{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T18:44:03Z","timestamp":1776278643576,"version":"3.50.1"},"reference-count":64,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T00:00:00Z","timestamp":1759104000000},"content-version":"vor","delay-in-days":29,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005046","name":"Natural Science Foundation of Heilongjiang Province of China","doi-asserted-by":"crossref","award":["LH2020F046"],"award-info":[{"award-number":["LH2020F046"]}],"id":[{"id":"10.13039\/501100005046","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Double First Class Discipline Collaborative Innovation foundation of Heilongjiang province of China","award":["LJGXCG2023-54"],"award-info":[{"award-number":["LJGXCG2023-54"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,8,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Protein kinases regulate diverse cellular functions, including cell cycle progression, metabolism, differentiation, and survival, with their dysregulation implicated in multiple carcinogenic processes. Phosphatidylinositol 3-kinase alpha inhibitors (PI3K$ \\alpha $is) have revolutionized breast cancer treatment, but acquired resistance remains a major clinical challenge, with around 40% of patients experiencing progression within 4\u20136 months. Current drug response prediction (DRP) methods typically rely on individual pathways or biomarkers, limiting their ability to capture complex cancer-specific molecular interactions and predict resistance mechanisms. To overcome these limitations, we present AdaSemb, an adaptive, knowledge-driven deep learning framework that uses a multi-protein assembly map to predict responses and resistance to PI3K$ \\alpha $i. AdaSemb comprises two modules: the AdaSemb-PA module incorporates tumor genomic variations into a biological structural neural network, while the AdaSemb-DRP module uses conditional domain adversarial networks to enhance gene\u2013drug distribution generalization. By combining genomic data with drug molecular structures, AdaSemb identifies critical protein combinations linked to drug resistance. In validation with 1244 cancer cell lines and patient-derived xenografts (PDX), AdaSemb outperformed existing DRP models. In a cohort of 116 breast cancer patients from the Cancer Genome Atlas (TCGA), it predicted significantly longer survival for sensitive patients, surpassing traditional biomarkers in precision. Furthermore, we identified seven key assemblages that integrate mutations from 93 genes, which distinguish alpelisib sensitive and resistant cell lines. These results are applicable to breast cancer patient samples and PDX models, demonstrating AdaSemb\u2019s significant clinical potential in personalized treatment and prediction of resistance for breast cancer.<\/jats:p>","DOI":"10.1093\/bib\/bbaf510","type":"journal-article","created":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T11:57:17Z","timestamp":1757678237000},"source":"Crossref","is-referenced-by-count":1,"title":["AdaSemb: an adaptive knowledge-driven deep learning framework integrating cancer protein assemblies for predicting PI3K\u03b1 inhibitor response and resistance"],"prefix":"10.1093","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-4559-1385","authenticated-orcid":false,"given":"Zaiduo","family":"Li","sequence":"first","affiliation":[{"name":"Key Laboratory of Information Fusion Estimation and Detection, Heilongjiang University , Xuefu Road, Harbin 150080 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Dazhi Street, Harbin 150001 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2567-1488","authenticated-orcid":false,"given":"Xiaochuan","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Information Fusion Estimation and Detection, Heilongjiang University , Xuefu Road, Harbin 150080 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9738-2361","authenticated-orcid":false,"given":"Xianyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, Harbin Medical University Cancer Hospital , Haping Road, Harbin 150081 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4008-702X","authenticated-orcid":false,"given":"Tiansong","family":"Yang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, and Traditional Chinese Medicine Informatics Key Laboratory of Heilongjiang Province , Heping Road, 150040, Harbin ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6645-6890","authenticated-orcid":false,"given":"Xiaokun","family":"Li","sequence":"additional","affiliation":[{"name":"School of Computer Science and Technology, Harbin Institute of Technology , West Dazhi Street, Harbin 150001 ,","place":["China"]},{"name":"School of Computer Science and Technology, Heilogjiang University , Xuefu Road, Harbin 150080 ,","place":["China"]},{"name":"Postdoctoral Program of Heilongjiang Hengxun Technology Co., Ltd. , Xuefu Road, Harbin 150090 ,","place":["China"]},{"name":"Shandong Hengxun Technology Co., Ltd. , Miaoling Road, Qingdao 266100 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