SynerGNet: A Graph Neural Network Model to Predict Anticancer Drug Synergy

Abstract

Drug combination therapy shows promise in cancer treatment by addressing drug resistance, reducing toxicity, and enhancing therapeutic efficacy. However, the intricate and dynamic nature of biological systems makes identifying potential synergistic drugs a costly and time-consuming endeavor. To facilitate the development of combination therapy, techniques employing artificial intelligence have emerged as a transformative solution, providing a sophisticated avenue for advancing existing therapeutic approaches. In this study, we developed SynerGNet, a graph neural network model designed to accurately predict the synergistic effect of drug pairs against cancer cell lines. SynerGNet utilizes cancer-specific featured graphs created by integrating heterogeneous biological features into the human protein–protein interaction network, followed by a reduction process to enhance topological diversity. Leveraging synergy data provided by AZ-DREAM Challenges, the model yields a balanced accuracy of 0.68, significantly outperforming traditional machine learning. Encouragingly, augmenting the training data with carefully constructed synthetic instances improved the balanced accuracy of SynerGNet to 0.73. Finally, the results of an independent validation conducted against DrugCombDB demonstrated that it exhibits a strong performance when applied to unseen data. SynerGNet shows a great potential in detecting drug synergy, positioning itself as a valuable tool that could contribute to the advancement of combination therapy for cancer treatment.

Keywords

• drug combination
• cancer treatment
• graph neural network
• drug synergistic effects
• drug antagonistic effects
• data augmentation