A Dynamic Multi-Scale Hypergraph Learning Framework Driven by Features and Structures for ceRNA-Disease Association Prediction.

Abstract

Competitive endogenous RNA (ceRNA) networks are pivotal for uncovering disease molecular mechanisms. Graph representation learning is a cornerstone for modeling biological regulatory networks and predicting disease-related biomarkers. However, current methods face challenges: traditional graph neural network (GNN) rely on low-order graph structures, which struggle to capture high-order molecular interactions, resulting in topological information loss; shallow GNN fail to model long-range dependencies, while deep architectures suffer from over-smoothing, limiting complex regulatory expression; static embeddings overlook dynamic molecular interactions, reducing biomarker accuracy. These limitations highlight the need for advanced graph learning frameworks. To address these challenges, we propose DMHLF, a Dynamic Multi-scale Hypergraph Learning Framework for predicting disease-associated ceRNA biomarkers. The framework first integrates multiple regulatory relationships among miRNAs, lncRNAs, circRNAs, mRNAs, and diseases to construct disease-specific ceRNA regulatory networks, capturing local and global regulatory patterns through multi-Hop hyperedges. Subsequently, we devise a Hypergraph-Weighted Dynamic Random Walk (HEDRW) method to dynamically extract node meta-embeddings that encode high-order regulatory information. Concurrently, we extend Eigen-GNN spectral analysis to hypergraph structures, incorporating a residual-enhanced hypergraph neural network to preserve the global topological properties of shallow hypergraphs. Finally, a cross-scale attention mechanism aligns and fuses multi-scale features to generate high-quality node embeddings for disease-ceRNA association prediction. Experiments on diverse datasets demonstrate that DMHLF significantly outperforms existing methods. Case study further validates the framework's efficacy in identifying disease-related ceRNA biomarkers, providing a reliable predictive tool for biomedical research.