Holimap: an accurate and efficient method for solving stochastic gene network dynamics.

Abstract

Gene-gene interactions are crucial to the control of sub-cellular processes but our understanding of their stochastic dynamics is hindered by the lack of simulation methods that can accurately and efficiently predict how the distributions of gene product numbers vary across parameter space. To overcome these difficulties, here we present Holimap (high-order linear-mapping approximation), an approach that approximates the protein or mRNA number distributions of a complex gene regulatory network by the distributions of a much simpler reaction system. We demonstrate Holimap's computational advantages over conventional methods by applying it to predict the stochastic time-dependent dynamics of various gene networks, including transcriptional networks ranging from simple autoregulatory loops to complex randomly connected networks, post-transcriptional networks, and post-translational networks. Holimap is ideally suited to study how the intricate network of gene-gene interactions results in precise coordination and control of gene expression.