Abstract

In recent years, accumulating evidences have shown that microRNA (miRNA) plays an important role in the exploration and treatment of diseases, so detection of the associations between miRNA and disease has been drawn more and more attentions. However, traditional experimental methods have the limitations of high cost and time- consuming, a computational method can help us more systematically and effectively predict the potential miRNA-disease associations. In this work, we proposed a novel network embedding-based heterogeneous information integration method to predict miRNA-disease associations. More specifically, a heterogeneous information network is constructed by combining the known associations among lncRNA, drug, protein, disease, and miRNA. After that, the network embedding method Learning Graph Representations with Global Structural Information (GraRep) is employed to learn embeddings of nodes in heterogeneous information network. In this way, the embedding representations of miRNA and disease are integrated with the attribute information of miRNA and disease (e.g. miRNA sequence information and disease semantic similarity) to represent miRNA-disease association pairs. Finally, the Random Forest (RF) classifier is used for predicting potential miRNA-disease associations. Under the 5-fold cross validation, our method obtained 85.11% prediction accuracy with 80.41% sensitivity at the AUC of 91.25%. In addition, in case studies of three major Human diseases, 45 (Colon Neoplasms), 42 (Breast Neoplasms) and 44 (Esophageal Neoplasms) of top-50 predicted miRNAs are respectively verified by other miRNA-disease association databases. In conclusion, the experimental results suggest that our method can be a powerful and useful tool for predicting potential miRNA-disease associations.

Highlights

  • In recent years, accumulating evidences have shown that microRNA plays an important role in the exploration and treatment of diseases, so detection of the associations between miRNA and disease has been drawn more and more attentions

  • It is estimated that 1–4% of the genes in the human genome are miRNAs, with individual miRNAs regulating as many as 200 mRNAs1. miRNA usually binds to the 3′untranslation regions (UTRs) of the target mRNA through sequence-specific base pairs to inhibit the expression of target mRNA2–5

  • We proposed a new method to predict the potential associations between miRNA and disease by extracting the embedding representation of miRNAs and diseases from the heterogeneous information network

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Summary

Introduction

In recent years, accumulating evidences have shown that microRNA (miRNA) plays an important role in the exploration and treatment of diseases, so detection of the associations between miRNA and disease has been drawn more and more attentions. Chen et al.[23] proposed a new bipartite network projection model for predicting potential associations between miRNA and disease (BNPMDA) based on miRNA functional similarity, disease semantic similarity, and the known human miRNA-disease associations. Zheng et al.[24] developed a machine learning-based model for miRNA-disease association prediction (MLMDA) This method uses a deep auto-encoder neural network (AE), disease semantic similarity, miRNA sequence information, miRNA functional similarity and Gaussian association spectrum kernel similarity information to predict potential associations between miRNA and disease. Jiang et al.[27] proposed a calculation method to predict potential miRNA-disease associations by prioritizing the human microRNAome for diseases It is a logical extension of earlier network-based approaches for predicting or prioritizing disease-associated protein-coding genes. A network embedding-based heterogeneous information integration method is proposed to predict the potential associations between miRNA and disease. Our experiments prove that the network embedding method has great potential and provides a new direction for the prediction of miRNA and disease associations

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