SynergyFinder Plus: towards a better interpretation and annotation of drug combination screening datasets

Combinatorial therapies have recently been proposed for improving anticancer treatment efficacy. The SynergyFinder R package is a software tool to analyse pre-clinical drug combination datasets. We report the major updates to the R package to improve the interpretation and annotation of drug combination screening results. Compared to the existing implementations, the novelty of the updated SynergyFinder R package consists of 1) extending to higher-order drug combination data analysis and the implementation of dimension reduction techniques for visualizing the synergy landscape for an unlimited number of drugs in a combination; 2) statistical analysis of drug combination synergy and sensitivity with confidence intervals and p-values; 3) incorporating a synergy barometer to harmonize multiple synergy scoring methods to provide a consensus metric of synergy; and 4) incorporating the evaluation of drug combination synergy and sensitivity simultaneously to provide an unbiased interpretation of the clinical potential. Furthermore, we enabled fast annotation for drugs and cell lines that are tested in an experiment, including their chemical information, targets and signalling network information. These annotations shall 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.synergyfinderplus.org that provides a user-friendly interface to enable a more flexible and versatile analysis of drug combination data.