Detection of lncRNA-mRNA interaction modules by integrating eQTL with weighted gene co-expression network analysis

• Published in: Functional & integrative genomics Vol. 19; no. 2; pp. 217 - 225
• Main Authors: Mo, Xing-Bo, Wu, Long-Fei, Lu, Xin, Zhu, Xiao-Wei, Xia, Wei, Wang, Lan, He, Pei, Bing, Peng-Fei, Zhang, Yong-Hong, Deng, Fei-Yan, Lei, Shu-Feng
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.03.2019; Springer Nature B.V
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Animal Genetics and Genomics; Biochemistry; Bioinformatics; Biomedical and Life Sciences; Cell Biology; Data processing; Gene expression; Genomes; Leukocytes (mononuclear); Life Sciences; Microbial Genetics and Genomics; mRNA; NF-κB protein; Original Article; Peripheral blood mononuclear cells; Plant Genetics and Genomics; Signal transduction; Toll-like receptors; HOTAIR; Functional annotation; eQTL; Long noncoding RNA; Weighted gene co-expression network analysis
• ISSN: 1438-793X; 1438-7948
• DOI: 10.1007/s10142-018-0638-4

One major function of lncRNA is to regulate the expression of mRNA, but the patterns of their interactions were largely unknown. We attempted to construct lncRNA-mRNA interaction modules at a genome-wide scale. We performed a genome-wide lncRNA-mRNA eQTL analysis in peripheral blood mononuclear cells of 43 individuals, followed by weighted gene co-expression network analysis and functional enrichment analysis which sought to detect functional modules. There were 4627 significant cis lnc-eQTL pairs ( P  < 1.4 × 10 −6 ) and 1,587,128 significant trans lnc-eQTL pairs ( P  < 3.46 × 10 −9 ). We detected 11 eQTL modules for the lnc-eQTL networks. Among them, five modules showed significant enrichments in GO terms, and three modules showed significant enrichments in specific KEGG pathways (e.g., Toll-like receptor, PI3K-Akt, NF-kappa B, and TNF signaling pathways). lncRNA-protein interaction analysis showed that some well-known functional lncRNAs (HOTAIR, CCDC26, RHPN1-AS1, WT1-AS, and TCL6) in the eQTL module interacted with genes in focal adhesion and PI3K-Akt signaling pathway. We identified biologically functional lncRNA-mRNA interaction modules by integrating eQTL and weighted gene co-expression network analysis. Integrative analysis of lncRNA and mRNA data by applying eQTL analysis and weighted gene co-expression network analysis methods could be helpful for functional annotation of lncRNAs.