Bioinformatics Vol. 19 no. 18 2003
pages 2448-2455
© 2003 Oxford University Press
A random variance model for detection of differential gene expression in small microarray experiments
National Cancer Institute Biometric Research Branch, 6130 Executive Blvd., MSC 7434, Bethesda, MD 20892-7434, USA
Received on March 28, 2003
; revised on June 5, 2003
; accepted on June 25, 2003
Motivation: Microarray techniques provide a valuable way of characterizing the molecular nature of disease. Unfortunately expense and limited specimen availability often lead to studies with small sample sizes. This makes accurate estimation of variability difficult, since variance estimates made on a gene by gene basis will have few degrees of freedom, and the assumption that all genes share equal variance is unlikely to be true.
Results: We propose a model by which the within gene variances are drawn from an inverse gamma distribution, whose parameters are estimated across all genes. This results in a test statistic that is a minor variation of those used in standard linear models. We demonstrate that the model assumptions are valid on experimental data, and that the model has more power than standard tests to pick up large changes in expression, while not increasing the rate of false positives.
Availability: This method is incorporated into BRB-ArrayTools version 3.0 (http://linus.nci.nih.gov/BRB-ArrayTools.html).
Supplementary material: ftp://linus.nci.nih.gov/pub/techreport/RVM_supplement.pdf
Contact: wrightge{at}mail.nih.gov
* To whom correspondence should be addressed.
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