Genome-Wide Interactions of Mouse-Plasmodium yoelii Parasite and Identification of Regulators of Type I Interferon Response

• Published in: Cell reports (Cambridge) 2015-07, Vol.12 (4), p.661-672
• Main Authors: Wu, Jian, Cai, Baowei, Sun, Wenxiang, Huang, Ruili, Liu, Xueqiao, Lin, Meng, Pattaradilokrat, Sittiporn, Martin, Scott, Qi, Yanwei, Nair, Sethu C., Bolland, Silvia, Cohen, Jeffrey I., Austin, Christopher P., Long, Carole A., Myers, Timothy G., Wang, Rong-fu, Su, Xin-zhuan
• Format: Article
• Language: English
• ISSN: 2211-1247
• DOI: 10.1016/j.celrep.2015.06.058

Invading pathogens trigger specific host responses, an understanding of which might identify genes that function in pathogen recognition and elimination. In this study, we performed trans-species expression quantitative trait locus (ts-eQTL) analysis using genotypes of the Plasmodium yoelii malaria parasite and phenotypes of mouse gene expression. We significantly linked 1,054 host genes to parasite genetic loci (LOD score ≥ 3.0). Using LOD score patterns, which produced results that differed from direct expression level clustering, we grouped host genes that function in related pathways, allowing functional prediction of unknown genes. As a proof of principle, 14 of 15 randomly selected genes predicted to function in type I interferon (IFN-I) responses were experimentally validated using overexpression, shRNA knockdown, viral infection, and/or infection of KO mice. This study demonstrates an effective strategy for studying gene function, establishes a functional gene database, and identifies regulators in IFN-I pathways.