Abstract

BackgroundIt has been widely accepted that long non-coding RNAs (lncRNAs) play important roles in the development and progression of human diseases. Many association prediction models have been proposed for predicting lncRNA functions and identifying potential lncRNA-disease associations. Nevertheless, among them, little effort has been attempted to measure lncRNA functional similarity, which is an essential part of association prediction models.ResultsIn this study, we presented an lncRNA functional similarity calculation model, IDSSIM for short, based on an improved disease semantic similarity method, highlight of which is the introduction of information content contribution factor into the semantic value calculation to take into account both the hierarchical structures of disease directed acyclic graphs and the disease specificities. IDSSIM and three state-of-the-art models, i.e., LNCSIM1, LNCSIM2, and ILNCSIM, were evaluated by applying their disease semantic similarity matrices and the lncRNA functional similarity matrices, as well as corresponding matrices of human lncRNA-disease associations coming from either lncRNADisease database or MNDR database, into an association prediction method WKNKN for lncRNA-disease association prediction. In addition, case studies of breast cancer and adenocarcinoma were also performed to validate the effectiveness of IDSSIM.ConclusionsResults demonstrated that in terms of ROC curves and AUC values, IDSSIM is superior to compared models, and can improve accuracy of disease semantic similarity effectively, leading to increase the association prediction ability of the IDSSIM-WKNKN model; in terms of case studies, most of potential disease-associated lncRNAs predicted by IDSSIM can be confirmed by databases and literatures, implying that IDSSIM can serve as a promising tool for predicting lncRNA functions, identifying potential lncRNA-disease associations, and pre-screening candidate lncRNAs to perform biological experiments. The IDSSIM code, all experimental data and prediction results are available online at https://github.com/CDMB-lab/IDSSIM.

Highlights

  • It has been widely accepted that long non-coding RNAs play important roles in the development and progression of human diseases

  • Results demonstrated that IDSSIM is superior to compared models, and can improve accuracy of disease semantic similarity effectively, leading to increase the association prediction ability of our model

  • Results showed that most of potential disease-associated long non-coding RNAs (lncRNAs) predicted by IDSSIM can be confirmed by databases and literatures, implying that IDSSIM can serve as a promising tool for predicting lncRNA functions, identifying potential lncRNA-disease associations, and pre-screening candidate lncRNAs to perform biological experiments

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Summary

Introduction

It has been widely accepted that long non-coding RNAs (lncRNAs) play important roles in the development and progression of human diseases. Inferring lncRNA functions, as well as detecting lncRNA-disease associations, can help us to deeply understand the pathogenesis of human diseases [9, 10]. The functional similarity calculation model is a valuable supplement to characterize lncRNA functions with less time and costs, which can be further studied by lncRNAdisease association detection methods to better understand underlying genetic mechanisms of human diseases at lncRNA level, leading to more accurate associations between lncRNAs and diseases being captured [11,12,13]

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