KGLGANSynergy: knowledge graph-based local and global attention network for drug synergy prediction.

backgroundDrug combination therapy offers an effective strategy for treating complex diseases by leveraging synergistic multi-target effects. However, conventional experimental approaches for identifying synergistic drug pairs are costly and inefficient. Graph representation learning has shown strong potential for modeling complex biomolecular interactions and is widely applied to drug synergy prediction. Despite this progress, existing knowledge graph-based methods primarily focus on node-level relational features while overlooking edge attributes and global semantic context, limiting predictive capability.

methodsWe propose KGLGANSynergy, a knowledge graph-based deep learning framework for drug synergy prediction. The model integrates a Local Graph Attention Network (LGAT) to learn fine-grained neighborhood features as local features, and a Global Graph Attention Network (GGAT) to capture global structural information in the drug knowledge graph as global features. These learned features are fused through a Mutual Cross Attention (MCA) mechanism to obtain representations of drugs and cell lines. The final synergy score is computed by combining the feature vectors of the two drugs and the cell line and applying a sigmoid function to generate the predicted probability.

resultsExperimental results on two benchmark datasets, DrugCombDB and Oncology-Screen, demonstrate that KGLGANSynergy achieves AUPR scores of 0.9360 and 0.9472, respectively, outperforming existing baselines. Case studies further validate the model's ability to accurately identify novel synergistic drug combinations.

conclusionThis study provides a more accurate computational tool for predicting drug synergy and introduces a multi-level graph representation learning paradigm, offering new perspectives for biomedical data modeling and showing considerable potential for clinical applications.