Significance analysis of microarrays applied to the ionizing radiation response

Microarrays can measure the expression of thousands of genes to identify ch anges in expression between different biological states. Methods are needed to determine the significance of these changes while accounting for the en ormous number of genes. We describe a method, Significance Analysis of Micr oarrays (SAM). that assigns a score to each gene on the basis of change in gene expression relative to the standard deviation of repeated measurements . For genes with scores greater than an adjustable threshold. SAM uses perm utations of the repeated measurements to estimate the percentage of genes i dentified by chance, the false discovery rate (FDR). When the transcription al response of human cells to ionizing radiation was measured by microarray s. SAM identified 34 genes that changed at least 1.5-fold with an estimated FDR of 12%. compared with FDRs of 60 and 84% by using conventional methods of analysis. Of the 34 genes, 19 were involved in cell cycle regulation an d 3 in apoptosis, Surprisingly, four nucleotide excision repair genes were induced, suggesting that this repair pathway for UV-damaged DNA might play a previously unrecognized role in repairing DNA damaged by ionizing radiati on.