A network based method for analysis of lncRNA-disease associations and prediction of lncRNAs implicated in diseases

PLoS One. 2014 Jan 31;9(1):e87797. doi: 10.1371/journal.pone.0087797. eCollection 2014.

Authors

Xiaofei Yang¹, Lin Gao¹, Xingli Guo¹, Xinghua Shi², Hao Wu¹, Fei Song¹, Bingbo Wang¹

Affiliations

¹ School of Computer Science and Technology, Xidian University, Xi'an, Shaanxi, China.
² Department of Bioinformatics and Genomics, College of Computing and Informatics, University of North Carolina at Charlotte, Charlotte, North Carolina, Unites States of America.

Abstract

Increasing evidence has indicated that long non-coding RNAs (lncRNAs) are implicated in and associated with many complex human diseases. Despite of the accumulation of lncRNA-disease associations, only a few studies had studied the roles of these associations in pathogenesis. In this paper, we investigated lncRNA-disease associations from a network view to understand the contribution of these lncRNAs to complex diseases. Specifically, we studied both the properties of the diseases in which the lncRNAs were implicated, and that of the lncRNAs associated with complex diseases. Regarding the fact that protein coding genes and lncRNAs are involved in human diseases, we constructed a coding-non-coding gene-disease bipartite network based on known associations between diseases and disease-causing genes. We then applied a propagation algorithm to uncover the hidden lncRNA-disease associations in this network. The algorithm was evaluated by leave-one-out cross validation on 103 diseases in which at least two genes were known to be involved, and achieved an AUC of 0.7881. Our algorithm successfully predicted 768 potential lncRNA-disease associations between 66 lncRNAs and 193 diseases. Furthermore, our results for Alzheimer's disease, pancreatic cancer, and gastric cancer were verified by other independent studies.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Algorithms*
Alzheimer Disease / genetics*
Alzheimer Disease / metabolism
Gene Regulatory Networks*
Humans
Pancreatic Neoplasms / genetics*
Pancreatic Neoplasms / metabolism
RNA, Long Noncoding / genetics*
RNA, Long Noncoding / metabolism
RNA, Neoplasm / genetics*
RNA, Neoplasm / metabolism
Sequence Analysis, RNA
Stomach Neoplasms / genetics*
Stomach Neoplasms / metabolism

Substances

RNA, Long Noncoding
RNA, Neoplasm

Grants and funding

This work was supported by the National Natural Science Foundation of China (Grant No. 60933009, 61070137, 91130006, 61303118, & 61303122), the website is http://www.nsfc.gov.cn/publish/portal1/; the Fundamental Research Funds for the Central Universities (XIDIAN UNIVERSITY, No. K50512230005 & K50512230003). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.