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However, it remains a challenge to predict HRD status precisely and economically. Copy number alteration (CNA), as a pervasive trait of human cancers, can be extracted from a variety of data sources, including whole genome sequencing (WGS), SNP array, and panel sequencing, and thus can be easily applied clinically. Here we systematically evaluate the predictive performance of various CNA features and signatures in HRD prediction and build a gradient boosting machine model (HRD<jats:sub>CNA<\/jats:sub>) for pan-cancer HRD prediction based on these CNA features. CNA features BP10MB[1] (The number of breakpoints per 10MB of DNA is 1) and SS[\u2009&gt;\u20097 &amp; &lt;=8] (The log10-based size of segments is greater than 7 and less than or equal to 8) are identified as the most important features in HRD prediction. HRD<jats:sub>CNA<\/jats:sub>suggests the biallelic inactivation of<jats:italic>BRCA1<\/jats:italic>,<jats:italic>BRCA2<\/jats:italic>,<jats:italic>PALB2<\/jats:italic>,<jats:italic>RAD51C<\/jats:italic>,<jats:italic>RAD51D<\/jats:italic>, and<jats:italic>BARD1<\/jats:italic>as the major genetic basis for human HRD, and may also be applied to effectively validate the pathogenicity of BRCA1\/2 variants of uncertain significance (VUS). Together, this study provides a robust tool for cost-effective HRD prediction and also demonstrates the applicability of CNA features and signatures in cancer precision medicine.<\/jats:p>","DOI":"10.1038\/s42003-023-04901-3","type":"journal-article","created":{"date-parts":[[2023,5,16]],"date-time":"2023-05-16T11:02:39Z","timestamp":1684234959000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Copy number alteration features in pan-cancer homologous recombination deficiency prediction and biology"],"prefix":"10.1038","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7452-3168","authenticated-orcid":false,"given":"Huizi","family":"Yao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huimin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8999-9628","authenticated-orcid":false,"given":"Tao","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Ning","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaixuan","family":"Diao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenxu","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangshuai","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3272-1227","authenticated-orcid":false,"given":"Ziyu","family":"Tao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangyu","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqin","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7736-0077","authenticated-orcid":false,"given":"Xue-Song","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,5,16]]},"reference":[{"key":"4901_CR1","doi-asserted-by":"publisher","first-page":"2154","DOI":"10.1056\/NEJMoa1611310","volume":"375","author":"MR Mirza","year":"2016","unstructured":"Mirza, M. 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