{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T06:42:53Z","timestamp":1757313773833,"version":"3.41.2"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T00:00:00Z","timestamp":1732060800000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program","doi-asserted-by":"publisher","award":["2023YFC3502604"],"award-info":[{"award-number":["2023YFC3502604"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82204941","82174533","82374302","U23B2062"],"award-info":[{"award-number":["82204941","82174533","82374302","U23B2062"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004826","name":"Natural Science Foundation of Beijing","doi-asserted-by":"publisher","award":["L232033"],"award-info":[{"award-number":["L232033"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>Drug repositioning (DR), identifying novel indications for approved drugs, is a cost-effective strategy in drug discovery. Despite numerous proposed DR models, integrating network-based features, differential gene expression, and chemical structures for high-performance DR remains challenging.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We propose a comprehensive deep pretraining and fine-tuning framework for DR, termed DrugRepPT. Initially, we design a graph pretraining module employing model-augmented contrastive learning on a vast drug\u2013disease heterogeneous graph to capture nuanced interactions and expression perturbations after intervention. Subsequently, we introduce a fine-tuning module leveraging a graph residual-like convolution network to elucidate intricate interactions between diseases and drugs. Moreover, a Bayesian multiloss approach is introduced to balance the existence and effectiveness of drug treatment effectively. Extensive experiments showcase the efficacy of our framework, with DrugRepPT exhibiting remarkable performance improvements compared to SOTA (state of the arts) baseline methods (improvement 106.13% on Hit@1 and 54.45% on mean reciprocal rank). The reliability of predicted results is further validated through two case studies, i.e. gastritis and fatty liver, via literature validation, network medicine analysis, and docking screening.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>The code and results are available at https:\/\/github.com\/2020MEAI\/DrugRepPT.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btae692","type":"journal-article","created":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T08:39:22Z","timestamp":1732091962000},"source":"Crossref","is-referenced-by-count":1,"title":["DrugRepPT: a deep pretraining and fine-tuning framework for drug repositioning based on drug\u2019s expression perturbation and treatment effectiveness"],"prefix":"10.1093","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1258-4130","authenticated-orcid":false,"given":"Shuyue","family":"Fan","sequence":"first","affiliation":[{"name":"Department of Artificial Intelligence, Beijing Key Lab of Traffic Data Analysis and Mining, School of Computer Science & Technology, Beijing Jiaotong University , Beijing 100044,","place":["China"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0736-4512","authenticated-orcid":false,"given":"Kuo","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Artificial Intelligence, Beijing Key Lab of Traffic Data Analysis and Mining, School of Computer Science & Technology, Beijing Jiaotong University , Beijing 100044,","place":["China"]}]},{"given":"Kezhi","family":"Lu","sequence":"additional","affiliation":[{"name":"Faculty of Engineering and IT, Australian AI Institute, University of Technology Sydney , Sydney, NSW 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100044,","place":["China"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8709-9167","authenticated-orcid":false,"given":"Shao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Automation, MOE Key Laboratory of Bioinformatics\/Bioinformatics Division, BNRIST, Institute for TCM-X, Tsinghua University , Beijing 100084,","place":["China"]}]},{"given":"Jianyang","family":"Zeng","sequence":"additional","affiliation":[{"name":"School of Engineering, Westlake University , Hangzhou 310030,","place":["China"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4713-3594","authenticated-orcid":false,"given":"Xuezhong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Artificial Intelligence, Beijing Key Lab of Traffic Data Analysis and Mining, School of Computer Science & Technology, Beijing Jiaotong University , Beijing 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