MEMCover: integrated analysis of mutual exclusivity and functional network reveals dysregulated pathways across multiple cancer types

Abstract

We introduce a classification of mutual exclusivity into three basic classes: within tissue type exclusivity, across tissue type exclusivity and between tissue type exclusivity. We then combined across-cancer mutual exclusivity with interactions data to uncover pan-cancer dysregulated pathways. Our new method, Mutual Exclusivity Module Cover (MEMCover) not only identified previously known Pan-Cancer dysregulated subnetworks but also novel subnetworks whose across cancer role has not been appreciated well before. In addition, we demonstrate the existence of mutual exclusivity hubs, putatively corresponding to cancer drivers with strong growth advantages. Finally, we show that while mutually exclusive pairs within or across cancer types are predominantly functionally interacting, the pairs in between cancer mutual exclusivity class are more often disconnected in functional networks.