Towards the uniform distribution of null P values on Affymetrix microarrays

Methods to control false-positive rates require that P values of genes that are not differentially expressed follow a uniform distribution. Commonly used microarray statistics can generate P values that do not meet this assumption. We show that poorly characterized variance, imperfect normalization, and cross-hybridization are among the many causes of this non-uniform distribution. We demonstrate a simple technique that produces P values that are close to uniform for nondifferentially expressed genes in control datasets.