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Modeling Gene Regulatory Networks with Delayed Stochastic Dynamics
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Author(s): Andre S. Ribeiro (Tampere University of Technology, Finland), John J. Grefenstette (George Mason University, USA)and Stuart A. Kauffman (University of Calgary, Canada)
Copyright: 2010
Pages: 21
Source title:
Handbook of Research on Computational Methodologies in Gene Regulatory Networks
Source Author(s)/Editor(s): Sanjoy Das (Kansas State University, USA), Doina Caragea (Kansas State University, USA), Stephen Welch (Kansas State University, USA)and William H. Hsu (Kansas State University, USA)
DOI: 10.4018/978-1-60566-685-3.ch008
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Abstract
We present a recently developed modeling strategy of gene regulatory networks (GRN) that uses the delayed stochastic simulation algorithm to drive its dynamics. First, we present experimental evidence that led us to use this strategy. Next, we describe the stochastic simulation algorithm (SSA), and the delayed SSA, able to simulate time-delayed events. We then present a model of single gene expression. From this, we present the general modeling strategy of GRN. Specific applications of the approach are presented, beginning with the model of single gene expression which mimics a recent experimental measurement of gene expression at single-protein level, to validate our modeling strategy. We also model a toggle switch with realistic noise and delays, used in cells as differentiation pathway switches. We show that its dynamics differs from previous modeling strategies predictions. As a final example, we model the P53-Mdm2 feedback loop, whose malfunction is associated to 50% of cancers, and can induce cells apoptosis. In the end, we briefly discuss some issues in modeling the evolution of GRNs, and outline some directions for further research.
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