Single-index modulated multiple testing

TL;DR

This paper introduces a novel multiple testing procedure that leverages prior information through a bivariate p-value, projecting it onto a single index to improve detection power while controlling the false discovery rate.

Contribution

It proposes a new SIM multiple testing method that optimally projects bivariate p-values to enhance power and FDR control in large-scale testing scenarios.

Findings

Significantly improves detection power over existing methods.

Effectively controls false discovery rate in simulations.

Demonstrates practical utility on real dataset.

Abstract

In the context of large-scale multiple testing, hypotheses are often accompanied with certain prior information. In this paper, we present a single-index modulated (SIM) multiple testing procedure, which maintains control of the false discovery rate while incorporating prior information, by assuming the availability of a bivariate $p$-value, $(p_1,p_2)$, for each hypothesis, where $p_1$ is a preliminary $p$-value from prior information and $p_2$ is the primary $p$-value for the ultimate analysis. To find the optimal rejection region for the bivariate $p$-value, we propose a criteria based on the ratio of probability density functions of $(p_1,p_2)$ under the true null and nonnull. This criteria in the bivariate normal setting further motivates us to project the bivariate $p$-value to a single-index, $p(\theta)$, for a wide range of directions $\theta$. The true null distribution of $p(\theta)$ is estimated via parametric and nonparametric approaches, leading to two procedures for estimating and controlling the false discovery rate. To derive the optimal projection direction $\theta$, we propose a new approach based on power comparison, which is further shown to be consistent under some mild conditions. Simulation evaluations indicate that the SIM multiple testing procedure improves the detection power significantly while controlling the false discovery rate. Analysis of a real dataset will be illustrated.