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SUMMARY:Beyond the reference genome:  inference using prior knowledge of 
 the diversity of a species. - Dr Zamin Iqbal\, Wellcome Trust Centre for H
 uman Genetics\, University of Oxford 
DTSTART:20160428T130000Z
DTEND:20160428T140000Z
UID:TALK64872@talks.cam.ac.uk
CONTACT:Caroline Newnham
DESCRIPTION:Encoding the genetic diversity of a species into a ³graph ref
 erence²\, with\napplications to antibiotic-resistance and antigenic varia
 tion\n\nThe choice of reference object used to represent the genome of a s
 pecies\nhas far reaching effects on biological inference. The use of a ³r
 eference\ngenome² made pragmatic sense when sequencing was expensive. How
 ever it can\nalso lead to under-detection of non-reference alleles and var
 ious\nartefacts. The problem is substantial in regions of genomes of high\
 ndiversity\, such as the human MHC\, or where unusual mutational mechanism
 s\noccur\, as observed in the var genes in P. falciparum\, for instance.\n
 Indeed\, the limitations of a single reference genome have long been\nreco
 gnized in bacterial genomics\, where the term pan-genome has been\ncoined 
 to refer to the full set of genes found across all individuals of a\nspeci
 es. Recently progress has been made towards using an ensemble of\ngenomes 
 or variation data as a first-class object . However many\nalgorithmic chal
 lenges remain and few implementations exist. I will\ndiscuss two lines of 
 research from my group\, based on the idea of building\na reference graph 
 of known sequence and variation in a species. The first\nrelates to the pr
 ediction of antibiotic resistance in bacteria\, recently\npublished for S.
  aureus and M. tuberculosis\n(nature.com/ncomms/2015/151221/ncomms10063/fu
 ll/ncomms10063.html). The\nsecond shows how  a new data structure based on
  a generalised\nBurrows-Wheeler Transform and FM-index allow encoding of a
  graph of\nvariation and read-mapping to the graph. I will show the impact
  of this\nmethod on the study of antigenic diversity in P. falciparum\, th
 e parasite\nresponsible for the most deadly form of malaria.
LOCATION:Biffen Lecture Theatre\, Department of Genetics\, Downing Site
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