Integrative Graph-Based Framework for Predicting circRNA Drug Resistance Using Disease Contextualization and Deep Learning

Circular RNAs (circRNAs) play a crucial role in gene regulation and have been implicated in the development of drug resistance in cancer, representing a significant challenge in oncological therapeutics. Despite advancements in computational models predicting RNA-drug interactions, existing frameworks often overlook the complex interplay between circRNAs, drug mechanisms, and disease contexts. This study aims to bridge this gap by introducing a novel computational model, circRDRP, that enhances prediction accuracy by integrating disease-specific contexts into the analysis of circRNA-drug interactions. It employs a hybrid graph neural network that combines features from Graph Attention Networks (GAT) and Graph Convolutional Networks (GCN) in a two-layer structure, with further enhancement through convolutional neural networks. This approach allows for sophisticated feature extraction from integrated networks of circRNAs, drugs, and diseases. Our results demonstrate that the circRDRP model outperforms existing models in predicting drug resistance, showing significant improvements in accuracy, precision, and recall. Specifically, the model shows robust predictive capability in case studies involving major anticancer drugs such as Cisplatin and Methotrexate, indicating its potential utility in precision medicine. In conclusion, circRDRP offers a powerful tool for understanding and predicting drug resistance mediated by circRNAs, with implications for designing more effective cancer therapies.