Prediction of circRNA–Disease Associations via Graph Isomorphism Transformer and Dual-Stream Neural Predictor

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Circular RNAs (circRNAs) have attracted increasing attention for their roles in human diseases, making the prediction of circRNA–disease associations (CDAs) a critical research area for advancing disease diagnosis and treatment. However, traditional experimental methods for exploring CDAs are time-consuming and resource-intensive, while existing computational models often struggle with the sparsity of CDA data and fail to uncover potential associations effectively. To address these challenges, we propose a novel CDA prediction method named the Graph Isomorphism Transformer with Dual-Stream Neural Predictor (GIT-DSP), which leverages knowledge graph technology to address data sparsity and predict CDAs more effectively. Specifically, the model incorporates multiple associations between circRNAs, diseases, and other non-coding RNAs (e.g., lncRNAs, and miRNAs) to construct a multi-source heterogeneous knowledge graph, thereby expanding the scope of CDA exploration. Subsequently, a Graph Isomorphism Transformer model is proposed to fully exploit both local and global association information within the knowledge graph, enabling deeper insights into potential CDAs. Furthermore, a Dual-Stream Neural Predictor is introduced to accurately predict complex circRNA–disease associations in the knowledge graph by integrating dual-stream predictive features. Experimental results demonstrate that GIT-DSP outperforms existing state-of-the-art models, offering valuable insights for precision medicine and disease-related research.