title: Fisher's combined p-value for detecting differentially expressed genes using Affymetrix expression arrays.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Statistics, Colorado State University, Fort Collins, CO 80523, USA. hess@stat.colostate.edu
authors.forename: Ann
authors.initials: A
authors.lastname: Hess
authors.forename: Hari
authors.initials: H
authors.lastname: Iyer
mesh_terms: D000818:Animals; D003627:Data Interpretation, Statistical; D005189:False Positive Reactions; D005786:Gene Expression Regulation; D051379:Mice; D008822:Mice, Transgenic; D025202:Molecular Diagnostic Techniques; D020411:Oligonucleotide Array Sequence Analysis; D012372:ROC Curve; D020133:Reverse Transcriptase Polymerase Chain Reaction