In search of the ratio of miRNA expression as robust biomarkers for constructing stable diagnostic models among...

MicroRNAs (miRNAs) are promising biomarkers for the early detection of disease, and many miRNA-based diagnostic models have been constructed to distinguish patients and healthy individuals. To thoroughly utilize the miRNA-profiling data across different sequencing platforms or multiple centers, the models accounting the batch effects were demanded for the generalization of medical application. We conducted transcription factor (TF)-mediated miRNA-miRNA interaction network analysis and adopted the within-sample expression ratios of miRNA pairs as predictive markers. The ratio of the expression values between each miRNA pair turned out to be stable across multiple data sources. A genetic algorithm-based classifier was constructed to quantify risk scores of the probability of disease and discriminate disease states from normal states in discovery, with a validation dataset for COVID-19, renal cell carcinoma, and lung adenocarcinoma. The predictive models based on the expression ratio of interacting miRNA pairs demonstrated good performances in the discovery and validation datasets, and the classifier may be used accurately for the early detection of disease.