title: Genome-wide Analysis of Host-Plasmodium yoelii Interactions Reveals Regulators of the Type I Interferon Response.
abstract: 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, 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.
authors.affiliation: Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-8132, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, PRC; Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX 77030, USA.
authors.forename: Baowei
authors.initials: B
authors.lastname: Cai
authors.affiliation: Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-8132, USA.
authors.forename: Wenxiang
authors.initials: W
authors.lastname: Sun
authors.affiliation: National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892-8132, USA.
authors.forename: Ruili
authors.initials: R
authors.lastname: Huang
authors.affiliation: Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-8132, USA.
authors.forename: Xueqiao
authors.initials: X
authors.lastname: Liu
authors.affiliation: Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX 77030, USA.
authors.forename: Meng
authors.initials: M
authors.lastname: Lin
authors.affiliation: Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-8132, USA; Department of Biology, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand.
authors.forename: Sittiporn
authors.initials: S
authors.lastname: Pattaradilokrat
authors.affiliation: National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892-8132, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Martin
authors.affiliation: Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-8132, USA; State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, PRC.
authors.forename: Yanwei
authors.initials: Y
authors.lastname: Qi
authors.affiliation: Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-8132, USA.
authors.forename: Sethu C
authors.initials: SC
authors.lastname: Nair
authors.affiliation: Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-8132, USA.
authors.forename: Silvia
authors.initials: S
authors.lastname: Bolland
authors.affiliation: Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-8132, USA.
authors.forename: Jeffrey I
authors.initials: JI
authors.lastname: Cohen
authors.affiliation: National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892-8132, USA.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Austin
authors.affiliation: Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-8132, USA.
authors.forename: Carole A
authors.initials: CA
authors.lastname: Long
authors.affiliation: Genomic Technologies Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-8132, USA.
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Myers
authors.affiliation: Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX 77030, USA. Electronic address: rwang3@houstonmethodist.org.
authors.forename: Rong-Fu
authors.initials: RF
authors.lastname: Wang
authors.affiliation: Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-8132, USA; State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, PRC. Electronic address: xsu@niaid.nih.gov.
authors.forename: Xin-Zhuan
authors.initials: XZ
authors.lastname: Su
mesh_terms: D000818:Animals; D018503:Genome, Protozoan; D055106:Genome-Wide Association Study; D006790:Host-Parasite Interactions / Q000235:genetics*; D007370:Interferon Type I / Q000235:genetics / Q000378:metabolism*; D008288:Malaria / Q000235:genetics* / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D010967:Plasmodium yoelii / Q000235:genetics* / Q000472:pathogenicity; D040641:Quantitative Trait Loci
chemical_list: D007370:Interferon Type I