{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T10:52:42Z","timestamp":1769856762249,"version":"3.49.0"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"Supplement_1","license":[{"start":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T00:00:00Z","timestamp":1688083200000},"content-version":"vor","delay-in-days":29,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["62272490"],"award-info":[{"award-number":["62272490"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["61972422"],"award-info":[{"award-number":["61972422"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,6,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>The coronavirus disease 2019 (COVID-19) remains a global public health emergency. Although people, especially those with underlying health conditions, could benefit from several approved COVID-19 therapeutics, the development of effective antiviral COVID-19 drugs is still a very urgent problem. Accurate and robust drug response prediction to a new chemical compound is critical for discovering safe and effective COVID-19 therapeutics.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In this study, we propose DeepCoVDR, a novel COVID-19 drug response prediction method based on deep transfer learning with graph transformer and cross-attention. First, we adopt a graph transformer and feed-forward neural network to mine the drug and cell line information. Then, we use a cross-attention module that calculates the interaction between the drug and cell line. After that, DeepCoVDR combines drug and cell line representation and their interaction features to predict drug response. To solve the problem of SARS-CoV-2 data scarcity, we apply transfer learning and use the SARS-CoV-2 dataset to fine-tune the model pretrained on the cancer dataset. The experiments of regression and classification show that DeepCoVDR outperforms baseline methods. We also evaluate DeepCoVDR on the cancer dataset, and the results indicate that our approach has high performance compared with other state-of-the-art methods. Moreover, we use DeepCoVDR to predict COVID-19 drugs from FDA-approved drugs and demonstrate the effectiveness of DeepCoVDR in identifying novel COVID-19 drugs.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>https:\/\/github.com\/Hhhzj-7\/DeepCoVDR.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btad244","type":"journal-article","created":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T08:18:17Z","timestamp":1688113097000},"page":"i475-i483","source":"Crossref","is-referenced-by-count":18,"title":["DeepCoVDR: deep transfer learning with graph transformer and cross-attention for predicting COVID-19 drug response"],"prefix":"10.1093","volume":"39","author":[{"given":"Zhijian","family":"Huang","sequence":"first","affiliation":[{"name":"School of Computer Science and Engineering, Central South University , Changsha 410083, China"}]},{"given":"Pan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory of Clinical Epidemiology, Xiangya School of Public Health, Central South University , Changsha 410083, China"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3340-2431","authenticated-orcid":false,"given":"Lei","family":"Deng","sequence":"additional","affiliation":[{"name":"School of Computer Science and Engineering, Central South University , Changsha 410083, China"}]}],"member":"286","published-online":{"date-parts":[[2023,6,30]]},"reference":[{"key":"2023063008155787800_btad244-B1","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.1056\/NEJMp1500848","article-title":"The $2.6 billion pill-methodologic and policy considerations","volume":"372","author":"Avorn","year":"2015","journal-title":"N Engl J Med"},{"key":"2023063008155787800_btad244-B2","first-page":"1","volume-title":"Noise Reduction in Speech Processing","author":"Benesty","year":"2009"},{"key":"2023063008155787800_btad244-B3","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1023\/A:1010933404324","article-title":"Random forests","volume":"45","author":"Breiman","year":"2001","journal-title":"Mach Learn"},{"key":"2023063008155787800_btad244-B4","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1056\/NEJMoa2001282","article-title":"A trial of lopinavir\u2013ritonavir in adults hospitalized with severe COVID-19","volume":"382","author":"Cao","year":"2020","journal-title":"N Engl J Med"},{"key":"2023063008155787800_btad244-B5","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1111\/bph.13798","article-title":"Drug repurposing from the perspective of pharmaceutical companies","volume":"175","author":"Cha","year":"2018","journal-title":"Br J Pharmacol"},{"key":"2023063008155787800_btad244-B6","first-page":"1","article-title":"Cancer drug response profile scan (CDRscan): a deep learning model that predicts drug effectiveness from cancer genomic signature","volume":"8","author":"Chang","year":"2018","journal-title":"Sci Rep"},{"key":"2023063008155787800_btad244-B7","first-page":"785","author":"Chen","year":"2016"},{"key":"2023063008155787800_btad244-B8","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1038\/s42255-021-00479-4","article-title":"Pharmacological inhibition of fatty acid synthesis blocks SARS-CoV-2 replication","volume":"3","author":"Chu","year":"2021","journal-title":"Nat Metab"},{"key":"2023063008155787800_btad244-B9","first-page":"65","article-title":"Pharmacogenetics: a general review on progress to date","volume":"124","author":"Daly","year":"2017","journal-title":"Br Med Bull"},{"key":"2023063008155787800_btad244-B10","doi-asserted-by":"crossref","first-page":"107945","DOI":"10.1016\/j.asoc.2021.107945","article-title":"A deep learning ensemble approach to prioritize antiviral drugs against novel coronavirus SARS-CoV-2 for covid-19 drug repurposing","volume":"113","author":"Deepthi","year":"2021","journal-title":"Appl Soft Comput"},{"key":"2023063008155787800_btad244-B11","first-page":"1","volume-title":"International Workshop on Multiple Classifier Systems","author":"Dietterich","year":"2000"},{"key":"2023063008155787800_btad244-B12","first-page":"1263","volume-title":"International Conference on Machine Learning","author":"Gilmer","year":"2017"},{"key":"2023063008155787800_btad244-B13","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1038\/s41586-020-2286-9","article-title":"A SARS-CoV-2 protein interaction map reveals targets for drug repurposing","volume":"583","author":"Gordon","year":"2020","journal-title":"Nature"},{"key":"2023063008155787800_btad244-B14","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.1056\/NEJMoa2002032","article-title":"Clinical characteristics of coronavirus disease 2019 in China","volume":"382","author":"Guan","year":"2020","journal-title":"N Eng J Med"},{"key":"2023063008155787800_btad244-B15","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1056\/NEJMoa2118542","article-title":"Oral nirmatrelvir for high-risk, nonhospitalized adults with covid-19","volume":"386","author":"Hammond","year":"2022","journal-title":"N Eng J Med"},{"key":"2023063008155787800_btad244-B16","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1109\/5254.708428","article-title":"Support vector machines","volume":"13","author":"Hearst","year":"1998","journal-title":"IEEE Intell Syst Their Appl"},{"key":"2023063008155787800_btad244-B17","doi-asserted-by":"crossref","first-page":"e2024302118","DOI":"10.1073\/pnas.2024302118","article-title":"Drugs repurposed for covid-19 by virtual screening of 6,218 drugs and cell-based assay","volume":"118","author":"Jang","year":"2021","journal-title":"Proc Natl Acad Sci USA"},{"key":"2023063008155787800_btad244-B18","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1056\/NEJMoa2116044","article-title":"Molnupiravir for oral treatment of covid-19 in nonhospitalized patients","volume":"386","author":"Jayk Bernal","year":"2022","journal-title":"N Eng J Med"},{"key":"2023063008155787800_btad244-B19","doi-asserted-by":"crossref","first-page":"e00819\u201320","DOI":"10.1128\/AAC.00819-20","article-title":"Identification of antiviral drug candidates against SARS-CoV-2 from fda-approved drugs","volume":"64","author":"Jeon","year":"2020","journal-title":"Antimicrob Agents Chemother"},{"key":"2023063008155787800_btad244-B20","doi-asserted-by":"crossref","first-page":"bbac100","DOI":"10.1093\/bib\/bbac100","article-title":"Deeptta: a transformer-based model for predicting cancer drug response","volume":"23","author":"Jiang","year":"2022","journal-title":"Brief Bioinf"},{"key":"2023063008155787800_btad244-B21","doi-asserted-by":"crossref","first-page":"D1102","DOI":"10.1093\/nar\/gky1033","article-title":"Pubchem 2019 update: improved access to chemical data","volume":"47","author":"Kim","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"2023063008155787800_btad244-B22","author":"Kipf","year":"2017"},{"key":"2023063008155787800_btad244-B23","doi-asserted-by":"crossref","first-page":"2070","DOI":"10.1158\/0008-5472.CAN-03-3645","article-title":"Orlistat is a novel inhibitor of fatty acid synthase with antitumor activity","volume":"64","author":"Kridel","year":"2004","journal-title":"Cancer Res"},{"key":"2023063008155787800_btad244-B24","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1023\/A:1027221424359","article-title":"Similarity and dissimilarity: a medicinal chemist\u2019s view","volume":"9","author":"Kubinyi","year":"1998","journal-title":"Perspect Drug Disc Des"},{"key":"2023063008155787800_btad244-B25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12859-019-2910-6","article-title":"Improving prediction of phenotypic drug response on cancer cell lines using deep convolutional network","volume":"20","author":"Liu","year":"2019","journal-title":"BMC Bioinf"},{"key":"2023063008155787800_btad244-B26","doi-asserted-by":"crossref","first-page":"i911","DOI":"10.1093\/bioinformatics\/btaa822","article-title":"Deepcdr: a hybrid graph convolutional network for predicting cancer drug response","volume":"36","author":"Liu","year":"2020","journal-title":"Bioinformatics"},{"key":"2023063008155787800_btad244-B27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12985-020-01457-0","article-title":"Analysis of the efficacy of HIV protease inhibitors against SARS-CoV-2\u015b main protease","volume":"17","author":"Mahdi","year":"2020","journal-title":"Virol J"},{"key":"2023063008155787800_btad244-B28","doi-asserted-by":"crossref","first-page":"107135","DOI":"10.1016\/j.asoc.2021.107135","article-title":"Drug repositioning based on similarity constrained probabilistic matrix factorization: covid-19 as a case study","volume":"103","author":"Meng","year":"2021","journal-title":"Appl Soft Comput"},{"key":"2023063008155787800_btad244-B29","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1021\/c160017a018","article-title":"The generation of a unique machine description for chemical structures-a technique developed at chemical abstracts service","volume":"5","author":"Morgan","year":"1965","journal-title":"J Chem Doc"},{"key":"2023063008155787800_btad244-B30","first-page":"1","article-title":"Spearman correlation coefficients, differences between","volume":"12","author":"Myers","journal-title":"Encycl Statist Sci 2004;"},{"key":"2023063008155787800_btad244-B31","author":"Nair","year":"2010"},{"key":"2023063008155787800_btad244-B32","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1126\/science.abl4784","article-title":"An oral SARS-CoV-2 mpro inhibitor clinical candidate for the treatment of covid-19","volume":"374","author":"Owen","year":"2021","journal-title":"Science"},{"key":"2023063008155787800_btad244-B33","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1109\/TKDE.2009.191","article-title":"A survey on transfer learning","volume":"22","author":"Pan","year":"2010","journal-title":"IEEE Trans Knowl Data Eng"},{"key":"2023063008155787800_btad244-B34","first-page":"2825","article-title":"Scikit-learn: machine learning in python","volume":"12","author":"Pedregosa","year":"2011","journal-title":"J Mach Learn Res"},{"key":"2023063008155787800_btad244-B35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-021-83737-5","article-title":"Prioritizing antiviral drugs against SARS-CoV-2 by integrating viral complete genome sequences and drug chemical structures","volume":"11","author":"Peng","year":"2021","journal-title":"Sci Rep"},{"key":"2023063008155787800_btad244-B36","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1016\/j.ijbiomac.2020.12.020","article-title":"Assessment of antiviral potencies of cannabinoids against SARS-CoV-2 using computational and in vitro approaches","volume":"168","author":"Raj","year":"2021","journal-title":"Int J Biol Macromol"},{"key":"2023063008155787800_btad244-B37","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1038\/s41586-020-2577-1","article-title":"Discovery of SARS-CoV-2 antiviral drugs through large-scale compound repurposing","volume":"586","author":"Riva","year":"2020","journal-title":"Nature"},{"key":"2023063008155787800_btad244-B38","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.omtm.2020.11.002","article-title":"Enhanced expression of immune checkpoint receptors during SARS-CoV-2 viral infection","volume":"20","author":"Sharif-Askari","year":"2021","journal-title":"Mol Ther Methods Clin Dev"},{"key":"2023063008155787800_btad244-B39","doi-asserted-by":"crossref","first-page":"i501","DOI":"10.1093\/bioinformatics\/btz318","article-title":"Moli: multi-omics late integration with deep neural networks for drug response prediction","volume":"35","author":"Sharifi-Noghabi","year":"2019","journal-title":"Bioinformatics"},{"key":"2023063008155787800_btad244-B40","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1038\/nmeth.4365","article-title":"Probes & drugs portal: an interactive, open data resource for chemical biology","volume":"14","author":"Skuta","year":"2017","journal-title":"Nat Methods"},{"key":"2023063008155787800_btad244-B41","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1001\/jama.2020.16349","article-title":"Effect of remdesivir vs standard care on clinical status at 11 days in patients with moderate covid-19: a randomized clinical trial","volume":"324","author":"Spinner","year":"2020","journal-title":"JAMA"},{"key":"2023063008155787800_btad244-B42","article-title":"Visualizing data using t-sne","author":"Van der Maaten","journal-title":"J Mach Learn Res"},{"key":"2023063008155787800_btad244-B43","first-page":"5998","article-title":"Attention is all you need","volume":"30","author":"Vaswani","year":"2017","journal-title":"Adv Neural Inf Process Syst"},{"key":"2023063008155787800_btad244-B44","author":"Veli\u010dkovi\u0107"},{"key":"2023063008155787800_btad244-B45","doi-asserted-by":"crossref","first-page":"bbab211","DOI":"10.1093\/bib\/bbab211","article-title":"A transferable deep learning approach to fast screen potential antiviral drugs against SARS-CoV-2","volume":"22","author":"Wang","year":"2021","journal-title":"Brief Bioinf"},{"key":"2023063008155787800_btad244-B46","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.virol.2021.09.009","article-title":"Viral polymerase binding and broad-spectrum antiviral activity of molnupiravir against human seasonal coronaviruses","volume":"564","author":"Wang","year":"2021","journal-title":"Virology"},{"key":"2023063008155787800_btad244-B47","first-page":"10941","author":"Wei","year":"2020"},{"key":"2023063008155787800_btad244-B48","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1002\/minf.201400024","article-title":"The calculation of molecular structural similarity: principles and practice","volume":"33","author":"Willett","year":"2014","journal-title":"Mol Inform"},{"key":"2023063008155787800_btad244-B49","doi-asserted-by":"crossref","first-page":"3370","DOI":"10.1021\/acs.jcim.9b00237","article-title":"Analyzing learned molecular representations for property prediction","volume":"59","author":"Yang","year":"2019","journal-title":"J Chem Inf Model"},{"key":"2023063008155787800_btad244-B50","doi-asserted-by":"crossref","first-page":"D955","DOI":"10.1093\/nar\/gks1111","article-title":"Genomics of drug sensitivity in cancer (GDSC): a resource for therapeutic biomarker discovery in cancer cells","volume":"41","author":"Yang","year":"2013","journal-title":"Nucleic Acids Res"},{"key":"2023063008155787800_btad244-B51","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1126\/science.abc1560","article-title":"Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir","volume":"368","author":"Yin","year":"2020","journal-title":"Science"},{"key":"2023063008155787800_btad244-B52","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41597-022-01532-x","article-title":"Cytopathic SARS-CoV-2 screening on vero-e6 cells in a large-scale repurposing effort","volume":"9","author":"Zaliani","year":"2022","journal-title":"Sci Data"},{"key":"2023063008155787800_btad244-B53","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41421-020-0153-3","article-title":"Network-based drug repurposing for novel coronavirus 2019-NCOV SARS-CoV-2","volume":"6","author":"Zhou","year":"2020","journal-title":"Cell Discov"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/39\/Supplement_1\/i475\/50741651\/btad244.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/39\/Supplement_1\/i475\/50741651\/btad244.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T08:19:23Z","timestamp":1688113163000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/39\/Supplement_1\/i475\/7210469"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,1]]},"references-count":53,"journal-issue":{"issue":"Supplement_1","published-print":{"date-parts":[[2023,6,30]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btad244","relation":{},"ISSN":["1367-4803","1367-4811"],"issn-type":[{"value":"1367-4803","type":"print"},{"value":"1367-4811","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,6,1]]},"published":{"date-parts":[[2023,6,1]]}}}