Fig. 5.

Drugs falling into Class IV are synergistic with drugs targeting the PI3K pathway. a, b GR values for individual drug combinations a or over a range of combinations b and excess over Bliss scores (bottom) for 72 h exposure of BT-20 cells to combinations of the PI3K inhibitor alpelisib with either the ErbB inhibitors lapatinib (left) or neratinib (middle) or with the MEK inhibitor trametinib (right). Histograms in a show the mean of three biological repeats and error bars indicate the standard error of the mean; p-value is based on a t-test. Heatmaps in b show data from one out of three biological replicates. c Network of significant perturbations (SCS > 1.3) for BT-20 cells. Each node is a unique perturbation (combination of drug, time point, and concentration) and edges are drawn between perturbations with a cosine distance in the lower 5-percentile. Nodes are colored by drugs targeting receptors, the MAPK proteins or components of the PI3K/AKT pathways (left) or the GR value of the response (right). Node size reflects drug concentration. d Schematic of the converging effect of drug treatments and illustration of drug equivalence classes in BT-20