Predicting miRNA-Disease Associations Based on Spectral Graph Transformer with Dynamic Attention and Regularization

Extensive research indicates that microRNAs (miRNAs) play a crucial role in the analysis of complex human diseases. Recently, numerous methods utilizing graph neural networks have been developed to investigate the complex relationships between miRNAs and diseases. However, these methods often face challenges in terms of overall effectiveness and are sensitive to node positioning. To address these issues, the researchers introduce DARSFormer, an advanced deep learning model that integrates dynamic attention mechanisms with a spectral graph Transformer effectively. In the DARSFormer model, a miRNA-disease heterogeneous network is constructed initially. This network undergoes spectral decomposition into eigenvalues and eigenvectors, with the eigenvalue scalars being mapped into a vector space subsequently. An orthogonal graph neural network is employed to refine the parameter matrix. The enhanced features are then input into a graph Transformer, which utilizes a dynamic attention mechanism to amalgamate features by aggregating the enhanced neighbor features of miRNA and disease nodes. A projection layer is subsequently utilized to derive the association scores between miRNAs and diseases. The performance of DARSFormer in predicting miRNA-disease associations (MDAs) is exemplary. It achieves an AUC of 94.18% in a five-fold cross-validation on the HMDD v2.0 database. Similarly, on HMDD v3.2, it records an AUC of 95.27%. Case studies involving colorectal, esophageal, and prostate tumors confirm 27, 28, and 26 of the top 30 associated miRNAs against the dbDEMC and miR2Disease databases, respectively.