Uncovering miRNA-Disease Associations Through Graph Based Neural Network Representations

Background: MicroRNAs (miRNAs) are an important class of non-coding RNAs that regulate gene expression by binding to target mRNAs and influencing cellular processes such as differentiation, proliferation, and apoptosis. Dysregulation in miRNA expression has been reported to be implicated in many human diseases, including cancer, cardiovascular, and neurodegenerative disorders. Identifying disease-related miRNAs is therefore essential for understanding disease mechanisms and supporting biomarker discovery, but time and cost of experimental validation are the main limitations. Methods: We present a graph-based learning framework that models the complex relationships between miRNAs, diseases, and related biological entities within a heterogeneous network. The model employs a message-passing neural architecture to learn structured embeddings from multiple node and edge types, integrating biological priors from curated resources. This network representation enables the inference of novel miRNA-disease associations, even in sparsely annotated regions of the network. The approach was trained and validated on a dataset benchmark using ten replicated experiments to ensure robustness. Results: The method achieved an average AUC-ROC of ~98%, outperforming previously reported computational approaches on the same dataset. Moreover, predictions were consistent across validation folds and robustness analyses were conducted to evaluate stability and highlight the most important information. Conclusions: Integrating heterogeneous biological information and representing it through graph neural network representation learning offers a powerful and generalizable way to predict relevant associations, including miRNA-disease, and provide a robust computational framework to support biomedical discovery and translational research.