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EAMA: Empirically adjusted meta-analysis for large-scale simultaneous hypothesis testing in genomic experiments
Recent developments in high throughput genomic assays have opened up the possibility of testing hundreds and thousands of genes simultaneously. However, adhering to the regular statistical assumptions regarding the null distributions of test statistics in such large-scale multiple testing frameworks...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5663489/ https://www.ncbi.nlm.nih.gov/pubmed/29088275 http://dx.doi.org/10.1371/journal.pone.0187287 |
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author | Sikdar, Sinjini Datta, Somnath Datta, Susmita |
author_facet | Sikdar, Sinjini Datta, Somnath Datta, Susmita |
author_sort | Sikdar, Sinjini |
collection | PubMed |
description | Recent developments in high throughput genomic assays have opened up the possibility of testing hundreds and thousands of genes simultaneously. However, adhering to the regular statistical assumptions regarding the null distributions of test statistics in such large-scale multiple testing frameworks has the potential of leading to incorrect significance testing results and biased inference. This problem gets worse when one combines results from different independent genomic experiments with a possibility of ending up with gross false discoveries of significant genes. In this article, we develop a meta-analysis method of combining p-values from different independent experiments involving large-scale multiple testing frameworks, through empirical adjustments of the individual test statistics and p-values. Even though, it is based on various existing ideas, this specific combination is novel and potentially useful. Through simulation studies and real genomic datasets we show that our method outperforms the standard meta-analysis approach of significance testing in terms of accurately identifying the truly significant set of genes. |
format | Online Article Text |
id | pubmed-5663489 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-56634892017-11-09 EAMA: Empirically adjusted meta-analysis for large-scale simultaneous hypothesis testing in genomic experiments Sikdar, Sinjini Datta, Somnath Datta, Susmita PLoS One Research Article Recent developments in high throughput genomic assays have opened up the possibility of testing hundreds and thousands of genes simultaneously. However, adhering to the regular statistical assumptions regarding the null distributions of test statistics in such large-scale multiple testing frameworks has the potential of leading to incorrect significance testing results and biased inference. This problem gets worse when one combines results from different independent genomic experiments with a possibility of ending up with gross false discoveries of significant genes. In this article, we develop a meta-analysis method of combining p-values from different independent experiments involving large-scale multiple testing frameworks, through empirical adjustments of the individual test statistics and p-values. Even though, it is based on various existing ideas, this specific combination is novel and potentially useful. Through simulation studies and real genomic datasets we show that our method outperforms the standard meta-analysis approach of significance testing in terms of accurately identifying the truly significant set of genes. Public Library of Science 2017-10-31 /pmc/articles/PMC5663489/ /pubmed/29088275 http://dx.doi.org/10.1371/journal.pone.0187287 Text en © 2017 Sikdar et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Sikdar, Sinjini Datta, Somnath Datta, Susmita EAMA: Empirically adjusted meta-analysis for large-scale simultaneous hypothesis testing in genomic experiments |
title | EAMA: Empirically adjusted meta-analysis for large-scale simultaneous hypothesis testing in genomic experiments |
title_full | EAMA: Empirically adjusted meta-analysis for large-scale simultaneous hypothesis testing in genomic experiments |
title_fullStr | EAMA: Empirically adjusted meta-analysis for large-scale simultaneous hypothesis testing in genomic experiments |
title_full_unstemmed | EAMA: Empirically adjusted meta-analysis for large-scale simultaneous hypothesis testing in genomic experiments |
title_short | EAMA: Empirically adjusted meta-analysis for large-scale simultaneous hypothesis testing in genomic experiments |
title_sort | eama: empirically adjusted meta-analysis for large-scale simultaneous hypothesis testing in genomic experiments |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5663489/ https://www.ncbi.nlm.nih.gov/pubmed/29088275 http://dx.doi.org/10.1371/journal.pone.0187287 |
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