Cited by 10,568Gene expression and cancer classificationBioinformatics and Genomic NetworksBreast Cancer Treatment Studies

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Significance analysis of microarrays applied to the ionizing radiation response

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Tusher, Virginia Goss, Tibshirani, Robert, Chu, Gilbert·2001·Proceedings of the National Academy of Sciences

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.

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Metadata

Authors
Tusher, V. G., Tibshirani, R., & Chu, G.
Affiliations
Stanford Medicine (US)
Venue
Proceedings of the National Academy of Sciences
Published
2001-04-17
Volume
98
Issue
9
Pages
5116-5121
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W4294107304
Cited by
10,568
References
31
Citations by year
2026: 55 · 2025: 96 · 2024: 152 · 2023: 269 · 2022: 204 · 2021: 246 · 2020: 268 · 2019: 272 · 2018: 270 · 2017: 358 · 2016: 402 · 2015: 466 · 2014: 518 · 2013: 599 · 2012: 677
FWCI
95.32
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (1r41ca075675-01)
  • National Cancer Institute (CA75675, CA77302, R01CA077302)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene expression and cancer classification
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
Keywords
significance analysis of microarrays, false discovery rate, ionizing radiation response, transcriptional response, cell cycle regulation, apoptosis, nucleotide excision repair, DNA repair, UV-damaged DNA, human cells
MeSH terms
Cell Cycle, DNA Damage, DNA Repair, Gene Expression Regulation, Humans, Radiation, Ionizing, RNA, Messenger, Statistics as Topic, Tumor Cells, Cultured, Reproducibility of Results, Down-Regulation, Up-Regulation, Apoptosis, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling

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