Oncogenetic network estimation with disjunctive Bayesian networks

Abstract

Motivation: Cancer is the process of accumulating genetic alterations that confer selective advantages to tumor cells. The order in which aberrations occur is not arbitrary, and inferring the order of events is challenging due to the lack of longitudinal samples from tumors. Moreover, a network model of oncogenesis should capture biological facts such as distinct progression trajectories of cancer subtypes and patterns of mutual exclusivity of alterations in the same pathways. In this paper, we present the disjunctive Bayesian network (DBN), a novel oncogenetic model with a phylogenetic interpretation. DBN is expressive enough to capture cancer subtypes' trajectories and mutually exclusive relations between alterations from unstratified data. Results: In cases where the number of studied alterations is small ((Formula presented.)), we provide an efficient dynamic programming implementation of an exact structure learning method that finds a best DBN in the superexponential search space of networks. In rare cases that the number of alterations is large, we provided an efficient genetic algorithm in our software package, OncoBN. Through numerous synthetic and real data experiments, we show OncoBN's ability in inferring ground truth networks and recovering biologically meaningful progression networks. Availability: OncoBN is implemented in R and is available at https://github.com/phillipnicol/OncoBN.