Abstract

Controlling false discovery rate (FDR) is a powerful approach to multiple testing. In many applications, the tested hypotheses have an inherent hierarchical structure. In this paper, we focus on the fixed sequence structure where the testing order of the hypotheses has been strictly specified in advance. We are motivated to study such a structure, since it is the most basic of hierarchical structure, yet it is often seen in real applications such as statistical process control and streaming data analysis. We first consider a conventional fixed sequence method that stops testing once an acceptance occurs, and develop such a method controlling FDR under both arbitrary and negative dependencies. The method under arbitrary dependency is shown to be unimprovable without losing control of FDR and, unlike existing FDR methods; it cannot be improved even by restricting to the usual positive regression dependence on subset (PRDS) condition. To account for any potential mistakes in the ordering of the tests, we extend the conventional fixed sequence method to one that allows more but a given number of acceptances. Simulation studies show that the proposed procedures can be powerful alternatives to existing FDR controlling procedures. The proposed procedures are illustrated through a real data set from a microarray experiment.

Highlights

  • In many applications of multiple testing, such as genomic research, clinical trials, and statistical process control, the hypotheses are so structured that they are to be tested in a particular sequence

  • We do so by focusing on a structure where the hypotheses have a fixed pre-defined testing order since this is the simplest of hierarchical structures, yet it is often seen in real applications such as clinical trials, statistical process control and streaming data analysis

  • Using some of the techniques developed in this paper, it is possible to develop other types of fixed sequence procedures controlling the false discovery rate (FDR), such as a fallback-type procedure

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Summary

Introduction

In many applications of multiple testing, such as genomic research, clinical trials, and statistical process control, the hypotheses are so structured that they are to be tested in a particular sequence. This structure may be a natural one, as in Goeman and Mansmann (2008), where Gene Ontology imposes a directed acyclic graph structure onto the tested hypotheses, or can be formed by using a data-driven approach for specifying the testing order of the hypotheses, as in Kropf and Lauter (2002), Kropf et al (2004), Westfall et al (2004), Hommel and Kropf (2005), Finos and Farcomeni (2011), etc. That method is shown to control the FDR only under independence

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