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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...

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Detalles Bibliográficos
Autores principales: Sikdar, Sinjini, Datta, Somnath, Datta, Susmita
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
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.
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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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