title: Coordinated evolution among hepatitis C virus genomic sites is coupled to host factors and resistance to interferon.
abstract: Machine-learning methods in the form of Bayesian networks (BN), linear projection (LP) and self-organizing tree (SOT) models were used to explore association among polymorphic sites within the HVR1 and NS5a regions of the HCV genome, host demographic factors (ethnicity, gender and age) and response to the combined interferon (IFN) and ribavirin (RBV) therapy. The BN models predicted therapy outcomes, gender and ethnicity with accuracy of 90%, 90% and 88.9%, respectively. The LP and SOT models strongly confirmed associations of the HVR1 and NS5A structures with response to therapy and demographic host factors identified by BN. The data indicate host specificity of HCV evolution and suggest the application of these models to predict outcomes of IFN/RBV therapy.
authors.affiliation: Molecular Epidemiology & Bioinformatics Laboratory, Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA, USA. jlara@cdc.gov
authors.forename: James
authors.initials: J
authors.lastname: Lara
authors.forename: John E
authors.initials: JE
authors.lastname: Tavis
authors.forename: Maureen J
authors.initials: MJ
authors.lastname: Donlin
authors.forename: William M
authors.initials: WM
authors.lastname: Lee
authors.forename: He-Jun
authors.initials: HJ
authors.lastname: Yuan
authors.forename: Brian L
authors.initials: BL
authors.lastname: Pearlman
authors.forename: Gilberto
authors.initials: G
authors.lastname: Vaughan
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Forbi
authors.forename: Guo-Liang
authors.initials: GL
authors.lastname: Xia
authors.forename: Yury E
authors.initials: YE
authors.lastname: Khudyakov
mesh_terms: D001499:Bayes Theorem; D019143:Evolution, Molecular; D016679:Genome, Viral / Q000235:genetics; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics*; D007372:Interferons / Q000494:pharmacology; D012254:Ribavirin / Q000494:pharmacology
chemical_list: D012254:Ribavirin; D007372:Interferons