The modeling challenge Regulation is a key aspect of biological systems, all the way from the molecular scale to the ecological one. Gaining a precise understanding of regulation is one of the main goals of systems biology. This discipline has emerged from the synergy between cell biology and cybernetics [WIE 48], from the collaboration of biologists, physicists and computer scientists [IDE 01]. The modeling approach presented in this chapter derives from this heritage by studying the interactions of components of a biological system and analyzing how these interactions impact the function and behavior of the system as a whole. Here, we will focus on applications to genetics, but the potential field of the approach is broader: the Process Hitting framework is relevant to any interactive system, whether it is a biological regulatory network, a logistic scheme or an embedded system. The recent progress in molecular biology has made it possible to obtain a comprehensive map of the genomes of many living organisms. Simultaneously, the development of DNA micro array technology has given access to time series data of the expression of several thousands of genes. One of the main challenges now is to Chapter written by Loïc PAULEVÉ and Courtney CHANCELLOR and Maxime FOLSCHETTE and Morgan MAGNIN and Olivier ROUX.
Modeling frameworks bring structure and analysis tools to large and non-intuitive systems but come with certain inherent assumptions and limitations, sometimes to an inhibitive extent. By building bridges in existing models, we can exploit the advantages of each, widening the range of analysis possible for larger, more detailed models of gene regulatory networks. In this paper, we create just such a link between Process Hitting [6,7,8], a recently introduced discrete framework, and the Chemical Master Equation in such a way that allows the application of powerful numerical techniques, namely Proper Generalized Decomposition [1,2,3], to overcome the curse of dimensionality. With these tools in hand, one can exploit the formal analysis of discrete models without sacrificing the ability to obtain a full space state solution, widening the scope of analysis and interpretation possible. As a demonstration of the utility of this methodology, we have applied it here to the p53-mdm2 network [4,5], a widely studied biological regulatory network.
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