An Algorithm to Mine Therapeutic Motifs for Cancer From Networks of Genetic Interactions.

Abstract

Study of pairwise genetic interactions, such as mutually exclusive mutations, has led to understanding of underlying mechanisms in cancer. Investigation of various combinatorial motifs within networks of such interactions can lead to deeper insights into its mutational landscape and inform therapy development. One such motif called the Between-Pathway Model (BPM) represents redundant or compensatory pathways that can be therapeutically exploited. Finding such BPM motifs is challenging since most formulations require solving variants of the NP-complete maximum weight bipartite subgraph problem. In this paper we design an algorithm based on Integer Linear Programming (ILP) to solve this problem. In our experiments, our approach outperforms the best previous method to mine BPM motifs. Further, our ILP-based approach allows us to easily model additional application-specific constraints. We illustrate this advantage through a new application of BPM motifs that can potentially aid in finding combination therapies to combat cancer.