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Gene set analyses for interpreting microarray experiments on prokaryotic organisms
BACKGROUND: Despite the widespread usage of DNA microarrays, questions remain about how best to interpret the wealth of gene-by-gene transcriptional levels that they measure. Recently, methods have been proposed which use biologically defined sets of genes in interpretation, instead of examining res...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2008
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2587482/ https://www.ncbi.nlm.nih.gov/pubmed/18986519 http://dx.doi.org/10.1186/1471-2105-9-469 |
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author | Tintle, Nathan L Best, Aaron A DeJongh, Matthew Van Bruggen, Dirk Heffron, Fred Porwollik, Steffen Taylor, Ronald C |
author_facet | Tintle, Nathan L Best, Aaron A DeJongh, Matthew Van Bruggen, Dirk Heffron, Fred Porwollik, Steffen Taylor, Ronald C |
author_sort | Tintle, Nathan L |
collection | PubMed |
description | BACKGROUND: Despite the widespread usage of DNA microarrays, questions remain about how best to interpret the wealth of gene-by-gene transcriptional levels that they measure. Recently, methods have been proposed which use biologically defined sets of genes in interpretation, instead of examining results gene-by-gene. Despite a serious limitation, a method based on Fisher's exact test remains one of the few plausible options for gene set analysis when an experiment has few replicates, as is typically the case for prokaryotes. RESULTS: We extend five methods of gene set analysis from use on experiments with multiple replicates, for use on experiments with few replicates. We then use simulated and real data to compare these methods with each other and with the Fisher's exact test (FET) method. As a result of the simulation we find that a method named MAXMEAN-NR, maintains the nominal rate of false positive findings (type I error rate) while offering good statistical power and robustness to a variety of gene set distributions for set sizes of at least 10. Other methods (ABSSUM-NR or SUM-NR) are shown to be powerful for set sizes less than 10. Analysis of three sets of experimental data shows similar results. Furthermore, the MAXMEAN-NR method is shown to be able to detect biologically relevant sets as significant, when other methods (including FET) cannot. We also find that the popular GSEA-NR method performs poorly when compared to MAXMEAN-NR. CONCLUSION: MAXMEAN-NR is a method of gene set analysis for experiments with few replicates, as is common for prokaryotes. Results of simulation and real data analysis suggest that the MAXMEAN-NR method offers increased robustness and biological relevance of findings as compared to FET and other methods, while maintaining the nominal type I error rate. |
format | Text |
id | pubmed-2587482 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-25874822008-11-26 Gene set analyses for interpreting microarray experiments on prokaryotic organisms Tintle, Nathan L Best, Aaron A DeJongh, Matthew Van Bruggen, Dirk Heffron, Fred Porwollik, Steffen Taylor, Ronald C BMC Bioinformatics Methodology Article BACKGROUND: Despite the widespread usage of DNA microarrays, questions remain about how best to interpret the wealth of gene-by-gene transcriptional levels that they measure. Recently, methods have been proposed which use biologically defined sets of genes in interpretation, instead of examining results gene-by-gene. Despite a serious limitation, a method based on Fisher's exact test remains one of the few plausible options for gene set analysis when an experiment has few replicates, as is typically the case for prokaryotes. RESULTS: We extend five methods of gene set analysis from use on experiments with multiple replicates, for use on experiments with few replicates. We then use simulated and real data to compare these methods with each other and with the Fisher's exact test (FET) method. As a result of the simulation we find that a method named MAXMEAN-NR, maintains the nominal rate of false positive findings (type I error rate) while offering good statistical power and robustness to a variety of gene set distributions for set sizes of at least 10. Other methods (ABSSUM-NR or SUM-NR) are shown to be powerful for set sizes less than 10. Analysis of three sets of experimental data shows similar results. Furthermore, the MAXMEAN-NR method is shown to be able to detect biologically relevant sets as significant, when other methods (including FET) cannot. We also find that the popular GSEA-NR method performs poorly when compared to MAXMEAN-NR. CONCLUSION: MAXMEAN-NR is a method of gene set analysis for experiments with few replicates, as is common for prokaryotes. Results of simulation and real data analysis suggest that the MAXMEAN-NR method offers increased robustness and biological relevance of findings as compared to FET and other methods, while maintaining the nominal type I error rate. BioMed Central 2008-11-05 /pmc/articles/PMC2587482/ /pubmed/18986519 http://dx.doi.org/10.1186/1471-2105-9-469 Text en Copyright © 2008 Tintle et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Methodology Article Tintle, Nathan L Best, Aaron A DeJongh, Matthew Van Bruggen, Dirk Heffron, Fred Porwollik, Steffen Taylor, Ronald C Gene set analyses for interpreting microarray experiments on prokaryotic organisms |
title | Gene set analyses for interpreting microarray experiments on prokaryotic organisms |
title_full | Gene set analyses for interpreting microarray experiments on prokaryotic organisms |
title_fullStr | Gene set analyses for interpreting microarray experiments on prokaryotic organisms |
title_full_unstemmed | Gene set analyses for interpreting microarray experiments on prokaryotic organisms |
title_short | Gene set analyses for interpreting microarray experiments on prokaryotic organisms |
title_sort | gene set analyses for interpreting microarray experiments on prokaryotic organisms |
topic | Methodology Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2587482/ https://www.ncbi.nlm.nih.gov/pubmed/18986519 http://dx.doi.org/10.1186/1471-2105-9-469 |
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