{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T14:24:17Z","timestamp":1788531857866,"version":"build-2803163510"},"reference-count":69,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/01gavpb45","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014224","name":"Open Medicine Foundation","doi-asserted-by":"crossref","award":["#E9287"],"award-info":[{"award-number":["#E9287"]}],"id":[{"id":"10.13039\/100014224","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Fonds de Recherche du Qu\u00e9bec\u2014Sant\u00e9","award":["#32600"],"award-info":[{"award-number":["#32600"]}]},{"award":["#32600"],"award-info":[{"award-number":["#32600"]}],"id":[{"id":"https:\/\/ror.org\/02eqrsj93","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["#ALLRP 555121-20"],"award-info":[{"award-number":["#ALLRP 555121-20"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"award":["#ALLRP 555121-20"],"award-info":[{"award-number":["#ALLRP 555121-20"]}],"id":[{"id":"https:\/\/ror.org\/01h531d29","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000196","name":"Canadian Foundation for Innovation","doi-asserted-by":"publisher","award":["#40880"],"award-info":[{"award-number":["#40880"]}],"id":[{"id":"10.13039\/501100000196","id-type":"DOI","asserted-by":"publisher"}]},{"award":["#40880"],"award-info":[{"award-number":["#40880"]}],"id":[{"id":"https:\/\/ror.org\/000az4664","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Myalgic encephalomyelitis (ME) is characterized by profound fatigue, post-exertional malaise (PEM), and cognitive dysfunction. Despite its clinical significance, the pathophysiology of PEM and disease heterogeneity remain unclear, and no validated biomarkers are available for rapid diagnosis or monitoring. We aimed to develop a screening approach combining label-free Raman spectroscopy (RS) and machine learning modeling (ML) to detect biomolecular changes in blood plasma and differentiate patients with ME from sedentary healthy controls. Blood plasma was collected from 115 patients with ME and 45 controls at rest (T0) and 90 min after a standardized, non-invasive stress test designed to induce PEM. Plasma samples were analyzed by RS, and ML models were developed independently at each time point to differentiate patients with ME and controls. The RS-ML models identified spectral features consistent with contributions from proteins, lipids, and low-molecular-weight metabolites. At T0 and T90, the area under the receiver operating characteristic curve, accuracy, specificity and sensitivity were 0.85 and 0.83, 79% and 84%, 82% and 90%, and 73% and 69%, respectively. RS-ML provides a rapid, low-cost approach to detect ME-associated biomolecular signatures in plasma and capture biochemical alterations associated with standardized stress.<\/jats:p>","DOI":"10.3390\/ijms27114937","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T12:45:08Z","timestamp":1780404308000},"page":"4937","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Raman Spectroscopy Combined with Machine Learning Reveals Myalgic Encephalomyelitis\u2013Associated Biomolecular Signatures at Rest and After Standardized Stress"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-7986-1477","authenticated-orcid":false,"given":"Maryam","family":"Heidarifard","sequence":"first","affiliation":[{"name":"Azrieli Research Center, CHU Sainte-Justine, Montreal, QC H3T 1C5, Canada"},{"name":"Research Center, CHUM, Montreal, QC H2X 0A9, Canada"},{"name":"Institute of Biomedical Engineering, Universit\u00e9 de Montr\u00e9al, Montreal, QC H3T 1J4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5549-6603","authenticated-orcid":false,"given":"Atefeh","family":"Moezzi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Medicine, Faculty of Medicine, Universit\u00e9 de Montr\u00e9al, Montreal, QC H3T 1J4, Canada"},{"name":"Viscogliosi Laboratory in Molecular Genetics of Musculoskeletal Diseases, Azrieli Research Center, CHU Sainte-Justine, Montreal, QC H3T 1C5, Canada"},{"name":"Open Medicine Foundation ME Collaborative Center, CHU Sainte-Justine\/Universit\u00e9 de 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Canada"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Katherine","family":"Ember","sequence":"additional","affiliation":[{"name":"Research Center, CHUM, Montreal, QC H2X 0A9, Canada"},{"name":"Department of Engineering Physics, Polytechnique Montreal, Montreal, QC H3T 0A3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3577-3551","authenticated-orcid":false,"given":"Wesam","family":"Elremaly","sequence":"additional","affiliation":[{"name":"Viscogliosi Laboratory in Molecular Genetics of Musculoskeletal Diseases, Azrieli Research Center, CHU Sainte-Justine, Montreal, QC H3T 1C5, Canada"},{"name":"Open Medicine Foundation ME Collaborative Center, CHU Sainte-Justine\/Universit\u00e9 de Montr\u00e9al, Montreal, QC H3T 1C5, Canada"},{"name":"ICanCME Research Network, Azrieli Research Center, CHU Sainte-Justine, Montreal, QC H3T 1C5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Iurie","family":"Caraus","sequence":"additional","affiliation":[{"name":"Viscogliosi Laboratory in Molecular Genetics of Musculoskeletal Diseases, Azrieli Research Center, CHU Sainte-Justine, Montreal, QC H3T 1C5, Canada"},{"name":"Open Medicine Foundation ME Collaborative Center, CHU Sainte-Justine\/Universit\u00e9 de Montr\u00e9al, Montreal, QC H3T 1C5, Canada"},{"name":"ICanCME Research Network, Azrieli Research Center, CHU Sainte-Justine, Montreal, QC H3T 1C5, 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