Abstract

BackgroundIn the process of post-transcription, microRNAs (miRNAs) are closely related to various complex human diseases. Traditional verification methods for miRNA-disease associations take a lot of time and expense, so it is especially important to design computational methods for detecting potential associations. Considering the restrictions of previous computational methods for predicting potential miRNAs-disease associations, we develop the model of FKL-Spa-LapRLS (Fast Kernel Learning Sparse kernel Laplacian Regularized Least Squares) to break through the limitations.ResultFirst, we extract three miRNA similarity kernels and three disease similarity kernels. Then, we combine these kernels into a single kernel through the Fast Kernel Learning (FKL) model, and use sparse kernel (Spa) to eliminate noise in the integrated similarity kernel. Finally, we find the associations via Laplacian Regularized Least Squares (LapRLS). Based on three evaluation methods, global and local leave-one-out cross validation (LOOCV), and 5-fold cross validation, the AUCs of our method achieve 0.9563, 0.8398 and 0.9535, thus it can be seen that our method is reliable. Then, we use case studies of eight neoplasms to further analyze the performance of our method. We find that most of the predicted miRNA-disease associations are confirmed by previous traditional experiments, and some important miRNAs should be paid more attention, which uncover more associations of various neoplasms than other miRNAs.ConclusionsOur proposed model can reveal miRNA-disease associations and improve the accuracy of correlation prediction for various diseases. Our method can be also easily extended with more similarity kernels.

Highlights

  • In the process of post-transcription, microRNAs are closely related to various complex human diseases

  • We demonstrate that the KFL model is more importance than the average kernel method using 10-fold Cross validation (CV) and local leave-one-out cross validation (LOOCV), and the process of sparse kernal has a positive effect on noise elimination in similarity network

  • The Laplacian Regularized Least Squares (LapRLS) method contributes to accuracy of finding potential miRNA-disease associations

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Summary

Introduction

In the process of post-transcription, microRNAs (miRNAs) are closely related to various complex human diseases. In the process of post-transcription, miRNAs are a part of messenger RNA (mRNA) sequences and affect protein synthesis [2,3,4]. Some previous studies have proved that miRNAs are related to various diseases including cancers. Human MicroRNA Disease Database (HMDD) [8] collects 572 miRNAs, 378 Disease and 10368 miRNAdisease associations. The dbDEMC contains of 2224 miRNAs, 36 cancer types and 20037 miRNA-disease associations through the high-throughput methods. These associations promote the development of the computing methods

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