Identifying differentially expressed genes using false discovery rate controlling procedures

Anat Reiner*, Daniel Yekutieli, Yoav Benjamini

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1390 Scopus citations

Abstract

Motivation: DNA microarrays have recently been used for the purpose of monitoring expression levels of thousands of genes simultaneously and identifying those genes that are differentially expressed. The probability that a false identification (type I error) is committed can increase sharply when the number of tested genes gets large. Correlation between the test statistics attributed to gene co-regulation and dependency in the measurement errors of the gene expression levels further complicates the problem. In this paper we address this very large multiplicity problem by adopting the false discovery rate (FDR) controlling approach. In order to address the dependency problem, we present three resampling-based FDR controlling procedures, that account for the test statistics distribution, and compare their performance to that of the naiÌve application of the linear step-up procedure in Benjamini and Hochberg (1995). The procedures are studied using simulated microarray data, and their performance is examined relative to their ease of implementation. Results: Comparative simulation analysis shows that all four FDR controlling procedures control the FDR at the desired level, and retain substantially more power then the family-wise error rate controlling procedures. In terms of power, using resampling of the marginal distribution of each test statistics substantially improves the performance over the naiÌve one. The highest power is achieved, at the expense of a more sophisticated algorithm, by the resampling-based procedures that resample the joint distribution of the test statistics and estimate the level of FDR control.

Original languageEnglish
Pages (from-to)368-375
Number of pages8
JournalBioinformatics
Volume19
Issue number3
DOIs
StatePublished - 12 Feb 2003

Funding

FundersFunder number
Israeli Academy of Sciences and Humanities
U.S.–Israel Binational Science Foundation
National Institutes of Health

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