Fig. 2. Synergy is rare and highly context-dependent.

a, Overlap of synergy identified at two anchor concentrations. n = 5,541 synergistic combination-cell line pairs. b, Synergy calls by ΔIC₅₀ and ΔE_max are complementary. n = 9,402 synergistic measurements. c, Navitoclax combination partners and tissue-specific enrichment in synergy (hypergeometric test). Enriched navitoclax partners (P ≤ 0.005, FDR ≤ 5%) are labelled. d, Combinations of navitoclax with AURK inhibitors are frequently synergistic in breast cancer cell lines, with exception of HER2 cells. Binary synergy for navitoclax (anchor) paired with three AURK inhibitors with indicated specificity across PAM50 subtypes. e, Synergy rates for 1,736 combinations of two targeted drugs by minimum (min.) network distance between drug targets. Two-sided Student’s t-test. f, Twenty-four unique target pathway pairs enriched in synergy in at least one tissue (136 unique pairs tested; hypergeometric test, P ≤ 0.005, FDR ≤ 5%). Red denotes pathway pairs that are enriched in all three tissues.