Vytenis Šliogeris

Sotiris Moschoyiannis, Evangelos Chatzaroulas, Vytenis Sliogeris et al.

The ability to direct a Probabilistic Boolean Network (PBN) to a desired state is important to applications such as targeted therapeutics in cancer biology. Reinforcement Learning (RL) has been proposed as a framework that solves a discrete-time optimal control problem cast as a Markov Decision Process. We focus on an integrative framework powered by a model-free deep RL method that can address different flavours of the control problem (e.g., with or without control inputs; attractor state or a subset of the state space as the target domain). The method is agnostic to the distribution of probabilities for the next state, hence it does not use the probability transition matrix. The time complexity is linear on the time steps, or interactions between the agent (deep RL) and the environment (PBN), during training. Indeed, we explore the scalability of the deep RL approach to (set) stabilization of large-scale PBNs and demonstrate successful control on large networks, including a metastatic melanoma PBN with 200 nodes.

Vytenis Šliogeris, Leandros Maglaras, Sotiris Moschoyiannis

Probabilistic Boolean Networks have been proposed for estimating the behaviour of dynamical systems as they combine rule-based modelling with uncertainty principles. Inferring PBNs directly from gene data is challenging however, especially when data is costly to collect and/or noisy, e.g., in the case of gene expression profile data. In this paper, we present a reproducible method for inferring PBNs directly from real gene expression data measurements taken when the system was at a steady state. The steady-state dynamics of PBNs is of special interest in the analysis of biological machinery. The proposed approach does not rely on reconstructing the state evolution of the network, which is computationally intractable for larger networks. We demonstrate the method on samples of real gene expression profiling data from a well-known study on metastatic melanoma. The pipeline is implemented using Python and we make it publicly available.