Towards accurate estimation of the proportion of true null hypotheses in multiple testing.

BACKGROUND: Biomedical researchers are now often faced with situations where it is necessary to test a large number of hypotheses simultaneously, eg, in comparative gene expression studies using high-throughput microarray technology. To properly control false positive errors the FDR (false discovery...

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Main Author: Shu-Dong Zhang
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3081301?pdf=render
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author Shu-Dong Zhang
author_facet Shu-Dong Zhang
author_sort Shu-Dong Zhang
collection DOAJ
description BACKGROUND: Biomedical researchers are now often faced with situations where it is necessary to test a large number of hypotheses simultaneously, eg, in comparative gene expression studies using high-throughput microarray technology. To properly control false positive errors the FDR (false discovery rate) approach has become widely used in multiple testing. The accurate estimation of FDR requires the proportion of true null hypotheses being accurately estimated. To date many methods for estimating this quantity have been proposed. Typically when a new method is introduced, some simulations are carried out to show the improved accuracy of the new method. However, the simulations are often very limited to covering only a few points in the parameter space. RESULTS: Here I have carried out extensive in silico experiments to compare some commonly used methods for estimating the proportion of true null hypotheses. The coverage of these simulations is unprecedented thorough over the parameter space compared to typical simulation studies in the literature. Thus this work enables us to draw conclusions globally as to the performance of these different methods. It was found that a very simple method gives the most accurate estimation in a dominantly large area of the parameter space. Given its simplicity and its overall superior accuracy I recommend its use as the first choice for estimating the proportion of true null hypotheses in multiple testing.
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spelling doaj.art-d2f234e23de84247bb25f8dcb4e6ea372022-12-21T19:36:09ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0164e1887410.1371/journal.pone.0018874Towards accurate estimation of the proportion of true null hypotheses in multiple testing.Shu-Dong ZhangBACKGROUND: Biomedical researchers are now often faced with situations where it is necessary to test a large number of hypotheses simultaneously, eg, in comparative gene expression studies using high-throughput microarray technology. To properly control false positive errors the FDR (false discovery rate) approach has become widely used in multiple testing. The accurate estimation of FDR requires the proportion of true null hypotheses being accurately estimated. To date many methods for estimating this quantity have been proposed. Typically when a new method is introduced, some simulations are carried out to show the improved accuracy of the new method. However, the simulations are often very limited to covering only a few points in the parameter space. RESULTS: Here I have carried out extensive in silico experiments to compare some commonly used methods for estimating the proportion of true null hypotheses. The coverage of these simulations is unprecedented thorough over the parameter space compared to typical simulation studies in the literature. Thus this work enables us to draw conclusions globally as to the performance of these different methods. It was found that a very simple method gives the most accurate estimation in a dominantly large area of the parameter space. Given its simplicity and its overall superior accuracy I recommend its use as the first choice for estimating the proportion of true null hypotheses in multiple testing.http://europepmc.org/articles/PMC3081301?pdf=render
spellingShingle Shu-Dong Zhang
Towards accurate estimation of the proportion of true null hypotheses in multiple testing.
PLoS ONE
title Towards accurate estimation of the proportion of true null hypotheses in multiple testing.
title_full Towards accurate estimation of the proportion of true null hypotheses in multiple testing.
title_fullStr Towards accurate estimation of the proportion of true null hypotheses in multiple testing.
title_full_unstemmed Towards accurate estimation of the proportion of true null hypotheses in multiple testing.
title_short Towards accurate estimation of the proportion of true null hypotheses in multiple testing.
title_sort towards accurate estimation of the proportion of true null hypotheses in multiple testing
url http://europepmc.org/articles/PMC3081301?pdf=render
work_keys_str_mv AT shudongzhang towardsaccurateestimationoftheproportionoftruenullhypothesesinmultipletesting