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Among various obstacles hindering clinical translation, lacking effective methods for multimodal and multisource data integration is becoming a bottleneck.<\/jats:p><jats:p>Here we proposed DeepDRK, a machine learning framework for deciphering drug response through kernel-based data integration. To transfer information among different drugs and cancer types, we trained deep neural networks on more than 20\u00a0000 pan-cancer cell line-anticancer drug pairs. These pairs were characterized by kernel-based similarity matrices integrating multisource and multi-omics data including genomics, transcriptomics, epigenomics, chemical properties of compounds and known drug-target interactions. Applied to benchmark cancer cell line datasets, our model surpassed previous approaches with higher accuracy and better robustness. Then we applied our model on newly established patient-derived cancer cell lines and achieved satisfactory performance with AUC of 0.84 and AUPRC of 0.77. Moreover, DeepDRK was used to predict clinical response of cancer patients. Notably, the prediction of DeepDRK correlated well with clinical outcome of patients and revealed multiple drug repurposing candidates. In sum, DeepDRK provided a computational method to predict drug response of cancer cells from integrating pharmacogenomic datasets, offering an alternative way to prioritize repurposing drugs in precision cancer treatment.<\/jats:p><jats:p>The DeepDRK is freely available via https:\/\/github.com\/wangyc82\/DeepDRK.<\/jats:p>","DOI":"10.1093\/bib\/bbab048","type":"journal-article","created":{"date-parts":[[2021,2,2]],"date-time":"2021-02-02T22:41:47Z","timestamp":1612305707000},"source":"Crossref","is-referenced-by-count":75,"title":["DeepDRK: a deep learning framework for drug repurposing through kernel-based multi-omics integration"],"prefix":"10.1093","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2528-5714","authenticated-orcid":false,"given":"Yongcui","family":"Wang","sequence":"first","affiliation":[{"name":"Key Laboratory of Adaptation and Evolution of Plateau Biota at Northwest Institute of Plateau Biology, Chinese Academy of Sciences, 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