mitochondrial oxidative phosphorylation (OXPHOS), crucial for immune cell function and survival, is implicated in AS pathogenesis. This study explores OXPHOS\u2010related mechanisms in AS, identifies key genes using machine learning, and highlights potential therapeutic targets for precision medicine.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>Peripheral blood mononuclear cells (PBMCs) bulk transcriptomic and single\u2010cell RNA sequencing (scRNA\u2010seq) data from AS patients were analyzed to investigate the role of the OXPHOS pathway in AS. Weighted gene co\u2010expression network analysis (WGCNA) was performed to identify key gene modules associated with OXPHOS. Machine learning techniques, including support vector machine with recursive feature elimination (SVM\u2010RFE), random forest, and least absolute shrinkage and selection operator (LASSO), were applied to identify significant AS\u2010related genes. Real\u2010time PCR (RT\u2010PCR) was used to quantify gene expression, examine their patterns in specific cell subtypes, and explore their functional implications.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Pathway enrichment analysis identified OXPHOS as a significantly enriched pathway distinguishing AS patients from healthy controls, with high normalized enrichment scores and significant group separation in principal component analysis. ScRNA\u2010seq revealed significantly higher OXPHOS scores in AS patients, especially in dendritic cells (DCs) and monocytes, highlighting cell type\u2010specific dysregulation. WGCNA identified two key gene modules (MEyellow and MEtan) that are closely associated with OXPHOS. Three hub genes\u2014<jats:italic>LAMTOR2<\/jats:italic>, <jats:italic>APBB1IP<\/jats:italic>, and <jats:italic>DGKQ<\/jats:italic>\u2014were screened using machine learning methods and validated by RT\u2010PCR and scRNA\u2010seq. Among them, <jats:italic>LAMTOR2<\/jats:italic> was significantly more highly expressed in patients with AS, and functional analyses showed that it plays a role in promoting TH17 cell differentiation, which highlights its potential as a therapeutic target for ankylosing spondylitis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This multi\u2010omics study provides valuable insights into the complex interplay between OXPHOS and AS. The identified genes, particularly <jats:italic>LAMTOR2<\/jats:italic>, serve as potential therapeutic targets, contributing to our understanding of AS mechanisms and paving the way for precision medicine in AS treatment.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1756-185x.70175","type":"journal-article","created":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T07:35:31Z","timestamp":1745912131000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Oxidative Phosphorylation Pathway in Ankylosing Spondylitis: Multi\u2010Omics Analysis and Machine Learning"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3852-9041","authenticated-orcid":false,"given":"Yuling","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Immunology The Seventh Affiliated Hospital, Sun Yat\u2010Sen University  Shenzhen 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