Modeling and analysis of qualitative behavior of gene regulatory networks

ABSTRACT. We describe a hybrid system based framework for modeling gene regulation and other biomolecular networks and a method for analysis of the dynamic behavior of such models. A particular feature of the proposed framework is the focus on qualitative experimentally testable properties of the system. With this goal in mind we introduce the notion of the frame of a hybrid system, which allows for the discretisation of the state space of the network. We propose two different methods for the analysis of this state space. The result of the analysis is a set of attractors (generalizations of attractors used in Boolean models) that characterise the underlying biological system.

Whilst in the general case the problem of finding attractors in the state space is algorithmically undecidable, we demonstrate that our methods work for comparatively complex gene regulatory network model of lambda-phage. For this model we are able to identify attractors corresponding to two known biological behaviors of lambda-phage: lysis and lysogeny and also to show that there are no other stable behavior regions in state space of lambda-phage model.