Bioinformatics Advance Access originally published online on September 7, 2004
Bioinformatics 2005 21(3):349-356; doi:10.1093/bioinformatics/bti014
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Bioinformatics vol. 21 issue 3 © Oxford University Press 2005; all rights reserved.
A Bayesian approach to reconstructing genetic regulatory networks with hidden factors
1Department of Computer Science & Engineering, State University of New York at Buffalo 201 Bell Hall, Buffalo, NY 14260-2000, USA
2School of Biosciences, University of Birmingham Edgbaston, Birmingham B15 2TT, UK
3Gatsby Computational Neuroscience Unit, University College London 17 Queen Square, London WC1N 3AR, UK
4Keck Graduate Institute of Applied Life Sciences 535 Watson Drive, Claremont, CA 91171, USA
*To whom correspondence should be addressed.
Motivation: We have used state-space models (SSMs) to reverse engineer transcriptional networks from highly replicated gene expression profiling time series data obtained from a well-established model of T cell activation. SSMs are a class of dynamic Bayesian networks in which the observed measurements depend on some hidden state variables that evolve according to Markovian dynamics. These hidden variables can capture effects that cannot be directly measured in a gene expression profiling experiment, for example: genes that have not been included in the microarray, levels of regulatory proteins, the effects of mRNA and protein degradation, etc.
Results: We have approached the problem of inferring the model structure of these state-space models using both classical and Bayesian methods. In our previous work, a bootstrap procedure was used to derive classical confidence intervals for parameters representing ‘gene–gene’ interactions over time. In this article, variational approximations are used to perform the analogous model selection task in the Bayesian context. Certain interactions are present in both the classical and the Bayesian analyses of these regulatory networks. The resulting models place JunB and JunD at the centre of the mechanisms that control apoptosis and proliferation. These mechanisms are key for clonal expansion and for controlling the long term behavior (e.g. programmed cell death) of these cells.
Availability: Supplementary data is available at http://public.kgi.edu/wild/index.htm and Matlab source code for variational Bayesian learning of SSMs is available at http://www.cse.buffalo.edu/faculty/mbeal/software.html
Contact: David_Wild{at}kgi.edu
Received on December 1, 2003; revised on August 30, 2004; accepted on August 31, 2004
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