Abstract

An increasing number of studies have indicated that long-non-coding RNAs (lncRNAs) play crucial roles in biological processes, complex disease diagnoses, prognoses, and treatments. However, experimentally validated associations between lncRNAs and diseases are still very limited. Recently, computational models have been developed to discover potential associations between lncRNAs and diseases by integrating multiple heterogeneous biological data; this has become a hot topic in biological research. In this article, we constructed a global tripartite network by integrating a variety of biological information including miRNA–disease, miRNA–lncRNA, and lncRNA–disease associations and interactions. Then, we constructed a global quadruple network by appending gene–lncRNA interaction, gene–disease association, and gene–miRNA interaction networks to the global tripartite network. Subsequently, based on these two global networks, a novel approach was proposed based on the naïve Bayesian classifier to predict potential lncRNA–disease associations (NBCLDA). Comparing with the state-of-the-art methods, our new method does not entirely rely on known lncRNA–disease associations, and can achieve a reliable performance with effective area under ROC curve (AUCs)in leave-one-out cross validation. Moreover, in order to further estimate the performance of NBCLDA, case studies of colorectal cancer, prostate cancer, and glioma were implemented in this paper, and the simulation results demonstrated that NBCLDA can be an excellent tool for biomedical research in the future.

Highlights

  • Long non-coding RNAs, those with over 200 nucleotides in length [1,2,3], are considered a new class of non-protein-coding transcripts

  • A known long-non-coding RNAs (lncRNAs)–disease association is used as a test sample, whereas all the remaining associations are taken as training cases for model learning

  • TPR corresponds to the ratio of the successfully predicted lncRNA–disease associations to the total experimentally verified lncRNA–disease associations, and FPR refers to the percentage of candidate lncRNAs ranked below the threshold

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Summary

Introduction

Long non-coding RNAs (lncRNAs), those with over 200 nucleotides in length [1,2,3], are considered a new class of non-protein-coding transcripts. The mutations and dysregulations of lncRNAs have been proven to be closely related to various human complex diseases [9,10,11], including AIDS [12], diabetes [13], Alzheimer’s Disease (AD) [14], and many types of cancers such as breast [15], prostate [16], hepatocellular [17], and bladder cancer [18]. Genes 2018, 9, 345 the expression of the lncRNA called HOTAIR was shown to be higher in primary breast tumors and metastases, and the HOTAIR expression level was proven to be a powerful predictor of eventual metastasis and death [19,20]. Recent studies have shown that the human H19 gene is frequently overexpressed in the myometrium and stroma during pathological endometrial proliferative events [22]

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