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We used deletion structural variants (DSVs) generated from germline whole-genome sequencing (WGS) and DSV immune-related association tumor microenvironment (TME) to predict cancer risk and prognosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We investigated the contribution of germline DSVs to cancer susceptibility and prognosis by silicon and causal inference models. DSVs in germline WGS data were generated from the blood samples of 192 cancer and 499 non-cancer subjects. Clinical information, including family cancer history (FCH), was obtained from the National Cheng Kung University Hospital and Taiwan Biobank. Ninety-nine colorectal cancer (CRC) patients had immune response gene expression data. We used joint calling tools and an attention-weighted model to build the cancer risk predictive model and identify DSVs in familial cancer. The survival support vector machine (survival-SVM) was used to select prognostic DSVs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified 671 DSVs that could predict cancer risk. The area under the curve (AUC) of the receiver operating characteristic curve (ROC) of the attention-weighted model was 0.71. The 3 most frequent DSV genes observed in cancer patients were identified as\n                      <jats:italic>ADCY9<\/jats:italic>\n                      ,\n                      <jats:italic>AURKAPS1<\/jats:italic>\n                      , and\n                      <jats:italic>RAB3GAP2<\/jats:italic>\n                      (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.05). The DSVs in\n                      <jats:italic>SGSM2<\/jats:italic>\n                      and\n                      <jats:italic>LHFPL3<\/jats:italic>\n                      were relevant to colorectal cancer. We found a higher incidence of FCH in cancer patients than in non-cancer subjects (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.05).\n                      <jats:italic>SMYD3<\/jats:italic>\n                      and\n                      <jats:italic>NKD2DSV<\/jats:italic>\n                      genes were associated with cancer patients with FCH (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.05). We identified 65 immune-associated DSV markers for assessing cancer prognosis (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.05). The functional protein of\n                      <jats:italic>MUC4<\/jats:italic>\n                      DSV gene interacted with\n                      <jats:italic>MAGE1<\/jats:italic>\n                      expression, according to the STRING database. The causal inference model showed that deleting the\n                      <jats:italic>CEP72<\/jats:italic>\n                      DSV gene affect the recurrence-free survival (RFS) of\n                      <jats:italic>IFIT1<\/jats:italic>\n                      expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We established an explainable attention-weighted model for cancer risk prediction and used the survival-SVM for prognostic stratification by using germline DSVs and immune gene expression datasets. Comprehensive assessments of germline DSVs can predict the cancer risk and clinical outcome of colon cancer patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40246-020-00302-3","type":"journal-article","created":{"date-parts":[[2021,1,11]],"date-time":"2021-01-11T08:28:51Z","timestamp":1610353731000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Comprehensive assessments of germline deletion structural variants reveal the association between prognostic MUC4 and CEP72 deletions and immune response gene expression in colorectal cancer patients"],"prefix":"10.1186","volume":"15","author":[{"given":"Peng-Chan","family":"Lin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui-O","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chih-Jung","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Min","family":"Yeh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meng-Ru","family":"Shen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jung-Hsien","family":"Chiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,1,11]]},"reference":[{"key":"302_CR1","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1038\/s41416-019-0393-x","volume":"120","author":"M Escala-Garcia","year":"2019","unstructured":"Escala-Garcia M, Guo Q, D\u00f6rk T, Canisius S, Keeman R, Dennis J, et al. 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All participants provided written informed consent.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"3"}}