GNN4DM: A Graph Neural Network-based method to identify overlapping functional disease modules

Abstract

MotivationIdentifying disease modules within molecular interaction networks is an essential exploratory step in computational biology, offering insights into disease mechanisms and potential therapeutic targets. Traditional methods often struggle with the inherent complexity and overlapping nature of biological networks, and they are limited in effectively leveraging the vast amount of available genomic data and biological knowledge. This limitation underscores the need for more effective, automated approaches to integrate these rich data sources. ResultsIn this work, we propose GNN4DM, a novel graph neural network-based structured model that automates the discovery of overlapping functional disease modules. GNN4DM effectively integrates network topology with genomic data to learn the representations of the genes corresponding to functional modules and align these with known biological pathways for enhanced interpretability. Following the DREAM benchmark evaluation setting and extending with three independent data sources (GWAS Atlas, FinnGen, and DisGeNET), we show that GNN4DM performs better than several state-of-the-art methods in detecting biologically meaningful modules. Furthermore, we highlight the methods applicability through its discovery of two novel multimorbidity-modules significantly enriched in a wide array of apparently unrelated diseases. Availability and ImplementationSource code, all training data, and all identified disease modules are freely available for download at https://github.com/gezsi/gnn4dm. GNN4DM was implemented in Python. Contactgezsi.andras@vik.bme.hu