Querying multiple sets of P-values through composed hypothesis testing

Abstract

Motivation: Combining the results of different experiments to exhibit complex patterns or to improve statistical power is a typical aim of data integration. The starting point of the statistical analysis often comes as a set of P-values resulting from previous analyses, that need to be combined flexibly to explore complex hypotheses, while guaranteeing a low proportion of false discoveries.

Results: We introduce the generic concept of composed hypothesis, which corresponds to an arbitrary complex combination of simple hypotheses. We rephrase the problem of testing a composed hypothesis as a classification task and show that finding items for which the composed null hypothesis is rejected boils down to fitting a mixture model and classifying the items according to their posterior probabilities. We show that inference can be efficiently performed and provide a thorough classification rule to control for type I error. The performance and the usefulness of the approach are illustrated in simulations and on two different applications. The method is scalable, does not require any parameter tuning, and provided valuable biological insight on the considered application cases.

Availability and implementation: The QCH methodology is available in the qch package hosted on CRAN. Additionally, R codes to reproduce the Einkorn example are available on the personal webpage of the first author: https://www6.inrae.fr/mia-paris/Equipes/Membres/Tristan-Mary-Huard.

Supplementary information: Supplementary data are available at Bioinformatics online.