{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T02:46:02Z","timestamp":1773110762329,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1010204","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,7,26]],"date-time":"2022-07-26T00:00:00Z","timestamp":1658793600000}}],"reference-count":68,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2022,7,5]],"date-time":"2022-07-05T00:00:00Z","timestamp":1656979200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Vice-Chancellor\u2019s Research Scholarship (VCRS), Ulster University"},{"name":"European Union Regional Development Fund"},{"name":"EU Sustainable Competitiveness Programme for Northern Ireland & the Northern Ireland Public Health Agency"},{"DOI":"10.13039\/501100001632","name":"Ulster University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001632","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Innovate UK NxNW ICURe programme"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>Rheumatoid arthritis (RA) is a chronic autoimmune condition, characterised by joint pain, damage and disability, which can be addressed in a high proportion of patients by timely use of targeted biologic treatments. However, the patients, non-responsive to the treatments often suffer from refractoriness of the disease, leading to poor quality of life. Additionally, the biologic treatments are expensive. We obtained plasma samples from N = 144 participants with RA, who were about to commence anti-tumour necrosis factor (anti-TNF) therapy. These samples were sent to Olink Proteomics, Uppsala, Sweden, where proximity extension assays of 4 panels, containing 92 proteins each, were performed. A total of n = 89 samples of patients passed the quality control of anti-TNF treatment response data. The preliminary analysis of plasma protein expression values suggested that the RA population could be divided into two distinct molecular sub-groups (endotypes). However, these broad groups did not predict response to anti-TNF treatment, but were significantly different in terms of gender and their disease activity. We then labelled these patients as responders (n = 60) and non-responders (n = 29) based on the change in disease activity score (DAS) after 6 months of anti-TNF treatment and applied machine learning (ML) with a rigorous 5-fold nested cross-validation scheme to filter 17 proteins that were significantly associated with the treatment response. We have developed a ML based classifier ATRPred (anti-TNF treatment response predictor), which can predict anti-TNF treatment response in RA patients with 81% accuracy, 75% sensitivity and 86% specificity. ATRPred may aid clinicians to direct anti-TNF therapy to patients most likely to receive benefit, thus save cost as well as prevent non-responsive patients from refractory consequences. ATRPred is implemented in R.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1010204","type":"journal-article","created":{"date-parts":[[2022,7,5]],"date-time":"2022-07-05T18:21:25Z","timestamp":1657045285000},"page":"e1010204","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":20,"title":["ATRPred: A machine learning based tool for clinical decision making of anti-TNF treatment in rheumatoid arthritis patients"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7383-2460","authenticated-orcid":true,"given":"Bodhayan","family":"Prasad","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5894-6988","authenticated-orcid":true,"given":"Cathy","family":"McGeough","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8543-0696","authenticated-orcid":true,"given":"Amanda","family":"Eakin","sequence":"additional","affiliation":[]},{"given":"Tan","family":"Ahmed","sequence":"additional","affiliation":[]},{"given":"Dawn","family":"Small","sequence":"additional","affiliation":[]},{"given":"Philip","family":"Gardiner","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4678-6486","authenticated-orcid":true,"given":"Adrian","family":"Pendleton","sequence":"additional","affiliation":[]},{"given":"Gary","family":"Wright","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1105-7147","authenticated-orcid":true,"given":"Anthony J.","family":"Bjourson","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3547-5551","authenticated-orcid":true,"given":"David S.","family":"Gibson","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4985-9305","authenticated-orcid":true,"given":"Priyank","family":"Shukla","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2022,7,5]]},"reference":[{"key":"pcbi.1010204.ref001","doi-asserted-by":"crossref","first-page":"18001","DOI":"10.1038\/nrdp.2018.1","article-title":"Rheumatoid arthritis.","volume":"4","author":"JS Smolen","year":"2018","journal-title":"Nat Rev Dis Primers"},{"issue":"4","key":"pcbi.1010204.ref002","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1111\/j.1476-5381.2010.01099.x","article-title":"Treatment of rheumatoid arthritis with tumour necrosis factor inhibitors","volume":"162","author":"D Mewar","year":"2011","journal-title":"Br J Pharmacol"},{"issue":"1","key":"pcbi.1010204.ref003","doi-asserted-by":"crossref","first-page":"e135","DOI":"10.1038\/ctg.2015.63","article-title":"Loss of response to anti-TNFs: definition, epidemiology, and management.","volume":"7","author":"G Roda","year":"2016","journal-title":"Clin Transl Gastroenterol"},{"key":"pcbi.1010204.ref004","article-title":"Common characteristics in RA patients who don\u2019t respond to biologics","author":"V. 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