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Hybrid modeling and simulation of genetic regulatory networks : A qualitative approach

H. de Jong, J.-L. Gouzé, C. Hernandez, M. Page, T. Sari, J. Geiselmann

A. Pnueli, O. Maler (eds), Hybrid Systems : Computation and Control, HSCC 2003, Lecture Notes in Computer Science 2623, Springer-Verlag, Berlin, 267-282, 2003.


The study of genetic regulatory networks has received a major impetus from the recent development of experimental techniques allowing the measurement of patterns of gene expression in a massively parallel way. This experimental progress calls for the development of appropriate computer tools for the modeling and simulation of gene regulation processes. We present a method for the hybrid modeling and simulation of genetic regulatory networks, based on a class of piecewise-linear (PL) differential equations that has been well-studied in mathematical biology. Distinguishing characteristics of the method are that it makes qualitative predictions of the behavior of regulatory systems and that it deals with discontinuities in the right-hand side of the differential equations. The simulation method has been implemented in Java in the computer tool Genetic Network Analyzer (GNA). The method and the tool have been used to analyze several networks of biological interest, including the network underlying the initiation of sporulation in Bacillus subtilis.