ECKO: Ensemble of Clustered Knockoffs for Robust Multivariate Inference on fMRI Data

Abstract

Continuous improvement in medical imaging techniques allows the acquisition of higher-resolution images. When these are used in a predictive setting, a greater number of explanatory variables are potentially related to the dependent variable (the response). Meanwhile, the number of acquisitions per experiment remains limited. In such high dimension/small sample size setting, it is desirable to find the explanatory variables that are truly related to the response while controlling the rate of false discoveries. To achieve this goal, novel multivariate inference procedures, such as knockoff inference, have been proposed recently. However, they require the feature covariance to be well-defined, which is impossible in high-dimensional settings. In this paper, we propose a new algorithm, called Ensemble of Clustered Knockoffs, that allows to select explanatory variables while controlling the false discovery rate (FDR), up to a prescribed spatial tolerance. The core idea is that knockoff-based inference can be applied on groups (clusters) of voxels, which drastically reduces the problem’s dimension; an ensembling step then removes the dependence on a fixed clustering and stabilizes the results. We benchmark this algorithm and other FDR-controlling methods on brain imaging datasets and observe empirical gains in sensitivity, while the false discovery rate is controlled at the nominal level.