Controlling false discoveries in multidimensional directional decisions, with applications to gene expression data on ordered categories.
TLDR
A procedure extending that of Benjamini and Yekutieli based on the Bonferroni test for each gene is developed, and a proof is given for its mdFDR control when the underlying test statistics are independent across the genes.Abstract:
Microarray gene expression studies over ordered categories are routinely conducted to gain insights into biological functions of genes and the underlying biological processes. Some common experiments are time-course/dose-response experiments where a tissue or cell line is exposed to different doses and/or durations of time to a chemical. A goal of such studies is to identify gene expression patterns/profiles over the ordered categories. This problem can be formulated as a multiple testing problem where for each gene the null hypothesis of no difference between the successive mean gene expressions is tested and further directional decisions are made if it is rejected. Much of the existing multiple testing procedures are devised for controlling the usual false discovery rate (FDR) rather than the mixed directional FDR (mdFDR), the expected proportion of Type I and directional errors among all rejections. Benjamini and Yekutieli (2005, Journal of the American Statistical Association 100, 71-93) proved that an augmentation of the usual Benjamini-Hochberg (BH) procedure can control the mdFDR while testing simple null hypotheses against two-sided alternatives in terms of one-dimensional parameters. In this article, we consider the problem of controlling the mdFDR involving multidimensional parameters. To deal with this problem, we develop a procedure extending that of Benjamini and Yekutieli based on the Bonferroni test for each gene. A proof is given for its mdFDR control when the underlying test statistics are independent across the genes. The results of a simulation study evaluating its performance under independence as well as under dependence of the underlying test statistics across the genes relative to other relevant procedures are reported. Finally, the proposed methodology is applied to a time-course microarray data obtained by Lobenhofer et al. (2002, Molecular Endocrinology 16, 1215-1229). We identified several important cell-cycle genes, such as DNA replication/repair gene MCM4 and replication factor subunit C2, which were not identified by the previous analyses of the same data by Lobenhofer et al. (2002) and Peddada et al. (2003, Bioinformatics 19, 834-841). Although some of our findings overlap with previous findings, we identify several other genes that complement the results of Lobenhofer et al. (2002).read more
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References
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Journal ArticleDOI
Controlling the false discovery rate: a practical and powerful approach to multiple testing
Yoav Benjamini,Yosef Hochberg +1 more
TL;DR: In this paper, a different approach to problems of multiple significance testing is presented, which calls for controlling the expected proportion of falsely rejected hypotheses -the false discovery rate, which is equivalent to the FWER when all hypotheses are true but is smaller otherwise.
Journal ArticleDOI
The control of the false discovery rate in multiple testing under dependency
Yoav Benjamini,Daniel Yekutieli +1 more
TL;DR: In this paper, it was shown that a simple FDR controlling procedure for independent test statistics can also control the false discovery rate when test statistics have positive regression dependency on each of the test statistics corresponding to the true null hypotheses.
Journal ArticleDOI
An improved Bonferroni procedure for multiple tests of significance
TL;DR: In this article, a modification of the Bonferroni procedure for testing multiple hypotheses is presented, based on the ordered p-values of the individual tests, which is less conservative than the classical BFP but is still simple to apply.
Journal Article
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TL;DR: In this paper, two major figures in adaptive control provide a wealth of material for researchers, practitioners, and students to enhance their work through the information on many new theoretical developments, and can be used by mathematical control theory specialists to adapt their research to practical needs.
Journal ArticleDOI
On the Adaptive Control of the False Discovery Rate in Multiple Testing With Independent Statistics
Yoav Benjamini,Yosef Hochberg +1 more
TL;DR: Benjamini and Hochberg as discussed by the authors presented an adaptive procedure, where the number of true null hypotheses is estimated first as in Hochgraham and Benjamini (1990), and this estimate is used in the procedure of Benjamine and Hohberg (1995).
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