TY - JOUR
T1 - Genome-wide analysis of host-plasmodium yoelii interactions reveals regulators of the type i interferon response
AU - Wu, Jian
AU - Cai, Baowei
AU - Sun, Wenxiang
AU - Huang, Ruili
AU - Liu, Xueqiao
AU - Lin, Meng
AU - Pattaradilokrat, Sittiporn
AU - Martin, Scott
AU - Qi, Yanwei
AU - Nair, Sethu C.
AU - Bolland, Silvia
AU - Cohen, Jeffrey I.
AU - Austin, Christopher P.
AU - Long, Carole A.
AU - Myers, Timothy G.
AU - Wang, Rong Fu
AU - Su, Xin zhuan
N1 - Funding Information:
This work was supported by the Division of Intramural Research at the National Institute of Allergy and Infectious Diseases (NIAID) and the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH), by Project 111 of the State Bureau of Foreign Experts and Ministry of Education of China (B06016), and supported in part by grants from the National Cancer Institute, NIH (R01CA090327 and R01CA101795) to R.-F.W. B.C. and M.L. were supported in part by the Chinese Scholar Council. We thank Dr. J.S. Verbeek for the Fcgr1 KO mice and Cindy Clark of the NIH Library for editing.
Publisher Copyright:
© 2015 The Authors.
PY - 2015
Y1 - 2015
N2 - 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 R 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, small hairpin RNA knockdown, viral infection, and/or infection of knockout mice. This study demonstrates an effective strategy for studying gene function, establishes a functional gene database, and identifies regulators in IFN-I pathways.
AB - 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 R 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, small hairpin RNA knockdown, viral infection, and/or infection of knockout mice. This study demonstrates an effective strategy for studying gene function, establishes a functional gene database, and identifies regulators in IFN-I pathways.
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U2 - 10.1016/j.celrep.2015.06.058
DO - 10.1016/j.celrep.2015.06.058
M3 - Article
C2 - 26190101
AN - SCOPUS:84947040852
SN - 2211-1247
VL - 12
SP - 661
EP - 672
JO - Cell Reports
JF - Cell Reports
IS - 4
ER -