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.
Keywords
DNA microarrayGeneSignificance analysis of microarraysBiologyIonizing radiationGene expressionDNA repairGeneticsMicroarrayGene expression profilingBiological pathwayComputational biologyDNAMolecular biology
Affiliated Institutions
Related Publications
Empirical Bayes Analysis of a Microarray Experiment
AbstractMicroarrays are a novel technology that facilitates the simultaneous measurement of thousands of gene expression levels. A typical microarray experiment can produce mill...
Quantitative Monitoring of Gene Expression Patterns with a Complementary DNA Microarray
A high-capacity system was developed to monitor the expression of many genes in parallel. Microarrays prepared by high-speed robotic printing of complementary DNAs on glass were...
Distinctive gene expression patterns in human mammary epithelial cells and breast cancers
cDNA microarrays and a clustering algorithm were used to identify patterns of gene expression in human mammary epithelial cells growing in culture and in primary human breast tu...
Gene expression profiling of alveolar rhabdomyosarcoma with cDNA microarrays.
Several forms of human sarcoma, lymphoma, and leukemia are characterized by somatically acquired chromosome translocations that result in fusion genes that encode chimeric trans...
Analysis of gene expression profiles in normal and neoplastic ovarian tissue samples identifies candidate molecular markers of epithelial ovarian cancer
Epithelial ovarian cancer is the leading cause of death from gynecologic cancer, in part because of the lack of effective early detection methods. Although alterations of severa...
Publication Info
- Year
- 2001
- Type
- article
- Volume
- 98
- Issue
- 9
- Pages
- 5116-5121
- Citations
- 10601
- Access
- Closed
External Links
Social Impact
Altmetric
PlumX Metrics
Social media, news, blog, policy document mentions
Citation Metrics
10601
OpenAlex
Cite This
Virginia Goss Tusher,
Robert Tibshirani,
Gilbert Chu
(2001).
Significance analysis of microarrays applied to the ionizing radiation response.
Proceedings of the National Academy of Sciences
, 98
(9)
, 5116-5121.
https://doi.org/10.1073/pnas.091062498
Identifiers
- DOI
- 10.1073/pnas.091062498