MGDHGS: Gene-bridged metabolite-disease relationships prediction via GraphSAGE and self-attention mechanism

Metabolites represent the underlying information of biological systems. Revealing the links between metabolites and diseases can facilitate the development of targeted drugs. Traditional biological experiments can be used to validate the relationships of metabolite-disease, but these methods are time-consuming and labor-intensive. In contrast, the prevailing computational methods have improved efficiency but primarily rely on the metabolite-disease interactions, overlooking the impact of other biological components. To remedy the problem, we present a novel computational framework (MGDHGS) based on metabolite-gene-disease heterogeneous network to forecast potential associations. Specifically, we initially integrate data from multiple sources to construct metabolite-gene-disease heterogeneous network that includes known associations and computationally-derived similarities. Then, the GraphSAGE is harnessed to learn the low dimensional neighborhood representation in the heterogeneous network and self-attention mechanism is applied to effectively capture the connectivity patterns, which contributions to combine with nodes intrinsic and extrinsic features. Finally, the ultimate relationships probability scores are predicted by linear regression based on the these characteristics. The five-fold cross-validation showcases impressive AUC (0.9734) and PR (0.9718) for MGDHGS compared with five state-of-the-art methods, and the case studies validate that the metabolite-disease associations predicted by MGDHGS can be substantiated through pertinent biological experiments. The findings of this study show great potential contribution in the development of targeted drugs as well as offering solid support for our understanding of the complex interactions between metabolites, genes and diseases.