FDR-Corrected Sparse Canonical Correlation Analysis with Applications to Imaging Genomics

TL;DR

This paper introduces an FDR-controlled sparse CCA method for high-dimensional neuroimaging and genomics data, effectively reducing false discoveries while identifying meaningful brain-genome associations.

Contribution

It develops a novel FDR correction technique for sparse CCA that adaptively controls false discoveries in high-dimensional datasets.

Findings

FDR control maintains false discovery rate below target level

Method successfully links brain activity to genomic data

Application reveals meaningful brain-genome associations

Abstract

Reducing the number of false discoveries is presently one of the most pressing issues in the life sciences. It is of especially great importance for many applications in neuroimaging and genomics, where datasets are typically high-dimensional, which means that the number of explanatory variables exceeds the sample size. The false discovery rate (FDR) is a criterion that can be employed to address that issue. Thus it has gained great popularity as a tool for testing multiple hypotheses. Canonical correlation analysis (CCA) is a statistical technique that is used to make sense of the cross-correlation of two sets of measurements collected on the same set of samples (e.g., brain imaging and genomic data for the same mental illness patients), and sparse CCA extends the classical method to high-dimensional settings. Here we propose a way of applying the FDR concept to sparse CCA, and a method to control the FDR. The proposed FDR correction directly influences the sparsity of the solution, adapting it to the unknown true sparsity level. Theoretical derivation as well as simulation studies show that our procedure indeed keeps the FDR of the canonical vectors below a user-specified target level. We apply the proposed method to an imaging genomics dataset from the Philadelphia Neurodevelopmental Cohort. Our results link the brain connectivity profiles derived from brain activity during an emotion identification task, as measured by functional magnetic resonance imaging (fMRI), to the corresponding subjects' genomic data.