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

BMC Genomics. 2007 Apr 9;8:96. doi: 10.1186/1471-2164-8-96.

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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Data Interpretation, Statistical*
  • False Positive Reactions
  • Gene Expression Regulation
  • Mice
  • Mice, Transgenic
  • Molecular Diagnostic Techniques
  • Oligonucleotide Array Sequence Analysis*
  • ROC Curve
  • Reverse Transcriptase Polymerase Chain Reaction