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Bioinformatics Advance Access published online on July 28, 2008
Bioinformatics, doi:10.1093/bioinformatics/btn367
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© The Author (2008). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Modelling non-stationary gene regulatory processes with a non-homogeneous Bayesian network and the allocation sampler

Marco Grzegorczyk a, Dirk Husmeier b, Kieron D. Edwards e, Peter Ghazal a,c and Andrew J. Millar a,d

a Centre for Systems Biology at Edinburgh (CSBE), United Kingdom
b Biomathematics and Statistics Scotland (BioSS), Edinburgh, United Kingdom
c Division of Pathway Medicine (DPM), University of Edinburgh, United Kingdom
d Institute of Molecular Plant Sciences, University of Edinburgh, United Kingdom
e Advanced Technologies Cambridge, United Kingdom

*To whom correspondence should be addressed. Dr. Dirk Husmeier, E-mail: dirk{at}bioss.ac.uk


  Abstract

Motivation: The objective of the present paper is to propose and evaluate a probabilistic approach based on Bayesian networks for modelling non-homogeneous and non-linear gene-regulatory processes. The method is based on a mixture model, using latent variables to assign individual measurements to different classes. The practical inference follows the Bayesian paradigm and samples the network structure, the number of classes and the assignment of latent variables from the posterior distribution with MCMC, using the recently proposed allocation sampler as an alternative to RJMCMC.

Results: We have evaluated the method using three criteria: network reconstruction, statistical significance and biological plausibility. In terms of network reconstruction, we found improved results both for a synthetic network of known structure and for a small real regulatory network derived from the literature. We have assessed the statistical significance of the improvement on gene expression time series for two different systems (viral challenge of macrophages, and circadian rhythms in plants), where the proposed new scheme tends to outperform the classical BGe score. Regarding biological plausibility, we found that the inference results obtained with the proposed method were in excellent agreement with biological findings, predicting dichotomies that one would expect to find in the studied systems.

Availability: Two supplementary papers on theoretical (T) and experimental (E) aspects and the data sets used in our study are available from http://www.bioss.ac.uk/associates/marco/supplement/

Contact: marco{at}bioss.ac.uk, dirk{at}bioss.ac.uk

Associate Editor: Dr. Trey Ideker

Received on May 17, 2008; revised on July 9, 2008; accepted on July 14, 2008

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