Journal
CELL REPORTS
Volume 12, Issue 4, Pages 661-672Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2015.06.058
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Funding
- Division of Intramural Research at the National Institute of Allergy and Infectious Diseases (NIAID)
- National Center for Advancing Translational Sciences (NCATS)
- National Institutes of Health (NIH)
- Project 111 of the State Bureau of Foreign Experts and Ministry of Education of China [B06016]
- National Cancer Institute, NIH [R01CA090327, R01CA101795]
- Chinese Scholar Council
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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.
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