APC and colorectal cancer: For the majority of the evaluable mutations in colorectal cancer (Supplementary Fig. 2b), enrichment analysis using gene set enrichment analysis (GSEA)26 revealed that MiSL candidates were preferentially ranked higher by mutation-specific essentiality in colorectal cancer (Fig. 2b–d, Supplementary Fig. 2c–e) and included statistically significant results for APC (normalized enrichment score (NES)=1.55, P value=0.003), KRAS (NES=1.48, P value=0.04) and PIK3CA (NES=1.35, P value=0.03).