GNN-SubNet: disease subnetwork detection with explainable graph neural networks.

Abstract

The tremendous success of graphical neural networks (GNNs) already had a major impact on systems biology research. For example, GNNs are currently being used for drug target recognition in protein-drug interaction networks, as well as for cancer gene discovery and more. Important aspects whose practical relevance is often underestimated are comprehensibility, interpretability and explainability. In this work, we present a novel graph-based deep learning framework for disease subnetwork detection via explainable GNNs. Each patient is represented by the topology of a protein-protein interaction (PPI) network, and the nodes are enriched with multi-omics features from gene expression and DNA methylation. In addition, we propose a modification of the GNNexplainer that provides model-wide explanations for improved disease subnetwork detection. The proposed methods and tools are implemented in the GNN-SubNet Python package, which we have made available on our GitHub for the international research community (https://github.com/pievos101/GNN-SubNet). Supplementary data are available at Bioinformatics online.