Motivation 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. Results 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 …