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Diagnosis of ME\/CFS remains challenging, with most patients relying on self\u2010report, questionnaires, and subjective measures to receive a diagnosis, and many never receiving a clear diagnosis at all. In this study, a single\u2010cell Raman platform and artificial intelligence are utilized to analyze blood cells from 98 human subjects, including 61 ME\/CFS patients of varying disease severity and 37 healthy and disease controls. These results demonstrate that Raman profiles of blood cells can distinguish between healthy individuals, disease controls, and ME\/CFS patients with high accuracy (91%), and can further differentiate between mild, moderate, and severe ME\/CFS patients (84%). Additionally, specific Raman peaks that correlate with ME\/CFS phenotypes and have the potential to provide insights into biological changes and support the development of new therapeutics are identified. This study presents a promising approach for aiding in the diagnosis and management of ME\/CFS and can be extended to other unexplained chronic diseases such as long COVID and post\u2010treatment Lyme disease syndrome, which share many of the same symptoms as ME\/CFS.<\/jats:p>","DOI":"10.1002\/advs.202302146","type":"journal-article","created":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T00:20:39Z","timestamp":1693527639000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Developing a Blood Cell\u2010Based Diagnostic Test for Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome Using Peripheral Blood Mononuclear Cells"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1285-9408","authenticated-orcid":false,"given":"Jiabao","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Engineering Science University of Oxford  Parks Road Oxford OX1 3PJ UK"},{"name":"Division of Biomedical Engineering, James Watt School of Engineering University of Glasgow  Glasgow G12 8LT UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany","family":"Lodge","sequence":"additional","affiliation":[{"name":"Nuffield Department of Women's and Reproductive Health University of Oxford The Women Centre John Radcliffe Hospital  Headley Way, Headington Oxford OX3 9DU UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Kingdon","sequence":"additional","affiliation":[{"name":"Faculty of Infectious Diseases London School of Hygiene and Tropical Medicine  Keppel St London WC1E 7HT UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James W. 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