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Bioinformatics Advance Access published online on October 9, 2008
Bioinformatics, doi:10.1093/bioinformatics/btn527
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© The Author (2008). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Stochastic dynamics of genetic networks: modelling and parameter identification

Eugenio Cinquemani *, Andreas Milias-Argeitis , Sean Summers and John Lygeros

Automatic Control Laboratory, ETH, 8092 Zurich, Switzerland

*To whom correspondence should be addressed. Dr. Eugenio Cinquemani, E-mail: cinquemani{at}control.ee.ethz.ch


  Abstract

Motivation: Identification of regulatory networks is typically based on deterministic models of gene expression. Increasing experimental evidence suggests that the gene regulation process is intrinsically random. To ensure accurate and thorough processing of the experimental data, stochasticity must be explicitly accounted for both at the modelling stage and in the design of the identification algorithms.

Results: We propose a model of gene expression in prokaryotes where transcription is described as a probabilistic event, whereas protein synthesis and degradation are captured by first order deterministic kinetics. Based on this model and assuming that the network of interactions is known, a method for estimating unknown parameters such as synthesis and binding rates from the outcomes of multiple time course experiments is introduced. The method accounts naturally for sparse, irregularly sampled and noisy data and is applicable to gene networks of arbitrary size. The performance of the method is evaluated on a model of nutrient stress response in Escherichia coli.

Contact: cinquemani{at}control.ee.ethz.ch

Associate Editor: Prof. Alfonso Valencia

Received on January 13, 2008; revised on September 17, 2008; accepted on October 7, 2008

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[Abstract] [Full Text] [PDF]


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