{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:53:14Z","timestamp":1792795994095,"version":"4.5.0"},"reference-count":39,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T00:00:00Z","timestamp":1754265600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012295","name":"NIHR Newcastle Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012295","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014653","name":"Manchester Biomedical Research Centre","doi-asserted-by":"publisher","award":["IS\u2010BRC\u20101215\u201020015"],"award-info":[{"award-number":["IS\u2010BRC\u20101215\u201020015"]}],"id":[{"id":"10.13039\/100014653","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012041","name":"Versus Arthritis","doi-asserted-by":"publisher","award":["21173"],"award-info":[{"award-number":["21173"]}],"id":[{"id":"10.13039\/501100012041","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012041","name":"Versus Arthritis","doi-asserted-by":"publisher","award":["21754"],"award-info":[{"award-number":["21754"]}],"id":[{"id":"10.13039\/501100012041","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012041","name":"Versus Arthritis","doi-asserted-by":"publisher","award":["21755"],"award-info":[{"award-number":["21755"]}],"id":[{"id":"10.13039\/501100012041","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Tumornecrosis factor inhibitors (TNFi) have significantly improved rheumatoid arthritis (RA) management, yet variability in patient response remains a substantial challenge, with approximately 40% of patients discontinuing TNFi due to nonresponse or adverse effects. This study aimed to identify biomarkers predictive of adalimumab treatment response using whole\u2010blood transcriptomics, leveraging machine learning models for data mining observed by targeted statistical analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A cohort of patients with RA starting TNFi therapy (n = 100) was assessed for treatment response at 6 months, with RNA sequencing performed on baseline (pretreatment) and 3\u2010month follow\u2010up samples. Machine learning classifiers were built to identify predictive biomarkers for treatment outcomes. This was observed by a network analysis on the biomarkers to elucidate the most influential biomarker, which was subsequently confirmed through survival analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Differential gene expression analysis in 97 samples passing quality control identified 84 genes associated with treatment response. Random forest classifiers achieved high predictive accuracy with area under the receiver operating characteristic curves up to 0.86, identifying genes contributing to treatment outcomes. Network analysis further elucidated gene interactions, highlighting marginal zone B And B1 cell\u2013specific protein 1 (\n                      <jats:italic>MZB1<\/jats:italic>\n                      ) as a novel biomarker not captured by machine learning alone. MZB1's role in B cell development and antibody production was associated with antidrug antibody formation, impacting treatment efficacy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study advances the understanding of transcriptomic alterations in RA treatment and enhances our understanding of treatment response mechanisms. Although the gene signatures identified require independent replication, the study serves as a starting point to pave the way for personalized therapeutic strategies in patients commencing TNFi therapy in RA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.43255","type":"journal-article","created":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T04:09:14Z","timestamp":1748232554000},"page":"1663-1672","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Identifying Predictive Biomarkers of Response in Patients With Rheumatoid Arthritis Treated With Adalimumab Using Machine Learning Analysis of Whole\u2010Blood Transcriptomics Data"],"prefix":"10.1002","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5256-5642","authenticated-orcid":false,"given":"Chuan Fu","family":"Yap","sequence":"first","affiliation":[{"name":"Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, The University of Manchester  Manchester United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nisha","family":"Nair","sequence":"additional","affiliation":[{"name":"Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, The University of Manchester and NIHR Biomedical Research Centre Manchester  Manchester United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann W.","family":"Morgan","sequence":"additional","affiliation":[{"name":"School of Medicine University of Leeds and NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust  Leeds United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John D.","family":"Isaacs","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute, Newcastle University and NIHR Newcastle Biomedical Research Centre and Musculoskeletal Unit, Newcastle\u2010upon\u2010Tyne Hospitals NHS Foundation Trust, Newcastle\u2010upon\u2010Tyne  United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4855-3926","authenticated-orcid":false,"given":"Anthony G.","family":"Wilson","sequence":"additional","affiliation":[{"name":"School of Medicine and Medical Science, Conway Institute, University College Dublin  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimme","family":"Hyrich","sequence":"additional","affiliation":[{"name":"NIHR Biomedical Research Centre Manchester and Centre for Epidemiology Versus Arthritis, Centre for Musculoskeletal Research, The University of Manchester  Manchester United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2103-1028","authenticated-orcid":false,"given":"Guillermo","family":"Barturen","sequence":"additional","affiliation":[{"name":"GENYO, Centre for Genomics and Oncological Research Pfizer, University of Granada, Andalusian Regional Government, Parque Tecnol\u00f3gico de la Salud (PTS) Granada and Department of Genetics, Faculty of Science University of Granada and Bioinformatics Laboratory, Biotechnology Institute, Centro de Investigaci\u00f3n Biom\u00e9dica, PTS  Granada Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Riva\u2010Torrubia","sequence":"additional","affiliation":[{"name":"Centre for Genomics and Oncology Research (GENYO), Centre for Genomics and Oncological Research Pfizer, University of Granada, Andalusian Regional Government, PTS Granada  Granada Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Gut","sequence":"additional","affiliation":[{"name":"CNAG and Universitat de Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivo","family":"Gut","sequence":"additional","affiliation":[{"name":"CNAG and Universitat de Barcelona  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