Fig. 1: The Combocat platform for dense drug combination screens.

a Practical representation of drug synergy, where the combined effect of two drugs exceeds the expected effect (“E”) based on models like additivity or Bliss independence. b Examples of traditional high-throughput screens employing small (e.g., 3 × 3), sparse, or asymmetric (e.g., 2 × 7) matrix formats, which limit dose density. c Combocat’s streamlined approach for dense and reproducible drug combination screening. The 384-well plate format contains Drugs 1 and 2 (represented by upper and lower triangles, respectively), with concentrations shown ranging from low (blue) to high (red). Three replicate 10 × 10 combination matrices are generated for each drug pair, along with three replicates of each single-agent dose-response. Twelve replicates each of cell death (orange) and vehicle (yellow) controls are included for normalization. d Overview of the Combocat analytical pipeline. Raw data are mapped to corresponding combination matrices and subsequently normalized to percentage cell death using controls. Synergy is then quantified using the Bliss independence model. Results are summarized across the screen to identify top synergistic interactions.