Statistical Science

Laplace Approximated EM Microarray Analysis: An Empirical Bayes Approach for Comparative Microarray Experiments

Haim Bar, James Booth, Elizabeth Schifano, and Martin T. Wells

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A two-groups mixed-effects model for the comparison of (normalized) microarray data from two treatment groups is considered. Most competing parametric methods that have appeared in the literature are obtained as special cases or by minor modification of the proposed model. Approximate maximum likelihood fitting is accomplished via a fast and scalable algorithm, which we call LEMMA (Laplace approximated EM Microarray Analysis). The posterior odds of treatment × gene interactions, derived from the model, involve shrinkage estimates of both the interactions and of the gene specific error variances. Genes are classified as being associated with treatment based on the posterior odds and the local false discovery rate (f.d.r.) with a fixed cutoff. Our model-based approach also allows one to declare the non-null status of a gene by controlling the false discovery rate (FDR). It is shown in a detailed simulation study that the approach outperforms well-known competitors. We also apply the proposed methodology to two previously analyzed microarray examples. Extensions of the proposed method to paired treatments and multiple treatments are also discussed.

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Statist. Sci., Volume 25, Number 3 (2010), 388-407.

First available in Project Euclid: 4 January 2011

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EM algorithm empirical Bayes Laplace approximation LEMMA LIMMA linear mixed models local false discovery rate microarray analysis mixture model two-groups model


Bar, Haim; Booth, James; Schifano, Elizabeth; Wells, Martin T. Laplace Approximated EM Microarray Analysis: An Empirical Bayes Approach for Comparative Microarray Experiments. Statist. Sci. 25 (2010), no. 3, 388--407. doi:10.1214/10-STS339.

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