Abstract
BackgroundMicroRNA (miRNA) plays a key role in regulation mechanism of human biological processes, including the development of disease and disorder. It is necessary to identify potential miRNA biomarkers for various human diseases. Computational prediction model is expected to accelerate the process of identification.ResultsConsidering the limitations of previously proposed models, we present a novel computational model called FMSM. It infers latent miRNA biomarkers involved in the mechanism of various diseases based on the known miRNA-disease association network, miRNA expression similarity, disease semantic similarity and Gaussian interaction profile kernel similarity. FMSM achieves reliable prediction performance in 5-fold and leave-one-out cross validations with area under ROC curve (AUC) values of 0.9629+/− 0.0127 and 0.9433, respectively, which outperforms the state-of-the-art competitors and classical algorithms. In addition, 19 of top 25 predicted miRNAs have been validated to have associations with Colonic Neoplasms in case study.ConclusionsA factored miRNA similarity based model and miRNA expression similarity substantially contribute to the well-performing prediction. The list of the predicted most latent miRNA biomarkers of various human diseases is publicized. It is anticipated that FMSM could serve as a useful tool guiding the future experimental validation for those promising miRNA biomarker candidates.
Highlights
MicroRNA plays a key role in regulation mechanism of human biological processes, including the development of disease and disorder
Leave-one-out and 5-fold cross validation Two validation frameworks, i.e., leave-one-out cross validation (LOOCV) and 5-fold CV were employed to assess the predictive performance of the proposed model based on the known miRNA-disease associations derived from HMDD v2.0 database [29]
Since the proposed model aims to predict the potential miRNA biomarkers for various human diseases, the predictive score of the test sample is only compared with other candidate miRNAs’ in the scope of the same disease
Summary
MicroRNA (miRNA) plays a key role in regulation mechanism of human biological processes, including the development of disease and disorder. MiRNAs primarily get involved in the negative regulation of gene expression. Their mediated regulation plays a key role. In 2009, a study on inhibiting the metastatic nature of breast cancer suggested that five members of the microRNA-200 family are down-regulated in tumor development of breast cancer [23]. These convincing evidences prove that miRNAs could serve as master regulators of gene expression in multiple disease-related signaling pathways. MiRNA signatures or expression levels are emerging as promising biomarkers for disease therapy, diagnosis, prognosis and prevention
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