Qualitative simulation of genetic regulatory networks using piecewise-linear models
H. de Jong, J.-L. Gouzé, C. Hernandez, M. Page, T. Sari, J. Geiselmann
Bulletin of Mathematical Biology, 66(2):301-340, 2004.
In order to cope with the large amounts of data that have become available in genomics, mathematical tools for the analysis of networks of interactions between genes, proteins, and other molecules are indispensable. We present a method for the qualitative simulation of genetic regulatory networks, based on a class of piecewise-linear (PL) differential equations that has been well-studied in mathematical biology. The simulation method is well-adapted to state-of-the-art measurement techniques in genomics, which often provide qualitative and coarse-grained descriptions of genetic regulatory networks. Given a qualitative model of a genetic regulatory network, consisting of a system of PL differential equations and inequality constraints on the parameter values, the method produces a graph of qualitative states and transitions between qualitative states, summarizing the qualitative dynamics of the system. The qualitative simulation method has been implemented in Java in the computer tool Genetic Network Analyzer.