Significance analysis of microarrays applied to the ionizing radiation response

Proceedings of the National Academy of Sciences of the United States of America - Tập 98 Số 9 - Trang 5116-5121 - 2001
Virginia Goss Tusher1, Robert Tibshirani1, Gilbert Chu1
1Departments 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

Tóm tắt

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.

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Tài liệu tham khảo

10.1073/pnas.95.25.14863

10.1126/science.287.5454.873

10.1126/science.285.5425.251

10.1126/science.287.5462.2486

10.1089/jir.1996.16.395

10.1016/0092-8674(93)90499-G

10.1002/j.1460-2075.1994.tb06807.x

10.1016/S0092-8674(00)81774-2

10.1126/science.277.5331.1495

10.1016/S0021-9258(19)49610-5

10.1128/MCB.15.12.7143

10.1083/jcb.142.3.787

10.1016/S0092-8674(00)80419-5

10.1002/(SICI)1521-4141(199912)29:12<3956::AID-IMMU3956>3.0.CO;2-G

10.1016/S0304-3835(96)04459-X

10.1084/jem.180.2.757

10.4049/jimmunol.164.5.2533

10.1074/jbc.275.1.147

10.1016/0092-8674(95)90289-9

10.1128/MCB.20.10.3705-3714.2000

10.1016/S1097-2765(00)80132-X

10.1016/S1097-2765(00)80252-X

10.1016/0092-8674(92)90593-2

10.1073/pnas.96.2.424

10.1128/MCB.19.1.12

10.2307/3576562

10.2307/3579583

10.1002/9780470316672

P Westfall, S Young Resampling-Based Multiple Testing (Wiley, New York, 1993).

J Hsu Multiple Comparisons: Theory and Methods (Chapman & Hall, London, 1996).

Y Benjamini, Y Hochberg J R Stat Soc B 57, 289–300 (1995).

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Proceedings of the National Academy of Sciences of the United States of America

Tập 98 Số 9

5116-5121

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