Abstract

A growing number of studies have suggested that miRNAs (microRNAs) have associations with human diseases, the design and discovery of drug. But so far, we do not yet fully understand the molecular mechanism of miRNAs in the development of human diseases. Predicting miRNA-disease associations is helpful for understanding the molecular mechanism of miRNAs in the development of human diseases. However, wet-lab experiments are time-consuming and need higher costs to discover miRNA-disease associations. Some computational methods are proposed for predicting miRNA-disease associations, but the prediction performance of these methods needs to be further improved. In this study, we propose a new computational model (KRLSMDA) based on similarity and the Kronecker Regularized Least Squares algorithm. In KRLSMDA, the miRNA functional similarity, the miRNA sequence similarity and the Gaussian Interaction Profile (GIP) kernel similarity are integrated into the comprehensive miRNA similarity. Then we compute the disease semantic similarity, disease functional similarity and the GIP kernel similarity to construct the comprehensive disease similarity based on the disease semantic information, the disease functional information and known miRNA-disease associations, respectively. Finally, the kronecker regularized least squares algorithm is used to predict hidden miRNA-disease associations. The experimental results show that KRLSMDA has achieved the average Area Under the Curve (AUC) values of 0.9181±0.032 and 0.9267±0.022 in 5-fold Cross-Validation (5CV) and 10-fold Cross-Validation (10CV), respectively, which demonstrates KRLSMDA is superior to four competing models. We expect KRLSMDA to be a supplement in the field of biomedical research in the future.

Highlights

  • MicroRNAs are short, single-stranded non-coding RNAs (~22 nt) that can regulate gene expression by base pair binding to the 3' Untranslated Region (UTR) of their messenger RNA (Llave et al, 2002; Eulalio et al, 2008)

  • According to the biological assumption that similar miRNA sin cline to interact with similar diseases, the Gaussian Interaction Profile (GIP) kernel similarity between miRNA mi and miRNA mj is calculated based on the known miRNA-disease associations:

  • Driven by the kronecker regularized least squares algorithm of successful applications, we propose a computational method (KRLSMDA) to predict hidden miRNA-disease associations based on the kronecker regularized least squares algorithm

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Summary

Introduction

MicroRNAs (miRNAs) are short, single-stranded non-coding RNAs (~22 nt) that can regulate gene expression by base pair binding to the 3' Untranslated Region (UTR) of their messenger RNA (mRNA) (Llave et al, 2002; Eulalio et al, 2008). Predicting hidden miRNA-disease associations by biological experiments is time-consuming and expensive. A new computational model (KRLSMDA) is proposed to predict miRNA-disease associations based on the Regularized Least Squares algorithm of Kronecker product kernel. Based on the miRNA functional information, miRNA sequence information and known miRNA-disease associations, KRLSMDA computes the miRNA functional similarity, the miRNA sequence similarity and the Gaussian Interaction Profile (GIP) kernel similarity to construct a comprehensive miRNA similarity matrix by the linear weighted method. We further compute the disease functional similarity and the GIP kernel similarity based on the disease functional information and known miRNA-disease associations, respectively. The kronecker product kernel-based regularized least squares algorithm is applied for predicting the associations scores of miRNA-disease pairs.

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