Abstract
BACKGROUND: Type 2 diabetes mellitus (T2DM) affects approximately 451 million adults globally. In this study, we identified the optimal combination of marker candidates for detecting T2DM using miRNA-Seq data from 95 samples including T2DM and healthy individuals. METHODS: We utilized the genetic algorithm (GA) in the discovery of an optimal miRNA biomarker set. We discovered miRNA subsets consisting of three miRNAs for detecting T2DM by random forest-based GA (miRDM-rfGA) as a feature selection algorithm and created six GA parameter settings and three settings using traditional feature selection methods (F-test and Lasso). We then evaluated the prediction performance to detect T2DM in the miRNA subsets derived from each setting. RESULTS: The miRNA subset in setting 5 using miRDM-rfGA performed the best in detecting T2DM (mean AUROC = 0.92). Target mRNA identification and functional enrichment analysis of the best miRNA subset (hsa-miR-125b-5p, hsa-miR-7-5p, and hsa-let-7b-5p) validated that this combination was involved in T2DM. We also confirmed that the targeted genes were negatively correlated with the clinical variables related to T2DM in the BxD mouse genetic reference population database. CONCLUSIONS: Using GA in miRNA-Seq data, we identified the optimal miRNA biomarker set for T2DM detection. GA can be a useful tool for biomarker discovery and drug-target identification.