The p-filter: multi-layer FDR control for grouped hypotheses

In many practical applications of multiple hypothesis testing using the False Discovery Rate (FDR), the given hypotheses can be naturally partitioned into groups, and one may not only want to control the number of false discoveries (wrongly rejected null hypotheses), but also the number of falsely discovered groups of hypotheses (we say a group is falsely discovered if at least one hypothesis within that group is rejected, when in reality the group contains only nulls). In this paper, we introduce the p-filter, a procedure which unifies and generalizes the standard FDR procedure by Benjamini and Hochberg and global null testing procedure by Simes. We first prove that our proposed method can simultaneously control the overall FDR at the finest level (individual hypotheses treated separately) and the group FDR at coarser levels (when such groups are user-specified). We then generalize the p-filter procedure even further to handle multiple partitions of hypotheses, since that might be natural in many applications. For example, in neuroscience experiments, we may have a hypothesis for every (discretized) location in the brain, and at every (discretized) timepoint: does the stimulus correlate with activity in location x at time t after the stimulus was presented? In this setting, one might want to group hypotheses by location and by time. Importantly, our procedure can handle multiple partitions which are nonhierarchical (i.e. one partition may arrange p-values by voxel, and another partition arranges them by time point; neither one is nested inside the other). We prove that our procedure controls FDR simultaneously across these multiple lay- ers, under assumptions that are standard in the literature: we do not need the hypotheses to be independent, but require a nonnegative dependence condition known as PRDS.