{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T21:18:42Z","timestamp":1783459122333,"version":"3.55.0"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"vor","delay-in-days":2,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Health Data Research UK-The Alan Turing Institute Wellcome","award":["218529\/Z\/19\/Z"],"award-info":[{"award-number":["218529\/Z\/19\/Z"]}]},{"name":"Wellcome Cambridge Trust Scholarship"},{"name":"UKRI-EPSRC","award":["EP\/Y028805\/1"],"award-info":[{"award-number":["EP\/Y028805\/1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Many cancer monotherapies demonstrate limited clinical efficacy, making combination therapies a relevant treatment strategy. The extensive number of potential drug combinations and context-specific response profiles complicates the prediction of drug combination responses. Existing computational models are typically trained to predict a single aggregated synergy score, which summarises drug responses across different dosage combinations, such as Bliss or Loewe scores. This oversimplification of the drug-response surface leads to high prediction uncertainty and limited actionability, as these models fail to distinguish between potency and efficacy. We introduce DeepSynBa, an actionable model that predicts the complete dose-response matrix of drug pairs instead of relying on an aggregated synergy score. This is achieved by predicting parameters describing the response surface as an intermediate layer in the model. Evaluated on the NCI-ALMANAC and the O\u2019Neil datasets, DeepSynBa outperforms the state-of-the-art methods in the dose-response matrix prediction task across most evaluation scenarios, including testing on novel drug combinations, cell lines, and drugs, across nine different tissue types. We also show that DeepSynBa yields reliable synergy score predictions. More importantly, DeepSynBa can predict drug combination responses across different dosages for untested combinations. The intermediate dose-response parameter layer enables the separation of efficacy from potency, informing the selection of dosage ranges that optimise efficacy while limiting off-target toxicity in experimental screens. The predictive capability and the downstream actionability make DeepSynBa a powerful tool for advancing drug combination research beyond the limitations of the current approaches. The code and the dataset for DeepSynBa are available at https:\/\/github.com\/hikuru\/DeepSynBa.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btag416","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T11:18:31Z","timestamp":1781695111000},"source":"Crossref","is-referenced-by-count":0,"title":["DeepSynBa: actionable drug combination prediction with complete dose-response profiles"],"prefix":"10.1093","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4356-8846","authenticated-orcid":false,"given":"Halil Ibrahim","family":"Kuru","sequence":"first","affiliation":[{"name":"Department of Computer Engineering, Bilkent University , Ankara,","place":["Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoting","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Computer Science and Technology, University of Cambridge , Cambridge,","place":["United Kingdom"]},{"name":"Health Data Research UK , 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