Abstract

BackgroundLong non-coding RNAs (lncRNAs) are related to human diseases by regulating gene expression. Identifying lncRNA-disease associations (LDAs) will contribute to diagnose, treatment, and prognosis of diseases. However, the identification of LDAs by the biological experiments is time-consuming, costly and inefficient. Therefore, the development of efficient and high-accuracy computational methods for predicting LDAs is of great significance.ResultsIn this paper, we propose a novel computational method (gGATLDA) to predict LDAs based on graph-level graph attention network. Firstly, we extract the enclosing subgraphs of each lncRNA-disease pair. Secondly, we construct the feature vectors by integrating lncRNA similarity and disease similarity as node attributes in subgraphs. Finally, we train a graph neural network (GNN) model by feeding the subgraphs and feature vectors to it, and use the trained GNN model to predict lncRNA-disease potential association scores. The experimental results show that our method can achieve higher area under the receiver operation characteristic curve (AUC), area under the precision recall curve (AUPR), accuracy and F1-Score than the state-of-the-art methods in five fold cross-validation. Case studies show that our method can effectively identify lncRNAs associated with breast cancer, gastric cancer, prostate cancer, and renal cancer.ConclusionThe experimental results indicate that our method is a useful approach for predicting potential LDAs.

Highlights

  • Long non-coding RNAs is a kind of non-protein-coding RNA, which has over 200 nucleotides [1]

  • To overcome the time-consuming and expensive shortcomings of experimental methods, researchers have focused on identifying Long non-coding RNAs (lncRNAs)-disease potential association by computational methods

  • We propose an effective lncRNA-disease associations (LDAs) prediction method using graph-level graph attention network called gGATLDA

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Summary

Introduction

Long non-coding RNAs (lncRNAs) is a kind of non-protein-coding RNA, which has over 200 nucleotides [1]. More and more researches have indicated that the mutations and dysregulations of lncRNAs are closely related to the development and progression of various human complex diseases, including cancer [2]. Wang and Zhong B MC Bioinformatics (2022) 23:11 cancer (NSCLC), and its downregulated expression could suppress NSCLC cell proliferation and cell cycle progression by inhibiting the Wnt/βcatenin pathway [4]. LncRNA-IUR family was a key negative regulator of Bcr-Abl- induced tumorigenesis. LncRNA-IUR-5 suppressed Bcr-Abl-mediated tumorigenesis by negatively regulating STAT5-mediated expression of CD71 [6]. The identification of disease-related lncRNAs will help to understand human complex disease mechanism, disease diagnosis, treatment, prognosis and prevention at lncRNA level. Long non-coding RNAs (lncRNAs) are related to human diseases by regulating gene expression. The development of efficient and high-accuracy computational methods for predicting LDAs is of great significance

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