SynergyFinder 3.0: an interactive analysis and consensus interpretation of multi-drug synergies across multiple samples

Abstract

SynergyFinder (https://synergyfinder.fimm.fi) is a free web-application for interactive analysis and visualization of multi-drug combination response data. Since its first release in 2017, SynergyFinder has become a popular tool for multi-dose combination data analytics, partly because the development of its functionality and graphical interface has been driven by a diverse user community, including both chemical biologists and computational scientists. Here, we describe the latest upgrade of this community-effort, SynergyFinder release 3.0, introducing a number of novel features that support interactive multi-sample analysis of combination synergy, a novel consensus synergy score that combines multiple synergy scoring models, and an improved outlier detection functionality that eliminates false positive results, along with many other post-analysis options such as weighting of synergy by drug concentrations and distinguishing between different modes of synergy (potency and efficacy). Based on user requests, several additional improvements were also implemented, including new data visualizations and export options for multi-drug combinations. With these improvements, SynergyFinder 3.0 supports robust identification of consistent combinatorial synergies for multi-drug combinatorial discovery and clinical translation.

Graphical Abstract

SynergyFinder 3.0: an interactive analysis and consensus interpretation of multi-drug synergies across multiple samples.

Figure 1.

Novel features implemented in the SynergyFinder version 3.0 include (A) multi-sample analysis with interactive visualization of combination effects across the samples, (B) Bliss/Loewe consensus scoring to eliminate false positive synergy results (in the example case, user-selected HSA model identifies moderate-to-strong synergy, whereas Bliss/Loewe consensus suggests a strong antagonism, indicating low-confidence HSA synergy), (C) multiple post-analysis options, such as distinguishing between different modes of synergy (potency and efficacy), and prioritizing of combinations that show maximal synergy at lower doses (the dotted box). (D) An example of how SynergyFinder highlights combinations that show synergy at lower dose windows by weighting synergy at each dose level according to the proportion of response values of single-agents at these doses (see text for details).