Network-Based Neighborhood Regression

Abstract

Given the ubiquity of modularity in biological systems, module-level regulation analysis is vital for understanding biological systems across various levels and their dynamics. Current statistical analysis on biological modules predominantly focuses on either detecting the functional modules in biological networks or sub-group regression on the biological features without using the network data. This article proposes a novel network-based neighborhood regression framework whose regression functions depend on both the global community-level information and local connectivity structures among entities. An efficient community-wise least square optimization approach is developed to uncover the strength of regulation among the network modules while enabling asymptotic inference. With random graph theory, we derive non-asymptotic estimation error bounds for the proposed estimator, achieving exact minimax optimality. Unlike the root-n consistency typical in canonical linear regression, our model exhibits linear consistency in the number of nodes n, highlighting the advantage of incorporating neighborhood information. The effectiveness of the proposed framework is further supported by extensive numerical experiments. Application to whole-exome sequencing and RNA-sequencing Autism datasets demonstrates the usage of the proposed method in identifying the association between the gene modules of genetic variations and the gene modules of genomic differential expressions. Supplementary materials for this article are available online, including a standardized description of the materials available for reproducing the work.