Predicting the functions of long noncoding RNAs using RNA-seq based on Bayesian network.

Yun Xiao,Xia Li,Yonghui Gong,Jinyuan Xu,Jing Bai,Yanling Lv,Jing Hu,Hongying Zhao,Feng Li,Fulong Yu

doi:10.1155/2015/839590

Abstract

Long noncoding RNAs (lncRNAs) have been shown to play key roles in various biological processes. However, functions of most lncRNAs are poorly characterized. Here, we represent a framework to predict functions of lncRNAs through construction of a regulatory network between lncRNAs and protein-coding genes. Using RNA-seq data, the transcript profiles of lncRNAs and protein-coding genes are constructed. Using the Bayesian network method, a regulatory network, which implies dependency relations between lncRNAs and protein-coding genes, was built. In combining protein interaction network, highly connected coding genes linked by a given lncRNA were subsequently used to predict functions of the lncRNA through functional enrichment. Application of our method to prostate RNA-seq data showed that 762 lncRNAs in the constructed regulatory network were assigned functions. We found that lncRNAs are involved in diverse biological processes, such as tissue development or embryo development (e.g., nervous system development and mesoderm development). By comparison with functions inferred using the neighboring gene-based method and functions determined using lncRNA knockdown experiments, our method can provide comparable predicted functions of lncRNAs. Overall, our method can be applied to emerging RNA-seq data, which will help researchers identify complex relations between lncRNAs and coding genes and reveal important functions of lncRNAs.

Highlights

There are only ∼1% of human transcripts encoding proteins [1], and a large fraction of transcripts is long noncoding RNAs, which are an unknown component of mammalian genomes [2]
We found that PlncRNA-1 can affect POFUT1 gene involved in Notch signaling pathway, which is required for normal prostatic epithelial cell proliferation and differentiation [55]
We performed GO enrichment analysis based on the affected genes for the determination of its functions. Among these 48 long noncoding RNAs (lncRNAs), we found that 38 lncRNAs show overlapping of functions identified between our approach and knockdown-based experiments; 4 were not involved in any functions based on knockdown expression data, and 5 were not based on our approach

Summary

Introduction

There are only ∼1% of human transcripts encoding proteins [1], and a large fraction of transcripts is long noncoding RNAs (lncRNAs), which are an unknown component of mammalian genomes [2]. LncRNAs are spliced, polyadenylated ranging from 200 bp to more than 10 kb [3,4,5]. They are transcribed from genome regions that are known to lack protein-coding genes, open reading frames, and other properties necessary to be translated into proteins [6, 7]. The functions of most lncRNAs are largely unknown in comparison to small noncoding RNAs (i.e., microRNAs) [18]. Predicting functions of lncRNAs remains a greatly substantial challenge

Methods

Findings

Discussion

Conclusion