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Empirical Bayes estimation of a sparse vector of gene expression changes
Stephen W. Erickson, Department of Statistics, UCLA
Chiara Sabatti, Department of Statistics, UCLA
ABSTRACT: Gene microarray technology is often used to compare the expression of thousand of genes
in two different cell lines. Typically, one does not expect measurable changes in transcription
amounts for a large number of genes; furthermore, the noise level of array experiments is rather
high in relation to the available number of replicates. For the purpose of statistical analysis,
inference on the “population” difference in expression for genes across the two cell lines is
often cast in the framework of hypothesis testing, with the null hypothesis being no change in
expression. Given that thousands of genes are investigated at the same time, this requires some
multiple comparison correction procedure to be in place. We argue that hypothesis testing,
with its emphasis on type I error and family analogues, may not address the exploratory nature
of most microarray experiments. We instead propose viewing the problem as one of estimation
of a vector known to have a large number of zero components. In a Bayesian framework, we
describe the prior knowledge on expression changes using mixture priors that incorporate a
mass at zero and we choose a loss function that favors the selection of sparse solutions. We
consider two different models applicable to the microarray problem, depending on the nature
of replicates available, and show how to explore the posterior distributions of the parameters
using MCMC. Simulations show an interesting connection between this Bayesian estimation
framework and both false discovery rate (FDR) control, and misclassification minimizing pro-
cedures. Finally, two empirical examples illustrate the practical advantages of this Bayesian
estimation paradigm
SUGGESTED CITATION: Stephen W. Erickson and Chiara Sabatti,
"Empirical Bayes estimation of a sparse vector of gene expression changes"
(February 1, 2005).
Department of Statistics, UCLA.
Department of Statistics Papers.
Paper 2005020102.
http://repositories.cdlib.org/uclastat/papers/2005020102
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