Abstract

BackgroundEvidences have increasingly indicated that lncRNAs (long non-coding RNAs) are deeply involved in important biological regulation processes leading to various human complex diseases. Experimental investigations of these disease associated lncRNAs are slow with high costs. Computational methods to infer potential associations between lncRNAs and diseases have become an effective prior-pinpointing approach to the experimental verification.ResultsIn this study, we develop a novel method for the prediction of lncRNA-disease associations using bi-random walks on a network merging the similarities of lncRNAs and diseases. Particularly, this method applies a Laplacian technique to normalize the lncRNA similarity matrix and the disease similarity matrix before the construction of the lncRNA similarity network and disease similarity network. The two networks are then connected via existing lncRNA-disease associations. After that, bi-random walks are applied on the heterogeneous network to predict the potential associations between the lncRNAs and the diseases. Experimental results demonstrate that the performance of our method is highly comparable to or better than the state-of-the-art methods for predicting lncRNA-disease associations. Our analyses on three cancer data sets (breast cancer, lung cancer, and liver cancer) also indicate the usefulness of our method in practical applications.ConclusionsOur proposed method, including the construction of the lncRNA similarity network and disease similarity network and the bi-random walks algorithm on the heterogeneous network, could be used for prediction of potential associations between the lncRNAs and the diseases.

Highlights

  • MethodsWe downloaded three data sets of Long non-coding RNAs (lncRNAs)-disease associations from the supplementary files of published articles [4, 8], which contains 293 experimentally confirmed lncRNA-disease relationships between 167 diseases and 118 lncRNAs from the LncRNADisease database on October 2012 [4], 454 known lncRNA-disease associations between 162 diseases and 187 lncRNAs from the LncRNADisease database on April 2016, and 594 lncRNA-disease associations between 79 diseases and 310 lncRNAs from the Lnc2Cancer database on July 2016 [8]

  • Evidences have increasingly indicated that Long non-coding RNAs (lncRNAs) are deeply involved in important biological regulation processes leading to various human complex diseases

  • We propose a novel computational model of Laplacian normalization and bi-random walks on heterogeneous networks for predicting lncRNA-disease associations (Lap-BiRWRHLDA)

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Summary

Methods

We downloaded three data sets of lncRNA-disease associations from the supplementary files of published articles [4, 8], which contains 293 experimentally confirmed lncRNA-disease relationships between 167 diseases and 118 lncRNAs from the LncRNADisease database on October 2012 [4], 454 known lncRNA-disease associations between 162 diseases and 187 lncRNAs from the LncRNADisease database on April 2016, and 594 lncRNA-disease associations between 79 diseases and 310 lncRNAs from the Lnc2Cancer database on July 2016 [8]. We downloaded lncRNA expressions and the gene expression levels from the supplementary files of the published articles [4, 8], which contain 21626 expression profiles across 22 human tissues or cell types and 60245 gene expression levels in 16 tissues. Let set L1, where L1 is composed of lncRNAs with lncRNA expression profiles (L1 ⊆ L). The lncRNA expression similarity matrix is represented by matrix SPC, where SPC(l(i), l(j)) is the expression similarity between l(i) and l(j) if they belongs to L1, otherwise 0

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