Synchronous Mutual Learning Network and Asynchronous Multi-Scale Embedding Network for miRNA-Disease Association Prediction.

MicroRNA (miRNA) serves as a pivotal regulator of numerous cellular processes, and the identification of miRNA-disease associations (MDAs) is crucial for comprehending complex diseases. Recently, graph neural networks (GNN) have made significant advancements in MDA prediction. However, these methods tend to learn one type of node representation from a single heterogeneous network, ignoring the importance of multiple network topologies and node attributes. Here, we propose SMDAP (Sequence hierarchical modeling-based Mirna-Disease Association Prediction framework), a novel GNN-based framework that incorporates multiple network topologies and various node attributes including miRNA seed and full-length sequences to predict potential MDAs. Specifically, SMDAP consists of two types of MDA representation: following a heterogeneous pattern, we construct a transfer learning-like synchronous mutual learning network to learn the first MDA representation in conjunction with the miRNA seed sequence. Meanwhile, following a homogeneous pattern, we design a subgraph-inspired asynchronous multi-scale embedding network to obtain the second MDA representation based on the miRNA full-length sequence. Subsequently, an adaptive fusion approach is designed to combine the two branches such that we can score the MDAs by the downstream classifier and infer novel MDAs. Comprehensive experiments demonstrate that SMDAP integrates the advantages of multiple network topologies and node attributes into two branch representations. Moreover, the area under the receiver operating characteristic curve is 0.9622 on DB1, which is a 5.06% increase from the baselines. The area under the precision-recall curve is 0.9777, which is a 7.33% increase from the baselines. In addition, case studies on three human cancers validated the predictive performance of SMDAP. Overall, SMDAP represents a powerful tool for MDA prediction.