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Clinically driven molecular profiling studies may cover these gaps. We performed DNA sequencing (DNAseq) and RNA sequencing (RNAseq), portraying the molecular profile of 102 samples of 3 of the most common STS subtypes. The RNAseq data was analyzed using unsupervised machine learning models, unravelling previously unknown molecular patterns and identifying 4 well-defined transcriptomic clusters. These transcriptomic clusters have a clear prognostic value, a finding that was externally validated. This transcriptomic cluster-based classification\u2019s prognostic value is superior to the prognostic accuracy of currently used clinical-based (SARCULATOR nomograms) and molecular-based (CINSARC) prognostication tools. The analysis of DNAseq data from the same cohort of samples revealed a plethora of unique and, in some cases, never documented molecular targets for precision treatment across different transcriptomic clusters.<\/jats:p>","DOI":"10.1101\/2025.01.31.25321492","type":"posted-content","created":{"date-parts":[[2025,2,2]],"date-time":"2025-02-02T20:10:24Z","timestamp":1738527024000},"source":"Crossref","is-referenced-by-count":1,"title":["Machine learning-based analysis of genomic and transcriptomic data unveils sarcoma clusters with superlative prognostic and predictive value"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6858-7341","authenticated-orcid":false,"given":"Miguel","family":"Esperan\u00e7a-Martins","sequence":"first","affiliation":[]},{"given":"Hugo","family":"Vasques","sequence":"additional","affiliation":[]},{"given":"Manuel Sokolov","family":"Ravasqueira","sequence":"additional","affiliation":[]},{"given":"Maria Manuel","family":"Lemos","sequence":"additional","affiliation":[]},{"given":"Filipa","family":"Fonseca","sequence":"additional","affiliation":[]},{"given":"Diogo","family":"Coutinho","sequence":"additional","affiliation":[]},{"given":"Jorge Antonio","family":"L\u00f3pez","sequence":"additional","affiliation":[]},{"given":"Richard S.P.","family":"Huang","sequence":"additional","affiliation":[]},{"given":"S\u00e9rgio","family":"Dias","sequence":"additional","affiliation":[]},{"given":"Lina","family":"Gallego-Paez","sequence":"additional","affiliation":[]},{"given":"Lu\u00eds","family":"Costa","sequence":"additional","affiliation":[]},{"given":"Nuno","family":"Abecasis","sequence":"additional","affiliation":[]},{"given":"Emanuel","family":"Gon\u00e7alves","sequence":"additional","affiliation":[]},{"given":"Isabel","family":"Fernandes","sequence":"additional","affiliation":[]}],"member":"54368","reference":[{"issue":"3","key":"2025020408450893000_2025.01.31.25321492v1.1","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1001\/jamaoncol.2018.6766","article-title":"Triassic Cancer\u2014Osteosarcoma in a 240-Million-Year-Old Stem-Turtle","volume":"5","year":"2019","journal-title":"JAMA Oncol"},{"key":"2025020408450893000_2025.01.31.25321492v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2021.07.006"},{"key":"2025020408450893000_2025.01.31.25321492v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2021.08.1995"},{"key":"2025020408450893000_2025.01.31.25321492v1.4","first-page":"925","article-title":"More than 50 subtypes of soft tissue sarcoma: paving the path for histology-driven treatments","volume":"38","year":"2018","journal-title":"Am Soc Clin Oncol Educ Book"},{"key":"2025020408450893000_2025.01.31.25321492v1.5","doi-asserted-by":"crossref","unstructured":"Connolly, E.A. , Grimison, P.S. , Horvath, L.G. , et al. 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