{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T09:13:20Z","timestamp":1780564400091,"version":"3.54.1"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,11]],"date-time":"2026-01-11T00:00:00Z","timestamp":1768089600000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["HemaSphere"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    We applied supervised and unsupervised machine learning (ML) analyses to a cohort of 140 patients referred to the Hematology Unit of the G. Gaslini Institute from 1989 to 2023 for persistent cytopenia and\/or features suggestive of telomere biology disorders (TBDs). Patients were labeled as \u201cTBD\u201d (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200920, established molecular diagnosis of TBD), \u201cother diagnosis\u201d (OD,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200927, established molecular diagnosis of congenital disease including marrow failures), and \u201cundefined diagnosis\u201d (UD,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200993, no established molecular diagnosis). After training a random forest model on 47 patients with established molecular diagnosis (20 TBD and 27 OD), supervised analysis was applied to the UD group and predicted 16\/93 patients as having potential TBD and 77\/93 subjects with potential OD, accounting for 17.2% and 82.7% of possibly reallocated diagnoses, respectively. The unsupervised approach applied to the whole cohort (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009140) identified 4 distinct clusters to be significantly associated (P\u2009=\u20090.000001) with 47 molecular diagnoses, with TBD patients prevailing in Clusters 1 and 2 and OD patients in Clusters 3 and 4. Telomere length (TL) and mucocutaneous abnormalities were the most relevant drivers in discriminating between the TBD and OD groups in supervised and unsupervised analyses; they prevailed in Clusters 1 and 2. Interestingly, both analyses yielded similar results in the UD group, where all 16\/93 patients without molecular diagnosis predicted to have TBD in the supervised approach were placed in \u201cTBD clusters\u201d 1\u20132 of the unsupervised analysis. This model might correctly reallocate a remarkable proportion of undefined or previously misclassified cases, thus potentially leading to substantially improved diagnostic work\u2010up of rare and challenging diseases like TBD.\n                  <\/jats:p>","DOI":"10.1002\/hem3.70272","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T07:17:53Z","timestamp":1768202273000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Application of machine learning in the diagnostic work\u2010up of telomere biology disorders"],"prefix":"10.1002","volume":"10","author":[{"given":"Erika","family":"Massaccesi","sequence":"first","affiliation":[{"name":"Hematology Unit IRCCS Istituto Giannina Gaslini Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Arcuri","sequence":"additional","affiliation":[{"name":"Hematology Unit IRCCS Istituto Giannina Gaslini Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo","family":"Cavalca","sequence":"additional","affiliation":[{"name":"Clinical Bioinformatics Unit IRCCS Istituto Giannina Gaslini Genoa Italy"},{"name":"Department of Computer Science and Engineering University of Bologna Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabian","family":"Beier","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology, Hemostaseology, Stem Cell Transplantation, Medical Faculty, Center for Integrated Oncology (CIO) RWTH Aachen University Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Vankann","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology, Hemostaseology, Stem Cell Transplantation, Medical Faculty, Center for Integrated Oncology (CIO) RWTH Aachen University Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Lupia","sequence":"additional","affiliation":[{"name":"Hematology Unit IRCCS Istituto Giannina Gaslini Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Cangelosi","sequence":"additional","affiliation":[{"name":"Clinical Bioinformatics Unit IRCCS Istituto Giannina Gaslini Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Grossi","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics and Genomics of Rare Diseases IRCCS Istituto Giannina Gaslini Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Lanciotti","sequence":"additional","affiliation":[{"name":"Hematology Unit IRCCS Istituto Giannina Gaslini Genoa 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Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Carla","family":"Giarratana","sequence":"additional","affiliation":[{"name":"Hematology Unit IRCCS Istituto Giannina Gaslini Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Guardo","sequence":"additional","affiliation":[{"name":"Hematology Unit IRCCS Istituto Giannina Gaslini Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Bagnasco","sequence":"additional","affiliation":[{"name":"Biostatistics Unit, Scientific Directorate IRCCS Istituto Giannina Gaslini Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Pestarino","sequence":"additional","affiliation":[{"name":"Hematopoietic Stem Cell Transplantation Unit IRCCS Istituto Giannina Gaslini Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Binelli","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health University of Genoa Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mareike","family":"Tometten","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology, Hemostaseology, Stem Cell Transplantation, Medical Faculty, Center for Integrated Oncology (CIO) RWTH Aachen University Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5693-2216","authenticated-orcid":false,"given":"Robert","family":"Meyer","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology, Hemostaseology, Stem Cell Transplantation, Medical Faculty, Center for Integrated Oncology (CIO) RWTH Aachen University Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanny","family":"Frenzel","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology, Hemostaseology, Stem Cell Transplantation, Medical Faculty, Center for Integrated Oncology (CIO) RWTH Aachen University Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico","family":"Coviello","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics IRCCS Istituto Giannina Gaslini Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugenia","family":"Mariani","sequence":"additional","affiliation":[{"name":"Hematology Unit IRCCS Istituto Giannina Gaslini Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Palmisani","sequence":"additional","affiliation":[{"name":"Hematology Unit IRCCS Istituto Giannina Gaslini Genoa 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