Covariance Matrix Estimation for High-Throughput Biomedical Data with Interconnected Communities

Estimating a covariance matrix is central to high-dimensional data analysis. Empirical analyses of high-dimensional biomedical data, including genomics, proteomics, microbiome, and neuroimaging, among others, consistently reveal strong modularity in the dependence patterns. In these analyses, intercorrelated high-dimensional biomedical features often form communities or modules that can be interconnected with others. While the interconnected community structure has been extensively studied in biomedical research (e.g., gene co-expression networks), its potential to assist in the estimation of covariance matrices remains largely unexplored. To address this gap, we propose a procedure that leverages the commonly observed interconnected community structure in high-dimensional biomedical data to estimate large covariance and precision matrices. We derive the uniformly minimum-variance unbiased estimators for covariance and precision matrices in closed forms and provide theoretical results on their asymptotic properties. Our proposed method enhances the accuracy of covariance- and precision-matrix estimation and demonstrates superior performance compared to the competing methods in both simulations and real data analyses.