Significance analysis of microarrays applied to the ionizing radiation response
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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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Permutation-based methods for calculating q-values and global FDRs are usually applied to control FDR and solve multiple hypothesis testing problems in real biological datasets.
“As a means to control the FDR and solve potential multiple hypothesis testing problems in real biological datasets, we usually apply permutation-based methods for calculating q-values and global FDRs.”
From Accurate proteome-wide label-free quantification by delayed normalization and maximal peptide ratio extraction, termed MaxLFQ (2014) · cites this paper as [55]
SAM analysis detected 366 up-regulated and 474 down-regulated genes in obese WAT compared to lean controls, at a 5% false discovery rate.
“The analysis of the differential gene expression with the Significance analysis of microarrays (SAM) procedure [21], performed on the cDNA measurements with signals recovered in at least 80% of the microarray experiments, detected 366 up- and 474 down-regulated genes, corresponding to a 5% false discovery rate (FDR).”
From Adipose tissue transcriptomic signature highlights the pathological relevance of extracellular matrix in human obesity (2008) · cites this paper as [21]
SAM analysis of cDNA microarray measurements with signals recovered in at least 80% of experiments detected 1,744 up-regulated and 1,627 down-regulated genes at a 5% FDR in subcutaneous WAT before versus three months after gastric bypass.
“The analysis of differential gene expression with the SAM procedure [21], performed on the cDNA measurements with signals recovered in at least 80% of the microarray experiments, detected 1,744 up- and 1,627 down-regulated genes, corresponding to a 5% FDR.”
From Adipose tissue transcriptomic signature highlights the pathological relevance of extracellular matrix in human obesity (2008) · cites this paper as [21]
Significant differential expression was established by imposing a 5% FDR threshold in the SAM selection procedure for all conditions.
“Significant differential expression was established by imposing a 5% FDR threshold in the SAM selection procedure for all conditions.”
From Adipose tissue transcriptomic signature highlights the pathological relevance of extracellular matrix in human obesity (2008) · cites this paper as [21]
Significance analysis of microarrays (SAM) was used to identify miRNAs differentially expressed between samples with a false discovery rate of 0.
“Significance analysis of microarrays (SAM) was used to identify miRNAs differentially expressed between samples (FDR = 0) (Tusher et al. 2001).”
From MicroRNA expression in the adult mouse central nervous system (2008) · cites this paper as Tusher et al. 2001
63 miRNAs showed evidence of being differentially expressed within the CNS (SAM; FDR = 0).
“However, 63 miRNAs showed evidence of being differentially expressed within the CNS (significance analysis of microarrays [SAM]; false discovery rate [ FDR = 0]) (Tusher et al. 2001)”
From MicroRNA expression in the adult mouse central nervous system (2008) · cites this paper as Tusher et al. 2001
miR-142-3p, miR-34a, and miR-223 were enriched in microglial cell lines in this study, and were also up-regulated in multiple sclerosis glial cells and scrapie infection.
“Additionally, a number of miRNAs found to be up-regulated in a recent study profiling glial cells in multiple sclerosis brain lesions, as well as our previous study to determine deregulated miRNAs in scrapie infection, were also identified to be enriched in microglial cell lines in this study [18], [38]. These were miR-142-3p, miR-34a, and miR-223.”
From MicroRNA 146a (miR-146a) Is Over-Expressed during Prion Disease and Modulates the Innate Immune Response and the Microglial Activation State (2012) · cites this paper as [18]
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- Authors
- Tusher, V. G., Tibshirani, R., & Chu, G.
- Affiliations
- Stanford Medicine (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2001-04-17
- Volume
- 98
- Issue
- 9
- Pages
- 5116-5121
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC33173
- 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
- green
- www.ncbi.nlm.nih.gov
- 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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