Bioinformatics Vol. 19 no. 15 2003
Pages 1945-1951
© 2003 Oxford University Press
Local-pooled-error test for identifying differentially expressed genes with a small number of replicated microarrays
1 Hospital West Complex, Rm. 3181, P.O. Box 800717, University of Virginia School of Medicine, Charlottesville, VA 22908, USA and 2 Insightful Corporation, 2505 Meridian Parkway Suite 175, Durham, NC 27713, USA
Received on October 31, 2002
; revised on March 4, 2003
; accepted on April 25, 2003
Motivation: In microarray studies gene discovery based on fold-change values is often misleading because error variability for each gene is heterogeneous under different biological conditions and intensity ranges. Several statistical testing methods for differential gene expression have been suggested, but some of these approaches are underpowered and result in high false positive rates because within-gene variance estimates are based on a small number of replicated arrays.
Results: We propose to use local-pooled-error (LPE) estimates and robust statistical tests for evaluating significance of each gene's differential expression. Our LPE estimation is based on pooling errors within genes and between replicate arrays for genes in which expression values are similar. We have applied our LPE method to compare gene expression in naïve and activated CD8+ T-cells. Our results show that the LPE method effectively identifies significant differential-expression patterns with a small number of replicated arrays.
Availability: The methodology is implemented with S-PLUS and R functions available at http://hesweb1.med.virginia.edu/bioinformatics
Contact: nj7w{at}virginia.edu
* To whom correspondence should be addressed.
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