{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,22]],"date-time":"2025-02-22T00:45:49Z","timestamp":1740185149124,"version":"3.37.3"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"19","license":[{"start":{"date-parts":[[2019,3,9]],"date-time":"2019-03-09T00:00:00Z","timestamp":1552089600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100004917","name":"Cancer Prevention Research Institute of Texas","doi-asserted-by":"publisher","award":["RP130397"],"award-info":[{"award-number":["RP130397"]}],"id":[{"id":"10.13039\/100004917","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001538","name":"Mary K. Chapman Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001538","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000880","name":"Michael & Susan Dell Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000880","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100007313","name":"MD Anderson Cancer Center","doi-asserted-by":"publisher","award":["P30 CA016672"],"award-info":[{"award-number":["P30 CA016672"]}],"id":[{"id":"10.13039\/100007313","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Bioinformatics Shared Resource"},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>The concept of synergy between two agents, over a century old, is important to the fields of biology, chemistry, pharmacology and medicine. A key step in drug combination analysis is the selection of an additivity model to identify combination effects including synergy, additivity and antagonism. Existing methods for identifying and interpreting those combination effects have limitations.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We present here a computational framework, termed response envelope analysis (REA), that makes use of 3D response surfaces formed by generalized Loewe Additivity and Bliss Independence models of interaction to evaluate drug combination effects. Because the two models imply two extreme limits of drug interaction (mutually exclusive and mutually non-exclusive), a response envelope defined by them provides a quantitatively stringent additivity model for identifying combination effects without knowing the inhibition mechanism. As a demonstration, we apply REA to representative published data from large screens of anticancer and antibiotic combinations. We show that REA is more accurate than existing methods and provides more consistent results in the context of cross-experiment evaluation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>The open-source software package associated with REA is available at: https:\/\/github.com\/4dsoftware\/rea.<\/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\/btz091","type":"journal-article","created":{"date-parts":[[2019,3,7]],"date-time":"2019-03-07T20:40:01Z","timestamp":1551991201000},"page":"3761-3770","source":"Crossref","is-referenced-by-count":5,"title":["Response envelope analysis for quantitative evaluation of drug combinations"],"prefix":"10.1093","volume":"35","author":[{"given":"Di","family":"Du","sequence":"first","affiliation":[{"name":"Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center , Houston, TX, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chia-Hua","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center , Houston, TX, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yumeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center , Houston, TX, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pan","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center , Houston, TX, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wai Kin","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center , Houston, TX, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yulun","family":"Chiu","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center , Houston, TX, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center , Houston, TX, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center , Houston, TX, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John N","family":"Weinstein","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center , Houston, TX, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip L","family":"Lorenzi","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center , Houston, TX, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,3,9]]},"reference":[{"key":"2023013108145281600_btz091-B1","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1038\/nbt.2284","article-title":"Combinatorial drug therapy for cancer in the post-genomic era","volume":"30","author":"Al-Lazikani","year":"2012","journal-title":"Nat. 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