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000 | 14219naa a2204573 4500 | |
001 | oai:prod.swepub.kib.ki.se:141113030 | |
003 | SwePub | |
008 | 240701s2019 | |||||||||||000 ||eng| | |
024 | 7 | a http://kipublications.ki.se/Default.aspx?queryparsed=id:1411130302 URI |
024 | 7 | a https://doi.org/10.1038/s41467-019-09799-22 DOI |
040 | a (SwePub)ki | |
041 | a engb eng | |
042 | 9 SwePub | |
072 | 7 | a ref2 swepub-contenttype |
072 | 7 | a art2 swepub-publicationtype |
100 | 1 | a Menden, MP4 aut |
245 | 1 0 | a Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen |
264 | c 2019-06-17 | |
264 | 1 | b Springer Science and Business Media LLC,c 2019 |
520 | a The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells. | |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Farmaceutiska vetenskaper0 (SwePub)301012 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Pharmaceutical Sciences0 (SwePub)301012 hsv//eng |
650 | 7 | a NATURVETENSKAPx Data- och informationsvetenskapx Bioinformatik0 (SwePub)102032 hsv//swe |
650 | 7 | a NATURAL SCIENCESx Computer and Information Sciencesx Bioinformatics0 (SwePub)102032 hsv//eng |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Cancer och onkologi0 (SwePub)302032 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Cancer and Oncology0 (SwePub)302032 hsv//eng |
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710 | 2 | a Karolinska Institutet4 org |
773 | 0 | t Nature communicationsd : Springer Science and Business Media LLCg 10:1, s. 2674-q 10:1<2674-x 2041-1723 |
856 | 4 | u https://www.nature.com/articles/s41467-019-09799-2.pdf |
856 | 4 8 | u http://kipublications.ki.se/Default.aspx?queryparsed=id:141113030 |
856 | 4 8 | u https://doi.org/10.1038/s41467-019-09799-2 |
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