Abstract

BackgroundEmerging evidences show that microRNA (miRNA) plays an important role in many human complex diseases. However, considering the inherent time-consuming and expensive of traditional in vitro experiments, more and more attention has been paid to the development of efficient and feasible computational methods to predict the potential associations between miRNA and disease.MethodsIn this work, we present a machine learning-based model called MLMDA for predicting the association of miRNAs and diseases. More specifically, we first use the k-mer sparse matrix to extract miRNA sequence information, and combine it with miRNA functional similarity, disease semantic similarity and Gaussian interaction profile kernel similarity information. Then, more representative features are extracted from them through deep auto-encoder neural network (AE). Finally, the random forest classifier is used to effectively predict potential miRNA–disease associations.ResultsThe experimental results show that the MLMDA model achieves promising performance under fivefold cross validations with AUC values of 0.9172, which is higher than the methods using different classifiers or different feature combination methods mentioned in this paper. In addition, to further evaluate the prediction performance of MLMDA model, case studies are carried out with three Human complex diseases including Lymphoma, Lung Neoplasm, and Esophageal Neoplasms. As a result, 39, 37 and 36 out of the top 40 predicted miRNAs are confirmed by other miRNA–disease association databases.ConclusionsThese prominent experimental results suggest that the MLMDA model could serve as a useful tool guiding the future experimental validation for those promising miRNA biomarker candidates. The source code and datasets explored in this work are available at http://220.171.34.3:81/.

Highlights

  • Emerging evidences show that microRNA plays an important role in many human complex diseases

  • Prediction of miRNA–disease association We make use of fivefold cross validation according to the marked miRNA–disease associations in Human microRNA Disease Database (HMDD) v3.0 to estimate the performance of machine learning for miRNA–disease association prediction (MLMDA)

  • Comparison with different classifier models In order to test the performance of MLMDA model using the Random Forest classifier, we compare it with different classifier models

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Summary

Introduction

Emerging evidences show that microRNA (miRNA) plays an important role in many human complex diseases. In order to further utilize miRNA-target interaction information, Xuan et al built a prediction model named human disease-related miRNA Prediction (HDMP) according to weighted k most semblable node [28]. A prediction method named MIDP using random walk on the network was constructed by Xuan et al [29]. Chen et al developed a prediction model named heterogeneous graph inference for miRNA–disease association prediction (HGIMDA) by mapping confirmed miRNA–disease associations into a heterogeneous graph [30]. Chen et al developed regularized least squares for miRNA–disease association (RLSMDA) which can only use diseases without confirmed miRNAs to discover the association between diseases and miRNAs [31]. A model named ranking-based KNN for miRNA–disease association prediction (RKNNMDA) can predict unconfirmed miRNA without utilizing confirmed miRNAs, built by Chen et al [32]

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