{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:55:33Z","timestamp":1791204933022,"version":"4.1.0"},"reference-count":37,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>HBOCpred was developed to support research prioritisation of unresolved germline missense variants in a defined 17-gene study panel. Four calibrated learners provide vote states (V0\u2013V4) and a continuous modified adaptive classifier score (SMAC). The same directional descriptors apply to labelled and unresolved records: unanimous benign\/likely benign-directed (V0), mixed (V1\u2013V3), and unanimous likely pathogenic\/pathogenic-directed (V4) votes. Development used 2160 anchors and five repeats of nested five-fold cross-validation, with preprocessing fitted within training partitions. The annotation-completeness rule permitted evaluation of 2046 anchors per repeat. Mean balanced accuracy for the secondary \u22653-of-4 endpoint was 0.9604; mean SMAC area under the receiver operating characteristic curve (AUROC) and Brier score were 0.9909 and 0.0294. In the first repeat, unanimity covered 1968\/2160 anchors (91.11%), with source-label agreement in 1920\/1968 unanimous outputs (97.56%). Leave-one-gene-out AUROC was 0.9812 among 2045 evaluable anchors, with substantial gene-specific variation. Among 43,679 unresolved records, V0, V1\u2013V3, and V4 contained 33,414, 4491 and 5774 variants, respectively. HBOCpred makes learner agreement and disagreement available for expert review and functional follow-up. Independent validation is needed to assess its performance and utility in unresolved variants.<\/jats:p>","DOI":"10.3390\/ijms27198865","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:31:31Z","timestamp":1791203491000},"page":"8865","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["HBOCpred: An Ensemble Framework for Prioritisation of Germline Missense Variants in Hereditary Breast and Ovarian Cancer"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1563-2292","authenticated-orcid":false,"given":"Mustafa Tar\u0131k","family":"Alay","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, Ankara Etlik City Hospital, 06170 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4391-1387","authenticated-orcid":false,"given":"Haktan Ba\u011f\u0131\u015f","family":"Erdem","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Ankara Etlik City Hospital, 06170 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"key":"ref_1","first-page":"93","article-title":"Analysis of the Results of the BRCA1 and BRCA2 Genes in Early-Onset Breast Cancer Patients from the Ordu Province","volume":"6","author":"Akosman","year":"2026","journal-title":"Atl. 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