Influence Networks compared with Reaction Networks: Semantics, Expressivity and Attractors


Biochemical reaction networks are one of the most widely used formalism in systems biology to describe the molecular mechanisms of high-level cell processes. However modellers also reason with influence diagrams to represent the positive and negative influences between molecular species and may find an influence network useful in the process of building a reaction network. In this paper, we introduce a formalism of influence networks with forces, and equip it with a hierarchy of Boolean, Petri net, stochastic and differential semantics, similarly to reaction networks with rates. We show that the expressive power of influence networks is the same as that of reaction networks under the differential semantics, but weaker under the discrete semantics. Furthermore, the hierarchy of semantics leads us to consider a (positive) Boolean semantics without test for absence, that we compare with the (negative) Boolean semantics with test for absence of gene regulatory networks à la Thomas. We study the monotonicity properties of the positive semantics and derive from them an algorithm to compute attractors in both the positive and negative Boolean semantics. We illustrate our results on models of the literature about the p53/Mdm2 DNA damage repair system, the circadian clock, and the influence of MAPK signaling on cell-fate decision in urinary bladder cancer.

IEEE/ACM Transactions on Computational Biology and Bioinformatics, PP (99):1-14