Significance analysis of microarrays applied to the ionizing radiation response
- *Departments of Medicine and Biochemistry, Stanford University, 269 Campus Drive, Center for Clinical Sciences Research 1115, Stanford, CA 94305-5151; and †Department of Health Research and Policy and Department of Statistics, Stanford University, Stanford, CA 94305
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Communicated by Bradley Efron, Stanford University, Stanford, CA (received for review December 1, 2000)
Abstract
Microarrays can measure the expression of thousands of genes to identify changes in expression between different biological states. Methods are needed to determine the significance of these changes while accounting for the enormous number of genes. We describe a method, Significance Analysis of Microarrays (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 permutations of the repeated measurements to estimate the percentage of genes identified by chance, the false discovery rate (FDR). When the transcriptional response of human cells to ionizing radiation was measured by microarrays, 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 and 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 radiation.
Footnotes
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↵ ‡ To whom reprint requests should be addressed. E-mail: chu{at}cmgm.stanford.edu.
- Abbreviations:
- SAM,
- significance analysis of microarrays;
- FDR,
- false discovery rate;
- IR,
- ionizing radiation;
- FWER,
- family-wise error rate
- Copyright © 2001, The National Academy of Sciences
