Encoding Boolean networks into reaction systems for investigating causal dependencies in gene regulation

Abstract

Gene regulatory networks represent the interactions among genes regulating the activation of specific cell functionalities. They have been successfully modelled using Boolean networks, where a set of Boolean variables model the activation state of each gene, and Boolean functions model positive and negative influences among genes. Moreover, when the effect of such influences is additive, threshold Boolean networks, in which Boolean functions are replaced by simpler threshold functions, turned out to be particularly effective.In this paper we propose a systematic translation of threshold Boolean networks into Ehrenfeucht and Rozenberg's reaction systems. Our translation produces a non redundant set of reactions, each using a minimal set of objects. This translation allows us to simulate the behaviour of a general threshold Boolean network by simply executing the (closed) reaction system we obtain, and to investigate causality relations among genes by applying tools available for reaction systems.We implemented our translation in an open-source tool and applied it in two case studies: the gene regulation network of segment polarity in Drosophila melanogaster and the one controlling the differentiation of Th cells in the immune system. In both case studies, we investigate causalities among genes in the reaction system obtained from the translation by applying a tool for the computation of formula based predictors. In the context of the second case study, we show that also Boolean networks with non-additive influences and modelling genes with multiple expression levels can be dealt with by our approach.