Figure 6.

Pathway crosstalk-based attack analysis identifies critical genes and repurposes licensed medications. (A) Pathway enrichments of the top 1% prioritized target genes. Based on KEGG organismal system pathways that are organized circularly. Each dot represents a pathway, sized by the odd ratio (OR) and colored by the significance level (FDR) calculated using one-sided Fisher’s exact test. (B) Pathway crosstalk identified by integrating target prioritization information with gene interactions (extracted from enriched pathways). Nodes are labelled by gene symbols (priority rank) and highlighted in red if currently targeted by approved drugs in other disease indications. (C) Effect of node removals on the crosstalk. Top: the single-node effect maximized by removing ATK1, the maximum effect of removing another approved drug target in the context of AKT1, and the maximum effect of removing another approved drug target in the context of AKT1 and ESR1. Bottom: node removals are indicated by colored circles.