Abstract
BackgroundMultiple hypothesis testing is a pervasive problem in genomic data analysis. The conventional Bonferroni method which controls the family-wise error rate is conservative and with low power. The current paradigm is to control the false discovery rate.ResultsWe characterize the variability of the false discovery rate indices (local false discovery rates, q-value and false discovery proportion) using the bootstrapped method. A colon cancer gene-expression data and a visual refractive errors genome-wide association study data are analyzed as demonstration. We found a high variability in false discovery rate controls for typical genomic studies.ConclusionsWe advise researchers to present the bootstrapped standard errors alongside with the false discovery rate indices.Electronic supplementary materialThe online version of this article (doi:10.1186/s12863-015-0259-z) contains supplementary material, which is available to authorized users.
Highlights
Multiple hypothesis testing is a pervasive problem in genomic data analysis
As the unit of analysis for an False discovery rate (FDR) control is a P-value rather than a study subject, we propose a P-value-based bootstrap method to characterize the variability of FDR
We can gauge the variability of the FDR control
Summary
Multiple hypothesis testing is a pervasive problem in genomic data analysis. The conventional Bonferroni method which controls the family-wise error rate is conservative and with low power. The problem of multiple hypothesis testing arises when one compares a large number of genes between different groups (e.g., between breast cancer patients and healthy controls) [1]. In this context, the conventional Bonferroni method which controls the family-wise error rate is conservative and with low power. From a practicing epidemiologist’s viewpoint, the procedure is simple: input the P-values for the genes into an FDR software, get the output of the corresponding q-values [3], and declare a gene significant if its q-value is less than or equal to 0.05 This supposedly ensures the FDR to be controlled at 5 % level
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