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Open Access Highly Accessed Methodology article

Fisher's combined p-value for detecting differentially expressed genes using Affymetrix expression arrays

Ann Hess* and Hari Iyer

Author Affiliations

Department of Statistics, Colorado State University, Fort, Collins, CO, 80523, USA

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BMC Genomics 2007, 8:96  doi:10.1186/1471-2164-8-96

Published: 9 April 2007

Abstract

Background

Currently, most tests of differential gene expression using Affymetrix expression array data are performed using expression summary values representing each probe set on a microarray. Recently testing methods have been proposed which incorporate probe level information. We propose a new approach that uses Fisher's method of combining evidence from multiple sources of information. Specifically, we combine p-values from probe level tests of significance.

Results

The combined p method and other competing methods were compared using three spike-in datasets (where probe sets corresponding differentially spiked transcripts are known) and array data from a biological study validated with qRT-PCR. Based on power and false discovery rates computed for the spike-in datasets, we demonstrate that the combined p method compares favorably with other methods. We find that probe level testing methods select many of the same genes as differentially expressed. We illustrate the use of the combined p method for diagnostic purposes using examples.

Conclusion

Combined p is a promising alternative to existing methods of testing for differential gene expression. In addition, the combined p method is particularly well suited as a diagnostic tool for exploratory analysis of microarray data.