Reinforcement Learning Data-Acquiring for Causal Inference of Regulatory Networks.

Abstract

Gene regulatory networks (GRNs) consist of multiple interacting genes whose activities govern various cellular processes. The limitations in genomics data and the complexity of the interactions between components often pose huge uncertainties in the models of these biological systems. Meanwhile, inferring/estimating the interactions between components of the GRNs using data acquired from the normal condition of these biological systems is a challenging or, in some cases, an impossible task. Perturbation is a well-known genomics approach that aims to excite targeted components to gather useful data from these systems. This paper models GRNs using the Boolean network with perturbation, where the network uncertainty appears in terms of unknown interactions between genes. Unlike the existing heuristics and greedy data-acquiring methods, this paper provides an optimal Bayesian formulation of the data-acquiring process in the reinforcement learning context, where the actions are perturbations, and the reward measures step-wise improvement in the inference accuracy. We develop a semi-gradient reinforcement learning method with function approximation for learning near-optimal data-acquiring policy. The obtained policy yields near-exact Bayesian optimality with respect to the entire uncertainty in the regulatory network model, and allows learning the policy offline through planning. We demonstrate the performance of the proposed framework using the well-known p53-Mdm2 negative feedback loop gene regulatory network.