Graph Neural Networks-Based Prediction of Drug Gene Interactions of RTK-VEGF4 Receptor Family in Periodontal Regeneration

Background: The RTK-VEGF4 receptor family, which includes VEGFR-1, VEGFR-2, and VEGFR-3, plays a crucial role in tissue regeneration by promoting angiogenesis, the formation of new blood vessels, and recruiting stem cells and immune cells. Machine learning, particularly graph neural networks (GNNs), has shown high accuracy in predicting these interactions. This study aims to predict drug-gene interactions of the RTK-VEGF4 receptor family in periodontal regeneration using graph neural networks. Material and Methods: The study utilized a dataset comprising 19, 154 drug-gene interactions to analyze the relationships between drugs and protein-coding genes. The dataset was split into training and testing sets, with 80% of the data used for training and 20% for testing. Cytoscape, an open-source software platform, was employed to visualize and analyze the drug-gene interaction network, and CytoHubba, a plugin, was used to identify highly connected nodes. Topological measures were applied to determine the influence and importance of each node. GNNs were used to manage the complex relationships and dependencies within the graphs. Results: The drug-gene interaction network, comprising 815 nodes and 13, 436 edges, was found to be complex and highly interconnected. It was divided into 11 components, displaying low density and heterogeneity, indicative of a sparse structure. The GNN model achieved 97% accuracy in predicting interaction types, including single protein interactions and protein complex groups. Conclusions: The study demonstrates that graph neural networks outperform traditional machine learning methods in predicting drug-gene interactions within the RTK-VEGF protein family in periodontal regeneration, highlighting their potential in advancing therapeutic strategies and drug discovery.