Empirical Bayes Estimation of Gene-Specific Effects in Micro-array Research

Abstract

Micro-array technology allows investigators the opportunity to measure expression levels of thousands of genes simultaneously. However, investigators are also faced with the challenge of simultaneous estimation of gene expression differences for thousands of genes with very small sample sizes. Traditional estimators of differences between treatment means (ordinary least squares estimators or OLS) are not the best estimators if interest is in estimation of gene expression differences for an ensemble of genes. In the case that gene expression differences are regarded as exchangeable samples from a common population, estimators are available that result in much smaller average mean-square error across the population of gene expression difference estimates. We have simulated the application of such an estimator, namely an empirical Bayes (EB) estimator of random effects in a hierarchical linear model (normal-normal). Simulation results revealed mean-square error as low as 0.05 times the mean-square error of OLS estimators (i.e., the difference between treatment means). We applied the analysis to an example dataset as a demonstration of the shrinkage of EB estimators and of the reduction in mean-square error, i.e., increase in precision, associated with EB estimators in this analysis. The method described here is available in software that is available at http://www.soph.uab.edu/ssg.asp?id=1087.

Department(s)

Mathematics and Statistics

Sponsor(s)

Frederick Gardner Cottrell Foundation
National Institutes of Health (U.S.)
National Science Foundation (U.S.)
University of Alabama Health Services Foundation

Keywords and Phrases

Empirical bayes; Estimation; Micro-array; Shrinkage

Document Type

Article - Journal

Document Version

Citation

File Type

text

Language(s)

English

Rights

© 2005 Springer Berlin / Heidelberg, All rights reserved.

Publication Date

01 Jan 2005

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