Boolean network identification from multiplex time series data

Abstract

Boolean networks (and more general logic models) are useful frameworks to study signal transduction across multiple pathways. Logical models can be learned from a prior knowledge network structure and multiplex phosphoproteomics data. However, most efficient and scalable training methods focus on the comparison of two time-points and assume that the system has reached an early steady state. In this paper, we generalize such a learning procedure to take into account the time series traces of phosphoproteomics data in order to discriminate Boolean networks according to their transient dynamics. To that goal, we exhibit a necessary condition that must be satisfied by a Boolean network dynamics to be consistent with a discretized time series trace. Based on this condition, we use a declarative programming approach (Answer Set Programming) to compute an over-approximation of the set of Boolean networks which fit best with experimental data. Combined with model-checking approaches, we end up with a global learning algorithm and compare it to learning approaches based on static data.