Fig. 5: Synthetic chemogenetic interactions.

MELJUSO cells were cultured in the presence of MEK inhibitor selumetinib and screened for chemogenetic interactions (A) DrugZ scores of single gene knockouts. Selected genes in the MAPK and Hippo pathways highlighted. Red, synergistic; blue, suppressor. B Selected GSEA results and significance tests (one-sided weighted Kolmogorov–Smirnov statistic) for gene sets conferring sensitivity (ERK signaling) or resistance (Hippo signaling) to MEKi. C Comparing DrugZ scores of paralogs (x-axis) vs. the most extreme Z score of the single gene knockout (y-axis) shows that most pairwise perturbagens yield similar phenotype as singletons. Outliers in red (synergistic) or blue (suppressor). D Synergistic and suppressor paralog knockouts from C. Asterisk indicates functional buffering in the Hippo pathway, masking phenotype in monogenic knockout screens.