title: Prioritizing genes responsible for host resistance to influenza using network approaches.
abstract: BACKGROUND
  The genetic make-up of humans and other mammals (such as mice) affects their resistance to influenza virus infection. Considering the complexity and moral issues associated with experiments on human subjects, we have only acquired partial knowledge regarding the underlying molecular mechanisms. Although influenza resistance in inbred mice has been mapped to several quantitative trait loci (QTLs), which have greatly narrowed down the search for host resistance genes, only few underlying genes have been identified.
  
  
  RESULTS
  To prioritize a list of promising candidates for future functional investigation, we applied network-based approaches to leverage the information of known resistance genes and the expression profiles contrasting susceptible and resistant mouse strains. The significance of top-ranked genes was supported by different lines of evidence from independent genetic associations, QTL studies, RNA interference (RNAi) screenings, and gene expression analysis. Further data mining on the prioritized genes revealed the functions of two pathways mediated by tumor necrosis factor (TNF): apoptosis and TNF receptor-2 signaling pathways. We suggested that the delicate balance between TNF's pro-survival and apoptotic effects may affect hosts' conditions after influenza virus infection.
  
  
  CONCLUSIONS
  This study considerably cuts down the list of candidate genes responsible for host resistance to influenza and proposed novel pathways and mechanisms. Our study also demonstrated the efficacy of network-based methods in prioritizing genes for complex traits.
authors.forename: Suying
authors.initials: S
authors.lastname: Bao
authors.forename: Xueya
authors.initials: X
authors.lastname: Zhou
authors.forename: Liangcai
authors.initials: L
authors.lastname: Zhang
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.forename: Kelvin Kai-Wang
authors.initials: KK
authors.lastname: To
authors.forename: Binbin
authors.initials: B
authors.lastname: Wang
authors.forename: Liqiu
authors.initials: L
authors.lastname: Wang
authors.forename: Xuegong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry, The University of Hong Kong, Hong Kong, China. songy@hku.hk.
authors.forename: You-Qiang
authors.initials: YQ
authors.lastname: Song
mesh_terms: D000818:Animals; D060467:Disease Resistance / Q000235:genetics*; D054884:Host-Pathogen Interactions / Q000235:genetics*; D006801:Humans; D007251:Influenza, Human / Q000235:genetics* / Q000473:pathology / Q000821:virology; D051379:Mice; D009975:Orthomyxoviridae / Q000235:genetics* / Q000472:pathogenicity; D040641:Quantitative Trait Loci / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D014409:Tumor Necrosis Factor-alpha