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Power analysis for RNA-Seq differential expression studies

BACKGROUND: Sample size calculation and power estimation are essential components of experimental designs in biomedical research. It is very challenging to estimate power for RNA-Seq differential expression under complex experimental designs. Moreover, the dependency among genes should be taken into...

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Detalles Bibliográficos
Autores principales: Yu, Lianbo, Fernandez, Soledad, Brock, Guy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5415728/
https://www.ncbi.nlm.nih.gov/pubmed/28468606
http://dx.doi.org/10.1186/s12859-017-1648-2
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author Yu, Lianbo
Fernandez, Soledad
Brock, Guy
author_facet Yu, Lianbo
Fernandez, Soledad
Brock, Guy
author_sort Yu, Lianbo
collection PubMed
description BACKGROUND: Sample size calculation and power estimation are essential components of experimental designs in biomedical research. It is very challenging to estimate power for RNA-Seq differential expression under complex experimental designs. Moreover, the dependency among genes should be taken into account in order to obtain accurate results. RESULTS: In this paper, we propose a simulation based procedure for power estimation using the negative binomial distribution and assuming a generalized linear model (at the gene level) that considers the dependence between gene expression level and its variance (dispersion) and also allows equal or unequal dispersion across conditions. We compared the performance of both Wald test and likelihood ratio test under different scenarios. The null distribution of the test statistics was simulated for the desired false positive control to avoid excess false positives with the usage of an asymptotic chi-square distribution. We applied this method to the TCGA breast cancer data set. CONCLUSIONS: We provide a framework for power estimation of RNA-Seq data. The proposed procedure is able to properly control the false positive error rate at the nominal level. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12859-017-1648-2) contains supplementary material, which is available to authorized users.
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spelling pubmed-54157282017-05-04 Power analysis for RNA-Seq differential expression studies Yu, Lianbo Fernandez, Soledad Brock, Guy BMC Bioinformatics Methodology Article BACKGROUND: Sample size calculation and power estimation are essential components of experimental designs in biomedical research. It is very challenging to estimate power for RNA-Seq differential expression under complex experimental designs. Moreover, the dependency among genes should be taken into account in order to obtain accurate results. RESULTS: In this paper, we propose a simulation based procedure for power estimation using the negative binomial distribution and assuming a generalized linear model (at the gene level) that considers the dependence between gene expression level and its variance (dispersion) and also allows equal or unequal dispersion across conditions. We compared the performance of both Wald test and likelihood ratio test under different scenarios. The null distribution of the test statistics was simulated for the desired false positive control to avoid excess false positives with the usage of an asymptotic chi-square distribution. We applied this method to the TCGA breast cancer data set. CONCLUSIONS: We provide a framework for power estimation of RNA-Seq data. The proposed procedure is able to properly control the false positive error rate at the nominal level. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12859-017-1648-2) contains supplementary material, which is available to authorized users. BioMed Central 2017-05-03 /pmc/articles/PMC5415728/ /pubmed/28468606 http://dx.doi.org/10.1186/s12859-017-1648-2 Text en © The Author(s) 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Methodology Article
Yu, Lianbo
Fernandez, Soledad
Brock, Guy
Power analysis for RNA-Seq differential expression studies
title Power analysis for RNA-Seq differential expression studies
title_full Power analysis for RNA-Seq differential expression studies
title_fullStr Power analysis for RNA-Seq differential expression studies
title_full_unstemmed Power analysis for RNA-Seq differential expression studies
title_short Power analysis for RNA-Seq differential expression studies
title_sort power analysis for rna-seq differential expression studies
topic Methodology Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5415728/
https://www.ncbi.nlm.nih.gov/pubmed/28468606
http://dx.doi.org/10.1186/s12859-017-1648-2
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