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Impact of adaptive filtering on power and false discovery rate in RNA-seq experiments

BACKGROUND: In RNA-sequencing studies a large number of hypothesis tests are performed to compare the differential expression of genes between several conditions. Filtering has been proposed to remove candidate genes with a low expression level which may not be relevant and have little or no chance...

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Autores principales: Zehetmayer, Sonja, Posch, Martin, Graf, Alexandra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9509565/
https://www.ncbi.nlm.nih.gov/pubmed/36153479
http://dx.doi.org/10.1186/s12859-022-04928-z
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author Zehetmayer, Sonja
Posch, Martin
Graf, Alexandra
author_facet Zehetmayer, Sonja
Posch, Martin
Graf, Alexandra
author_sort Zehetmayer, Sonja
collection PubMed
description BACKGROUND: In RNA-sequencing studies a large number of hypothesis tests are performed to compare the differential expression of genes between several conditions. Filtering has been proposed to remove candidate genes with a low expression level which may not be relevant and have little or no chance of showing a difference between conditions. This step may reduce the multiple testing burden and increase power. RESULTS: We show in a simulation study that filtering can lead to some increase in power for RNA-sequencing data, too aggressive filtering, however, can lead to a decline. No uniformly optimal filter in terms of power exists. Depending on the scenario different filters may be optimal. We propose an adaptive filtering strategy which selects one of several filters to maximise the number of rejections. No additional adjustment for multiplicity has to be included, but a rule has to be considered if the number of rejections is too small. CONCLUSIONS: For a large range of simulation scenarios, the adaptive filter maximises the power while the simulated False Discovery Rate is bounded by the pre-defined significance level. Using the adaptive filter, it is not necessary to pre-specify a single individual filtering method optimised for a specific scenario. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12859-022-04928-z.
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spelling pubmed-95095652022-09-26 Impact of adaptive filtering on power and false discovery rate in RNA-seq experiments Zehetmayer, Sonja Posch, Martin Graf, Alexandra BMC Bioinformatics Methodology Article BACKGROUND: In RNA-sequencing studies a large number of hypothesis tests are performed to compare the differential expression of genes between several conditions. Filtering has been proposed to remove candidate genes with a low expression level which may not be relevant and have little or no chance of showing a difference between conditions. This step may reduce the multiple testing burden and increase power. RESULTS: We show in a simulation study that filtering can lead to some increase in power for RNA-sequencing data, too aggressive filtering, however, can lead to a decline. No uniformly optimal filter in terms of power exists. Depending on the scenario different filters may be optimal. We propose an adaptive filtering strategy which selects one of several filters to maximise the number of rejections. No additional adjustment for multiplicity has to be included, but a rule has to be considered if the number of rejections is too small. CONCLUSIONS: For a large range of simulation scenarios, the adaptive filter maximises the power while the simulated False Discovery Rate is bounded by the pre-defined significance level. Using the adaptive filter, it is not necessary to pre-specify a single individual filtering method optimised for a specific scenario. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12859-022-04928-z. BioMed Central 2022-09-24 /pmc/articles/PMC9509565/ /pubmed/36153479 http://dx.doi.org/10.1186/s12859-022-04928-z Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Methodology Article
Zehetmayer, Sonja
Posch, Martin
Graf, Alexandra
Impact of adaptive filtering on power and false discovery rate in RNA-seq experiments
title Impact of adaptive filtering on power and false discovery rate in RNA-seq experiments
title_full Impact of adaptive filtering on power and false discovery rate in RNA-seq experiments
title_fullStr Impact of adaptive filtering on power and false discovery rate in RNA-seq experiments
title_full_unstemmed Impact of adaptive filtering on power and false discovery rate in RNA-seq experiments
title_short Impact of adaptive filtering on power and false discovery rate in RNA-seq experiments
title_sort impact of adaptive filtering on power and false discovery rate in rna-seq experiments
topic Methodology Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9509565/
https://www.ncbi.nlm.nih.gov/pubmed/36153479
http://dx.doi.org/10.1186/s12859-022-04928-z
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