Illustration of DNA wrapped around histone proteins. Source: Adapted from the website of the National Cancer Institute.
Aberrant DNA methylation is an important mechanism that contributes to oncogenesis. Yet, few algorithms exist that exploit this vast dataset to identify hypo- and hyper-methylated genes in cancer. We developed a novel computational algorithm called MethylMix to identify differentially methylated genes that are also predictive of transcription. We apply MethylMix to twelve individual cancer sites, and additionally combine all cancer sites in a pancancer analysis. We discover pancancer hypo- and hyper-methylated genes and identify novel methylation-driven subgroups with clinical implications. MethylMix analysis on combined cancer sites reveals ten pancancer clusters reflecting new similarities across malignantly transformed tissues. (Publication Abstract)