Mask-Guided Target Node Feature Learning and Dynamic Detailed Feature Enhancement for lncRNA-Disease Association Prediction

Identifying new relevant long noncoding RNAs (lncRNAs) for various human diseases can facilitate the exploration of the causes and progression of these diseases. Recently, several graph inference methods have been proposed to predict disease-related lncRNAs by exploiting the topological structure and node attributes within graphs. However, these methods did not prioritize the target lncRNA and disease nodes over auxiliary nodes like miRNA nodes, potentially limiting their ability to fully utilize the features of the target nodes. We propose a new method, mask-guided target node feature learning and dynamic detailed feature enhancement for lncRNA-disease association prediction (MDLD), to enhance node feature learning for improved lncRNA-disease association prediction. First, we designed a heterogeneous graph masked transformer autoencoder to guide feature learning, focusing more on the features of target lncRNA (disease) nodes. The target nodes were increasingly masked as training progressed, which helps develop a more robust prediction model. Second, we developed a graph convolutional network with dynamic residuals (GCNDR) to learn and integrate the heterogeneous topology and features of all lncRNA, disease, and miRNA nodes. GCNDR employs an interlayer residual strategy and a residual evolution strategy to mitigate oversmoothing caused by multilayer graph convolution. The interlayer residual strategy estimates the importance of node features learned in the previous GCN encoding layer for nodes in the current encoding layer. Additionally, since there are dependencies in the importance of features of individual lncRNA (disease, miRNA) nodes across multiple encoding layers, a gated recurrent unit-based strategy is proposed to encode these dependencies. Finally, we designed a perspective-level attention mechanism to obtain more informative features of lncRNA and disease node pairs from the perspectives of mask-enhanced and dynamic-enhanced node features. Cross-validation experimental results demonstrated that MDLD outperformed 10 other state-of-the-art prediction methods. Ablation experiments and case studies on candidate lncRNAs for three diseases further proved the technical contributions of MDLD and its capability to discover disease-related lncRNAs.