Multiple Testing of One-Sided Hypotheses with Conservative $p$-values

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Main Authors: Seo, Kwangok, Lim, Johan, Choi, Hyungwon, Jeong, Jaesik
Format: Preprint
Published: 2025
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author Seo, Kwangok
Lim, Johan
Choi, Hyungwon
Jeong, Jaesik
author_facet Seo, Kwangok
Lim, Johan
Choi, Hyungwon
Jeong, Jaesik
contents We study a large-scale one-sided multiple testing problem in which test statistics follow normal distributions with unit variance, and the goal is to identify signals with positive mean effects. A conventional approach is to compute $p$-values under the assumption that all null means are exactly zero and then apply standard multiple testing procedures such as the Benjamini-Hochberg (BH) or Storey-BH method. However, because the null hypothesis is composite, some null means may be strictly negative. In this case, the resulting $p$-values are conservative, leading to a substantial loss of power. Existing methods address this issue by modifying the multiple testing procedure itself, for example through conditioning strategies or discarding rules. In contrast, we focus on correcting the $p$-values so that they are exact under the null. Specifically, we estimate the marginal null distribution of the test statistics within an empirical Bayes framework and construct refined $p$-values based on this estimated distribution. These refined $p$-values can then be directly used in standard multiple testing procedures without modification. Extensive simulation studies show that the proposed method substantially improves power when conventional $p$-values are conservative, while achieving comparable performance to existing methods when conventional $p$-values are exact. An application to phosphorylation data further demonstrates the practical effectiveness of our approach.
format Preprint
id arxiv_https___arxiv_org_abs_2512_24588
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle Multiple Testing of One-Sided Hypotheses with Conservative $p$-values
Seo, Kwangok
Lim, Johan
Choi, Hyungwon
Jeong, Jaesik
Methodology
We study a large-scale one-sided multiple testing problem in which test statistics follow normal distributions with unit variance, and the goal is to identify signals with positive mean effects. A conventional approach is to compute $p$-values under the assumption that all null means are exactly zero and then apply standard multiple testing procedures such as the Benjamini-Hochberg (BH) or Storey-BH method. However, because the null hypothesis is composite, some null means may be strictly negative. In this case, the resulting $p$-values are conservative, leading to a substantial loss of power. Existing methods address this issue by modifying the multiple testing procedure itself, for example through conditioning strategies or discarding rules. In contrast, we focus on correcting the $p$-values so that they are exact under the null. Specifically, we estimate the marginal null distribution of the test statistics within an empirical Bayes framework and construct refined $p$-values based on this estimated distribution. These refined $p$-values can then be directly used in standard multiple testing procedures without modification. Extensive simulation studies show that the proposed method substantially improves power when conventional $p$-values are conservative, while achieving comparable performance to existing methods when conventional $p$-values are exact. An application to phosphorylation data further demonstrates the practical effectiveness of our approach.
title Multiple Testing of One-Sided Hypotheses with Conservative $p$-values
topic Methodology
url https://arxiv.org/abs/2512.24588