EAAI Journal 2026 Journal Article
Adaptive dynamic training heterogeneous graph attention neural network for microRNA-disease association prediction and analysis framework
- Yinbo Liu
- Sijian Wen
- Qi Wu
- Yue Yi
- Yongmei Wang
- Xiaolei Zhu
Accurately predicting microRNA-disease associations (MDAs) is crucial for identifying biomarkers and therapeutic targets in complex diseases. However, experimental validation is costly, and existing computational methods, particularly Graph Neural Networks (GNNs), are limited by data sparsity. In such sparse graphs, the lack of topological connections hinders effective message passing, leading to poor performance for isolated nodes and in cold-start scenarios. To address these challenges, we propose the adaptive dynamic heterogeneous graph attention neural network (ADHGMDA), a framework for MDAs prediction and analysis. First, to resolve connectivity issues, we construct a dual-layer heterogeneous graph enhanced with virtual nodes derived via K-means clustering. These virtual nodes act as semantic bridges, integrating isolated microRNAs and diseases into the network. Second, we introduce a dynamic feature learning mechanism that simulates data sparsity during training, forcing the model to learn robust representations for cold-start prediction. Third, to mitigate the over-smoothing common in deep GNNs, we design a gradient conflict-aware multi-task optimization strategy with dynamic weight adaptation. Furthermore, addressing the issue that existing benchmarks rely on outdated data, we reconstructed a benchmark dataset based on the latest databases, integrated with visualization tools. Experimental results demonstrate that ADHGMDA significantly outperforms seven state-of-the-art methods, achieving area under the receiver operating characteristic curve scores of 0. 9698 and 0. 9730. In case studies on herpes simplex and interstitial nephritis, the model exhibits excellent performance in uncovering potential pathogenic pathways. Meanwhile, extensive validation experiments confirm that it has good robustness against label noise, class imbalance, and the cold-start problem of isolated nodes.