A Graph-Informed Modeling Framework Empowering Gene Pathway Discovery

Abstract This study introduces a novel graph-informed modeling framework for improving the statistical analysis of gene expression data, particularly in the context of identifying differentially expressed gene pathways and gene expression-assisted disease classification in a high-dimensional data setting. By integrating gene regulatory network information into hypothesis testing for the difference between mean vectors and linear discriminant analysis, we aim to effectively capture and utilize previously validated external gene interaction information. Our method leverages a block-coordinate descent approach which enables us to incorporate mixed graph information into linear structural equation modeling, accommodating directed/undirected edges and potential cycles in gene regulatory networks. Extensive simulations under various data scenarios have demonstrated the effectiveness of our approach with improved power for gene pathway tests and disease classification over existing methods. An application to a lung cancer dataset from the Cancer Genome Atlas Program (TCGA) further exemplifies the potential of our graph-informed approach in empowering the detection of differentially expressed gene pathways and gene expression-based classification of different lung cancer stages. Our findings underscore the potential utility of incorporating gene regulatory network information in gene pathway analysis, setting the stage for future advancements in gene pathway discovery, disease diagnosis, and treatment strategies. Competing Interest Statement The authors have declared no competing interest.