False discovery rate control in two-stage designs.

BMC Bioinformatics
Sonja Zehetmayer, Martin Posch

Abstract

For gene expression or gene association studies with a large number of hypotheses the number of measurements per marker in a conventional single-stage design is often low due to limited resources. Two-stage designs have been proposed where in a first stage promising hypotheses are identified and further investigated in the second stage with larger sample sizes. For two types of two-stage designs proposed in the literature we derive multiple testing procedures controlling the False Discovery Rate (FDR) demonstrating FDR control by simulations: designs where a fixed number of top-ranked hypotheses are selected and designs where the selection in the interim analysis is based on an FDR threshold. In contrast to earlier approaches which use only the second-stage data in the hypothesis tests (pilot approach), the proposed testing procedures are based on the pooled data from both stages (integrated approach). For both selection rules the multiple testing procedures control the FDR in the considered simulation scenarios. This holds for the case of independent observations across hypotheses as well as for certain correlation structures. Additionally, we show that in scenarios with small effect sizes the testing procedures based on the p...Continue Reading

References

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Aug 11, 2005·Bioinformatics·Sonja ZehetmayerMartin Posch
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Apr 30, 2008·Statistics in Medicine·Sonja ZehetmayerMartin Posch
Mar 2, 2010·Bioinformatics·Sonja Zehetmayer, Martin Posch

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Citations

Jun 14, 2013·Evidence-based Complementary and Alternative Medicine : ECAM·Jiang-Ti KongSean Mackey
Jun 11, 2017·Statistical Applications in Genetics and Molecular Biology·Jakub Pecanka, Jelle Goeman
Nov 9, 2018·American Journal of Physiology. Lung Cellular and Molecular Physiology·Leah R ReznikovKevin Vogt
Nov 6, 2015·Behavior Genetics·Chandra A ReynoldsUNKNOWN Interplay of Genes and Environment across Multiple Studies (IGEMS) consortium
Apr 2, 2019·Statistics in Medicine·Takanori KawabataShigeyuki Matsui

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