Bayesian pathway analysis over brain network mediators for survival data.

Abstract

Technological advancements in noninvasive imaging facilitate the construction of whole brain interconnected networks, known as brain connectivity. Existing approaches to analyze brain connectivity frequently disaggregate the entire network into a vector of unique edges or summary measures, leading to a substantial loss of information. Motivated by the need to explore the effect mechanism among genetic exposure, brain connectivity, and time to disease onset with maximum information extraction, we propose a Bayesian approach to model the effect pathway between each of these components while quantifying the mediating role of brain networks. To accommodate the biological architectures of brain connectivity constructed along white matter fiber tracts, we develop a structural model which includes a symmetric matrix-variate accelerated failure time model for disease onset and a symmetric matrix response regression for the network-variate mediator. We further impose within-graph sparsity and between-graph shrinkage to identify informative network configurations and eliminate the interference of noisy components. Simulations are carried out to confirm the advantages of our proposed method over existing alternatives. By applying the proposed method to the landmark Alzheimer's Disease Neuroimaging Initiative study, we obtain neurobiologically plausible insights that may inform future intervention strategies.