Statistical Methods Pipeline.

A) 549 genes with a total of 33507 pan-cancer mutations are run through our multiscale clustering algorithm resulting in 1295 clusters. B) Clusters are assigned to 4471 tumors samples across 23 tumor types creating a binary feature matrix. A tumor sample is said to be positive for a cluster if there is any non-synonymous mutation in the tumor and the cluster. C) The binary feature matrices are statistically compared to 2194 gene expression features separately for each cancer type using the Kruskal-Wallis Test. D) The pairwise P-values from the Kruskal-Wallis tests are combined globally and on the pathway level using the Empirical Brown’s Method across 172 Pathways. E) This resulted in 546810 association P-values.