scholarly journals Resampling-Based Empirical Bayes Multiple Testing Procedures for Controlling Generalized Tail Probability and Expected Value Error Rates: Focus on the False Discovery Rate and Simulation Study

2008 ◽  
Vol 50 (5) ◽  
pp. 716-744 ◽  
Author(s):  
Sandrine Dudoit ◽  
Houston N. Gilbert ◽  
Mark J. van der Laan
2006 ◽  
Vol 04 (05) ◽  
pp. 1057-1068 ◽  
Author(s):  
XING QIU ◽  
ANDREI YAKOVLEV

Some extended false discovery rate (FDR) controlling multiple testing procedures rely heavily on empirical estimates of the FDR constructed from gene expression data. Such estimates are also used as performance indicators when comparing different methods for microarray data analysis. The present communication shows that the variance of the proposed estimators may be intolerably high, the correlation structure of microarray data being the main cause of their instability.


Author(s):  
Gerwyn H Green ◽  
Peter J. Diggle

Multiple testing procedures are commonly used in gene expression studies for the detection of differential expression, where typically thousands of genes are measured over at least two experimental conditions. Given the need for powerful testing procedures, and the attendant danger of false positives in multiple testing, the False Discovery Rate (FDR) controlling procedure of Benjamini and Hochberg (1995) has become a popular tool. When simultaneously testing hypotheses, suppose that R rejections are made, of which Fp are false positives. The Benjamini and Hochberg procedure ensures that the expectation of Fp/R is bounded above by some pre-specified proportion. In practice, the procedure is applied to a single experiment. In this paper we investigate the across-experiment variability of the proportion Fp/R as a function of three experimental parameters. The operational characteristics of the procedure when applied to dependent hypotheses are also considered.


2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Dongmei Li ◽  
Timothy D. Dye

Resampling-based multiple testing procedures are widely used in genomic studies to identify differentially expressed genes and to conduct genome-wide association studies. However, the power and stability properties of these popular resampling-based multiple testing procedures have not been extensively evaluated. Our study focuses on investigating the power and stability of seven resampling-based multiple testing procedures frequently used in high-throughput data analysis for small sample size data through simulations and gene oncology examples. The bootstrap single-step minPprocedure and the bootstrap step-down minPprocedure perform the best among all tested procedures, when sample size is as small as 3 in each group and either familywise error rate or false discovery rate control is desired. When sample size increases to 12 and false discovery rate control is desired, the permutation maxTprocedure and the permutation minPprocedure perform best. Our results provide guidance for high-throughput data analysis when sample size is small.


2004 ◽  
Vol 3 (1) ◽  
pp. 1-69 ◽  
Author(s):  
Sandrine Dudoit ◽  
Mark J. van der Laan ◽  
Katherine S. Pollard

The present article proposes general single-step multiple testing procedures for controlling Type I error rates defined as arbitrary parameters of the distribution of the number of Type I errors, such as the generalized family-wise error rate. A key feature of our approach is the test statistics null distribution (rather than data generating null distribution) used to derive cut-offs (i.e., rejection regions) for these test statistics and the resulting adjusted p-values. For general null hypotheses, corresponding to submodels for the data generating distribution, we identify an asymptotic domination condition for a null distribution under which single-step common-quantile and common-cut-off procedures asymptotically control the Type I error rate, for arbitrary data generating distributions, without the need for conditions such as subset pivotality. Inspired by this general characterization of a null distribution, we then propose as an explicit null distribution the asymptotic distribution of the vector of null value shifted and scaled test statistics. In the special case of family-wise error rate (FWER) control, our method yields the single-step minP and maxT procedures, based on minima of unadjusted p-values and maxima of test statistics, respectively, with the important distinction in the choice of null distribution. Single-step procedures based on consistent estimators of the null distribution are shown to also provide asymptotic control of the Type I error rate. A general bootstrap algorithm is supplied to conveniently obtain consistent estimators of the null distribution. The special cases of t- and F-statistics are discussed in detail. The companion articles focus on step-down multiple testing procedures for control of the FWER (van der Laan et al., 2004b) and on augmentations of FWER-controlling methods to control error rates such as tail probabilities for the number of false positives and for the proportion of false positives among the rejected hypotheses (van der Laan et al., 2004a). The proposed bootstrap multiple testing procedures are evaluated by a simulation study and applied to genomic data in the fourth article of the series (Pollard et al., 2004).


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