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Open Access Research

Modeling stochasticity and variability in gene regulatory networks

David Murrugarra12*, Alan Veliz-Cuba3, Boris Aguilar4, Seda Arat12 and Reinhard Laubenbacher12

Author Affiliations

1 Department of Mathematics, Virginia Tech, Blacksburg, VA 24061-0123, USA

2 Virginia Bioinformatics Institute, Virginia Tech, Blacksburg, VA 24061-0477, USA

3 Department of Mathematics, University of Nebraska-Lincoln, Lincoln, NE 68588, USA

4 Department of Computer Science, Virginia Tech, Blacksburg, VA 24061-0123, USA

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EURASIP Journal on Bioinformatics and Systems Biology 2012, 2012:5  doi:10.1186/1687-4153-2012-5

Published: 6 June 2012

Abstract

Modeling stochasticity in gene regulatory networks is an important and complex problem in molecular systems biology. To elucidate intrinsic noise, several modeling strategies such as the Gillespie algorithm have been used successfully. This article contributes an approach as an alternative to these classical settings. Within the discrete paradigm, where genes, proteins, and other molecular components of gene regulatory networks are modeled as discrete variables and are assigned as logical rules describing their regulation through interactions with other components. Stochasticity is modeled at the biological function level under the assumption that even if the expression levels of the input nodes of an update rule guarantee activation or degradation there is a probability that the process will not occur due to stochastic effects. This approach allows a finer analysis of discrete models and provides a natural setup for cell population simulations to study cell-to-cell variability. We applied our methods to two of the most studied regulatory networks, the outcome of lambda phage infection of bacteria and the p53-mdm2 complex.