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SUMMARY:Detecting important mutations and epistatic interactions in H5N1 a
 nd H1N1 Influenza viruses using Bayesian Graphical Models. - Sam Lycett (U
 niversity of Edinburgh)
DTSTART:20100211T163000Z
DTEND:20100211T173000Z
UID:TALK22556@talks.cam.ac.uk
CONTACT:Olivier Restif
DESCRIPTION:Influenza viruses contain 8 RNA segments coding for 10-11 prot
 eins\, including the two surface proteins Hemagluttinin (HA) and Neuramini
 dase (NA) which determine the viral subtype.  In addition to mutations in 
 the surface proteins (e.g. to enable binding to a mammalian receptor)\, mu
 tations in the segments coding for internal proteins are also important in
  virulence and adapting the virus from avian to mammalian hosts.\n\nIn thi
 s talk I will describe how Bayesian Graphical Models (BGMs) can be used to
  detect site-site and site-phenotype associations in Influenza A viruses. 
  BGMs represent the direct conditional dependencies between variables (mut
 ations at amino acid sites or virulence phenotype)\, rather than just corr
 elations\, as edges in a network.  Here BGMs were inferred using a Monte C
 arlo Markov Chain technique to sample from appropriate network structures\
 , and cross validation\, permutation tests and parametric bootstrapping wa
 s used to improve model robustness.\n\nFirstly\, I will describe the detec
 tion of the set of mutations directly associated with virulence in mammals
  in highly pathogenic avian influenza H5N1 (HPAI H5N1 is highly pathogenic
  in chickens\, but not necessarily in mammals).  Secondly an investigation
  into adaptations of influenza viruses from avian to mammalian hosts accou
 nting for the role of founder effects\, shared ancestry and epistatic inte
 ractions will be described.  Here the variables are host change (avian fro
 m/to human or swine) and mutational histories of the amino acid sites (inf
 erred using a phylogenetic tree and codon model).  As well as changes in t
 he Hemagglutinin receptor binding site for H1N1 and H5N1 subtypes\, there 
 were several sites directly associated with host change in the polymerases
  and NS1.  Networks of interactions between HA antigenic sites and the rec
 eptor binding site\, and within the polymerase complex were also identifie
 d.
LOCATION:Meeting room 12\, Centre for Mathematical Sciences
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