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

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Abstract

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.

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Acknowledgments

The study was supported by the Natural Science Foundation of China (31401079, 81473046, 81373010, 81502868, 81401343, 81541068), the Natural Science Research Project of Jiangsu Provincial Higher Education (16KJA330001), the Natural Science Foundation of Jiangsu Province (BK20130300, BK20150346), the Project funded by China post-doctoral Science Foundation (2014M551649), the Startup Fund from Soochow University (Q413900313, Q413900112, Q413900712), and a Project of the Priority Academic Program Development of Jiangsu Higher Education Institutions.

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Correspondence to Shu-Feng Lei.

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This study was approved by the ethical committee of Soochow University. All the 43 participants are Chinese Han and were signed an informed consent document before recruitment.

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The authors declare that they have no conflict of interest.

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Mo, XB., Wu, LF., Lu, X. et al. Detection of lncRNA-mRNA interaction modules by integrating eQTL with weighted gene co-expression network analysis. Funct Integr Genomics 19, 217–225 (2019). https://doi.org/10.1007/s10142-018-0638-4

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  • DOI: https://doi.org/10.1007/s10142-018-0638-4

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