Methods controlling 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 non-differentially expressed genes in control data sets.
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