Automated abstraction methodology for genetic regulatory networks

Abstract

In order to efficiently analyze the complicated regulatory systems often encountered in biological settings, abstraction is essential. This paper presents an automated abstraction methodology that systematically reduces the small-scale complexity found in genetic regulatory network models, while broadly preserving the large-scale system behavior. Our method first reduces the number of reactions by using rapid equilibrium and quasi-steady-state approximations as well as a number of other stoichiometry-simplifying techniques, which together result in substantially shortened simulation time. To further reduce analysis time, our method can represent the molecular state of the system by a set of scaled Boolean (or n-ary) discrete levels. This results in a chemical master equation that is approximated by a Markov chain with a much smaller state space providing significant analysis time acceleration and computability gains. The genetic regulatory network for the phage λ lysis/lysogeny decision switch is used as an example throughout the paper to help illustrate the practical applications of our methodology. © Springer-Verlag Berlin Heidelberg 2006.