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Numerous studies have evaluated the diagnostic value of blood biomarkers but with disappointing results. Thus, the gold standard for diagnosing endometriosis remains laparoscopy. We performed a prospective trial, the ENDO-miRNA study, using both Artificial Intelligence (AI) and Machine Learning (ML), to analyze the current human miRNome to differentiate between patients with and without endometriosis, and to develop a blood-based microRNA (miRNA) diagnostic signature for endometriosis. Here, we present the first blood-based diagnostic signature obtained from a combination of two robust and disruptive technologies merging the intrinsic quality of miRNAs to condense the endometriosis phenotype (and its heterogeneity) with the modeling power of AI. The most accurate signature provides a sensitivity, specificity, and Area Under the Curve (AUC) of 96.8%, 100%, and 98.4%, respectively, and is sufficiently robust and reproducible to replace the gold standard of diagnostic surgery. Such a diagnostic approach for this debilitating disorder could impact recommendations from national and international learned societies.<\/jats:p>","DOI":"10.1038\/s41598-022-07771-7","type":"journal-article","created":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T11:04:59Z","timestamp":1646737499000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["MicroRNome analysis generates a blood-based signature for endometriosis"],"prefix":"10.1038","volume":"12","author":[{"given":"Sofiane","family":"Bendifallah","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yohann","family":"Dabi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phane","family":"Suisse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludmila","family":"Jornea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delphine","family":"Bouteiller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyril","family":"Touboul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Puchar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emile","family":"Dara\u00ef","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,3,8]]},"reference":[{"issue":"25","key":"7771_CR1","doi-asserted-by":"publisher","first-page":"2389","DOI":"10.1056\/NEJMcp1000274","volume":"362","author":"LC Giudice","year":"2010","unstructured":"Giudice, L. 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