M-GNN: A Topology-Enhanced Multi-Modal Graph Neural Network for Cancer Driver Gene Prediction

Background: Accurate identification of cancer driver genes is essential for understanding tumorigenesis and developing targeted therapies. Although graph neural networks (GNNs) have advanced multi-omics integration, existing methods often simply concatenate omics features and underutilize the topological information of biological networks. Methods: We propose M-GNN, a multi-modal GNN framework for cancer driver gene prediction. It employs separate Graph Convolutional Network (GCN) encoders to process four types of omics data (mutation, expression, methylation, copy number variation (CNV)), each represented as a 16-dimensional vector. We incorporate knowledge distillation by using soft labels from a pre-trained teacher model to enhance feature representation. An attention mechanism adaptively fuses the encoded omics features, and a dual-path classifier combining a GCN and a Multilayer Perceptron (MLP) preserves both intrinsic gene properties and network topology. Results: Experiments on three public protein-protein interaction (PPI) networks show that M-GNN consistently achieves the highest or second-highest AUPRC compared to five state-of-the-art methods. Ablation studies confirm the contribution of each module, and biological interpretability analysis-including analysis of GO enrichment and drug sensitivity-validates the reliability of the predicted genes. Conclusions: M-GNN provides a robust and interpretable computational tool for systematic cancer driver gene identification, effectively integrating multi-omics and network data.