Bioinformatics Advance Access originally published online on December 5, 2007
Bioinformatics 2008 24(6):833-839; doi:10.1093/bioinformatics/btm607
Bayesian ranking of biochemical system models
Department of Computing Science, University of Glasgow, Glasgow, G12 8QQ, UK
*To whom correspondence should be addressed.
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Abstract |
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Motivation: There often are many alternative models of a biochemical system. Distinguishing models and finding the most suitable ones is an important challenge in Systems Biology, as such model ranking, by experimental evidence, will help to judge the support of the working hypotheses forming each model.
Bayes factors are employed as a measure of evidential preference for one model over another. Marginal likelihood is a key component of Bayes factors, however computing the marginal likelihood is a difficult problem, as it involves integration of nonlinear functions in multidimensional space. There are a number of methods available to compute the marginal likelihood approximately. A detailed investigation of such methods is required to find ones that perform appropriately for biochemical modelling.
Results: We assess four methods for estimation of the marginal likelihoods required for computing Bayes factors. The Prior Arithmetic Mean estimator, the Posterior Harmonic Mean estimator, the Annealed Importance Sampling and the Annealing-Melting Integration methods are investigated and compared on a typical case study in Systems Biology. This allows us to understand the stability of the analysis results and make reliable judgements in uncertain context. We investigate the variance of Bayes factor estimates, and highlight the stability of the Annealed Importance Sampling and the Annealing-Melting Integration methods for the purposes of comparing nonlinear models.
Availability: Models used in this study are available in SBML format as the supplementary material to this article.
Contact: vvv{at}dcs.gla.ac.uk
Supplementary information: Supplementary data are available at Bioinformatics online.
Associate Editor: Limsoon Wong
Received on August 28, 2007; revised on October 26, 2007; accepted on December 3, 2007
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