Weighted mining of massive collections of $p$-values by convex optimization

TL;DR

Princessp is a convex optimization-based method for weighted multiple testing that allows prioritization and constraints, scalable to large datasets, with applications demonstrated in genomics.

Contribution

Introduces Princessp, a convex optimization framework for weighted multiple testing with constraints, enabling exact solutions in cases previously considered nonconvex.

Findings

Scales to massive datasets in genomics.

Allows exact solutions for monotone likelihood ratio families.

Outperforms standard methods in application examples.

Abstract

Researchers in data-rich disciplines---think of computational genomics and observational cosmology---often wish to mine large bodies of $p$-values looking for significant effects, while controlling the false discovery rate or family-wise error rate. Increasingly, researchers also wish to prioritize certain hypotheses, for example those thought to have larger effect sizes, by upweighting, and to impose constraints on the underlying mining, such as monotonicity along a certain sequence. We introduce Princessp, a principled method for performing weighted multiple testing by constrained convex optimization. Our method elegantly allows one to prioritize certain hypotheses through upweighting and to discount others through downweighting, while constraining the underlying weights involved in the mining process. When the $p$-values derive from monotone likelihood ratio families like the Gaussian means model, the new method allows exact solution of an important optimal weighting problem previously thought to be nonconvex and computationally infeasible. Our method scales to massive dataset sizes. We illustrate the applications of Princessp on a series of standard genomics datasets and offer comparisons with several previous `standard' methods. Princessp offers both ease of operation and the ability to scale to extremely large problem sizes. The method is available as open-source software from http://github.com/dobriban/pvalue_weighting_matlab .