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A Bayesian mixture model for differential gene expression

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Abstract:

Summary. 

We propose model-based inference for differential gene expression, using a nonparametric Bayesian probability model for the distribution of gene intensities under various conditions. The probability model is a mixture of normal distributions. The resulting inference is similar to a popular empirical Bayes approach that is used for the same inference problem. The use of fully model-based inference mitigates some of the necessary limitations of the empirical Bayes method. We argue that inference is no more difficult than posterior simulation in traditional nonparametric mixture-of-normal models. The approach proposed is motivated by a microarray experiment that was carried out to identify genes that are differentially expressed between normal tissue and colon cancer tissue samples. Additionally, we carried out a small simulation study to verify the methods proposed. In the motivating case-studies we show how the nonparametric Bayes approach facilitates the evaluation of posterior expected false discovery rates. We also show how inference can proceed even in the absence of a null sample of known non-differentially expressed scores. This highlights the difference from alternative empirical Bayes approaches that are based on plug-in estimates.

Keywords: Density estimation; Dirichlet process; Gene expression; Microarrays; Mixture models; Nonparametric Bayes method

Document Type: Research Article

DOI: http://dx.doi.org/10.1111/j.1467-9876.2005.05593.x

Affiliations: University of Texas M. D. Anderson Cancer Center, Houston, USA

Publication date: June 1, 2005

bpl/rssc/2005/00000054/00000003/art00007
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