BIM-Ken: Identifying Disease-Related miRNA Biomarkers Based on Knowledge-Enhanced Bio-Network

The identification of microRNA (miRNA) biomarkers is crucial in advancing disease research and improving diagnostic precision. Network-based analysis methods are powerful for identifying disease-related biomarkers. However, it is a challenge to generate a robust molecular network that can accurately reflect miRNA interactions and define reliable miRNA biomarkers. To tackle this issue, we propose a disease-related miRNA biomarker identification method based on the knowledge-enhanced bio-network (BIM-Ken) by combining the miRNA expression data and prior knowledge. BIM-Ken constructs the miRNA cooperation network by examining the miRNA interactions based on the miRNA expression data, which contains characteristics about the specific disease, and the information of the network nodes (miRNAs) is enriched by miRNA knowledge (i.e., miRNA-disease associations) from databases. Further, BIM-Ken optimizes the miRNA cooperation network using the well-designed GAE (graph auto-encoder). We improve the loss function by introducing the functional consistency and the difference prompt, so as to facilitate the optimized network to keep the intrinsically important characteristics of the miRNA data about the specific disease and the prior knowledge. The experimental results on the public datasets showed the superiority of BIM-Ken in classification. Subsequently, BIM-Ken was applied to analyze renal cell carcinoma data, and the defined key modules demonstrated involvement in the cancer-related pathways with good discrimination ability.