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Bioinformatics Advance Access originally published online on July 28, 2008
Bioinformatics 2008 24(18):2071-2078; 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 1,2,*, Dirk Husmeier 2,3,*, Kieron D. Edwards 4, Peter Ghazal 2,5 and Andrew J. Millar 1,2

1School of Biological Sciences, The University of Edinburgh, Swann Building, King's Buildings, Edinburgh EH9 3JR, 2Centre for Systems Biology at Edinburgh (CSBE), Darwin Building, King's Buildings, Edinburgh EH9 3JU, 3Biomathematics and Statistics Scotland (BioSS), JCMB, King's Buildings, Edinburgh EH9 3JZ, 4Advanced Technologies (Cambridge) Ltd, Cambridge CB4 0WA and 5Division of Pathway Medicine (DPM), Medical School, The University of Edinburgh, Chancellor's Buildings, Edinburgh EH16 4SB, UK

*To whom correspondence should be addressed.


  Abstract

Method: The objective of the present article 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 Markov Chain Monte Carlo (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 experi-mental (E) aspects and the datasets 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: Trey Ideker

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

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