Structure and timescale analysis in genetic regulatory networks

Abstract

Regulation of gene expression is achieved through networks of interactions among genes and gene products. Genetic networks are sometimes described in a qualitative way, for instance by means of discrete or even Boolean models. Even when such models accurately reflect the basic structure of interactions, they are in general not suitable for robustness analysis, as one needs to study the effect of biologically-relevant perturbations on the dynamics of the system. This paper is concerned with the study of the robustness and fragility of gene regulation networks to variability in the timescales of the distinct biological processes involved. It explores and compares two methods: introducing asynchronous updates in a Boolean model, or integrating the Boolean rules in a continuous, piecewise linear model. As an example, the segment polarity network of the fruit fly is analyzed. A theoretical characterization is given of the model's ability to predict the correct development of the segmented embryo, in terms of the specific timescales of the various regulation interactions