Combinatorial therapies have been recently proposed to improve the efficacy of anticancer treatment. The Synergy Finder R package is a software used to analyze pre-clinical drug combination datasets. Here, we report t...Combinatorial therapies have been recently proposed to improve the efficacy of anticancer treatment. The Synergy Finder R package is a software used to analyze pre-clinical drug combination datasets. Here, we report the major updates to the Synergy Finder R package for improved interpretation and annotation of drug combination screening results. Unlike the existing implementations, the updated Synergy Finder R package includes five main innovations. 1) We extend the mathematical models to higher-order drug combination data analysis and implement dimension reduction techniques for visualizing the synergy landscape. 2) We provide a statistical analysis of drug combination synergy and sensitivity with confidence intervals and P values. 3)We incorporate a synergy barometer to harmonize multiple synergy scoring methods to provide a consensus metric for synergy. 4) We evaluate drug combination synergy and sensitivity to provide an unbiased interpretation of the clinical potential. 5) We enable fast annotation of drugs and cell lines, including their chemical and target information. These annotations will improve the interpretation of the mechanisms of action of drug combinations. To facilitate the use of the R package within the drug discovery community, we also provide a web server at www.s ynergyfinderplus.org as a user-friendly interface to enable a more fexible and versatile analysis of drug combination data.展开更多
基金supported by the European Research Council(ERC) starting grant DrugComb (informatics approaches for the rational selection of personalized cancer drug combinations)(Grant No.716063)the European Commission H2020EOSC-life (providing an open collaborative space for digital biology in Europe)(Grant No.824087)+6 种基金the Academy of Finland grant (Grant No.317680)the Sigrid Juselius Foundation grantfunded by the University of Helsinki through theDoctoral Program of Biomedicine (DPBM)personal grants from K.Albin Johanssons Stiftelse and Biomedicum Helsinki Foundationpersonal grant from K.Albin Johanssons Stiftelsefunded by the University of Helsinki through the Doctoral Program of Integrative Life Science (ILS)personal grant from the Cancer Foundation Finland
文摘Combinatorial therapies have been recently proposed to improve the efficacy of anticancer treatment. The Synergy Finder R package is a software used to analyze pre-clinical drug combination datasets. Here, we report the major updates to the Synergy Finder R package for improved interpretation and annotation of drug combination screening results. Unlike the existing implementations, the updated Synergy Finder R package includes five main innovations. 1) We extend the mathematical models to higher-order drug combination data analysis and implement dimension reduction techniques for visualizing the synergy landscape. 2) We provide a statistical analysis of drug combination synergy and sensitivity with confidence intervals and P values. 3)We incorporate a synergy barometer to harmonize multiple synergy scoring methods to provide a consensus metric for synergy. 4) We evaluate drug combination synergy and sensitivity to provide an unbiased interpretation of the clinical potential. 5) We enable fast annotation of drugs and cell lines, including their chemical and target information. These annotations will improve the interpretation of the mechanisms of action of drug combinations. To facilitate the use of the R package within the drug discovery community, we also provide a web server at www.s ynergyfinderplus.org as a user-friendly interface to enable a more fexible and versatile analysis of drug combination data.
