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

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.

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.

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.