Abstract

Increasing evidence has revealed that microRNAs (miRNAs) play important roles in the development and progression of human diseases. However, efforts made to uncover OMIM disease-miRNA associations are lacking and the majority of diseases in the OMIM database are not associated with any miRNA. Therefore, there is a strong incentive to develop computational methods to detect potential OMIM disease-miRNA associations. In this paper, random walk on OMIM disease similarity network is applied to predict potential OMIM disease-miRNA associations under the assumption that functionally related miRNAs are often associated with phenotypically similar diseases. Our method makes full use of global disease similarity values. We tested our method on 1226 known OMIM disease-miRNA associations in the framework of leave-one-out cross-validation and achieved an area under the ROC curve of 71.42%. Excellent performance enables us to predict a number of new potential OMIM disease-miRNA associations and the newly predicted associations are publicly released to facilitate future studies. Some predicted associations with high ranks were manually checked and were confirmed from the publicly available databases, which was a strong evidence for the practical relevance of our method.

Highlights

  • MicroRNAs are a class of small noncoding RNAs typically about 22 nucleotides in length

  • The mutation of miRNAs, the dysfunction of miRNA biogenesis, and the dysregulation of miRNAs and their targets may result in various diseases, such as lung cancer [14], lymphoma [15], and breast cancer [16]

  • We propose a computational approach to infer potential human Online Mendelian Inheritance in Man (OMIM) disease-miRNA associations by random walk to prioritize the candidate diseases for miRNAs of interest

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Summary

Introduction

MicroRNAs (miRNAs) are a class of small noncoding RNAs typically about 22 nucleotides in length. They have been identified in eukaryotic organisms ranging from nematodes to humans [1,2,3]. Caenorhabditis elegans (C. elegans) lin-4 and let-7 are the first two discovered miRNAs [4, 5]. MiRNAs normally function as negative regulators of gene expression [6,7,8]. Research reports that miRNAs may act as positive regulators in some cases [9, 10]. Research on the relationship between miRNAs and diseases has become an important biomedical goal

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