A Fast Screening Approach for High-dimensional Outcomes and High-dimensional Predictors

Modeling interactions among multimodal, high-dimensional data is intrinsically challenging due to ultra-high dimensionality and complex dependence structure with high level noise. Screening methods are effective for reducing dimensionality, but most existing approaches shrink only the predictor space while retaining all outcomes. In cross-modal analyses, different outcomes often select different predictor subsets, so the union remains large and the response dimension is unchanged, limiting the practical benefit of screening. This gives rise to heavy computational burdens and poor interpretability. To address these limitations, we propose a new screening framework, Graph Independence Dual Screening (GIDS), which simultaneously reduces the dimensionality of response variables and predictors. We design computationally efficient algorithms that facilitate downstream selection procedures, improving accuracy and scalability, and establish supporting theoretical results. Extensive simulation studies demonstrate that GIDS outperforms existing methods that screen only predictors. To illustrate its utility, we applied GIDS to the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset, analyzing interactions between genome-wide 865,353 DNA methylation and 49,386 transcriptomic variables. GIDS reduced the feature space to approximately 9,000 CpGs and 2,000 transcripts, uncovering blockwise interaction structures: clusters of CpG sites and gene transcripts with strong associations. These findings not only improve computational tractability but also yield interpretable biological insights, highlighting coordinated regulatory mechanisms underlying Alzheimer's disease.

Graph Canonical Correlation Analysis

Canonical correlation analysis (CCA) is a widely used technique for estimating associations between two sets of multi-dimensional variables. Recent advancements in CCA methods have expanded their application to decipher the interactions of multiomics datasets, imaging-omics datasets, and more. However, conventional CCA methods are limited in their ability to incorporate structured patterns in the cross-correlation matrix, potentially leading to suboptimal estimations. To address this limitation, we propose the graph Canonical Correlation Analysis (gCCA) approach, which calculates canonical correlations based on the graph structure of the cross-correlation matrix between the two sets of variables. We develop computationally efficient algorithms for gCCA, and provide theoretical results for finite sample analysis of best subset selection and canonical correlation estimation by introducing concentration inequalities and stopping time rule based on martingale theories. Extensive simulations demonstrate that gCCA outperforms competing CCA methods. Additionally, we apply gCCA to a multiomics dataset of DNA methylation and RNA-seq transcriptomics, identifying both positively and negatively regulated gene expression pathways by DNA methylation pathways.