{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T18:08:17Z","timestamp":1780078097735,"version":"3.54.0"},"reference-count":19,"publisher":"Oxford University Press (OUP)","issue":"23","license":[{"start":{"date-parts":[[2017,8,14]],"date-time":"2017-08-14T00:00:00Z","timestamp":1502668800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004052","name":"King Abdullah University of Science and Technology","doi-asserted-by":"publisher","award":["15KT0084"],"award-info":[{"award-number":["15KT0084"]}],"id":[{"id":"10.13039\/501100004052","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>Drug combination therapy for treatment of cancers and other multifactorial diseases has the potential of increasing the therapeutic effect, while reducing the likelihood of drug resistance. In order to reduce time and cost spent in comprehensive screens, methods are needed which can model additive effects of possible drug combinations.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We here show that the transcriptional response to combinatorial drug treatment at promoters, as measured by single molecule CAGE technology, is accurately described by a linear combination of the responses of the individual drugs at a genome wide scale. We also find that the same linear relationship holds for transcription at enhancer elements. We conclude that the described approach is promising for eliciting the transcriptional response to multidrug treatment at promoters and enhancers in an unbiased genome wide way, which may minimize the need for exhaustive combinatorial screens.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>The CAGE sequence data used in this study is available in the DDBJ Sequence Read Archive (http:\/\/trace.ddbj.nig.ac.jp\/index_e.html), accession number DRP001113.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Supplementary information<\/jats:title>\n                  <jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btx503","type":"journal-article","created":{"date-parts":[[2017,8,9]],"date-time":"2017-08-09T19:13:47Z","timestamp":1502306027000},"page":"3696-3700","source":"Crossref","is-referenced-by-count":7,"title":["Genome-scale regression analysis reveals a linear relationship for promoters and enhancers after combinatorial drug treatment"],"prefix":"10.1093","volume":"33","author":[{"given":"Trisevgeni","family":"Rapakoulia","sequence":"first","affiliation":[{"name":"Computer, Electrical and Mathematical Sciences and Engineering Division (CEMSE), King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia"},{"name":"Computational Bioscience Research Center (CBRC), King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Gao","sequence":"additional","affiliation":[{"name":"Computer, Electrical and Mathematical Sciences and Engineering Division (CEMSE), King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia"},{"name":"Computational Bioscience Research Center (CBRC), King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Huang","sequence":"additional","affiliation":[{"name":"Molecular Network Control Genomics Unit, RIKEN Center for Life Science Technologies, Yokohama, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiel","family":"de Hoon","sequence":"additional","affiliation":[{"name":"RIKEN Center for Life Science Technologies (Division of Genomic Technologies) (CLST (DGT)), Yokohama, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariko","family":"Okada-Hatakeyama","sequence":"additional","affiliation":[{"name":"RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan"},{"name":"Institute for Protein Research, Osaka University, Suita, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harukazu","family":"Suzuki","sequence":"additional","affiliation":[{"name":"RIKEN Center for Life Science Technologies (Division of Genomic Technologies) (CLST (DGT)), Yokohama, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Arner","sequence":"additional","affiliation":[{"name":"Molecular Network Control Genomics Unit, RIKEN Center for Life Science Technologies, Yokohama, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,8,14]]},"reference":[{"key":"2023020207002361300_btx503-B1","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1038\/nature12787","article-title":"An atlas of active enhancers across human cell types and tissues","volume":"507","author":"Andersson","year":"2014","journal-title":"Nature"},{"key":"2023020207002361300_btx503-B2","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1038\/nbt.3052","article-title":"A community computational challenge to predict the activity of pairs of compounds","volume":"32","author":"Bansal","year":"2014","journal-title":"Nat. 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