Summary  Part  4  

•  Loca-on  =>  Look  out  for  Feature  •  Object  crea-on  from  Adaptor  or  from  API  object  •  No  allele  strings  for  structural  varia-ons,  only  coordinates  •  Varia-onFeature  already  contains  a  lot  of  useful  informa-on  to  

study  consequences  BUT:  •  Go  further  down  to  TranscriptVaria-on  

•  Loca-on  specific  informa-on  of  Variant  overlapping  a  Transcript  

•  And  TranscriptVaria-onAllele  •  Allele  specifc  informa-on  on  Transcript  

•  PhenotypeFeatures  can  be  obtained  from  Varia-on  and  StructuralVaria-on  objects  

Linkage disequilibrium •  Linkage  disequilibrium  (LD)  is  a  measure  of  how  frequently  

alleles  at  two  separate  loci  are  inherited  together  on  the  same  haplotype  

•  Two  common  measures    •  r2,  D’    (r2  =  1  à  perfect  LD)  

High  LD  

Popula-on  A  

Individual  A1  

Individual  A2  

Individual  A3  

Individual  A4  

Individual  A5  

Individual  A6  

Popula-on  B  

Individual  B1  

Individual  B2  

Individual  B3  

Individual  B4  

Individual  B5  

Individual  B6  

Locus  1   Locus  2   Locus  3   Locus  4  

Lower  LD  

T  G  

Linkage  disequilibrium  container  objects  

•  LDFeatureContainer  (LDFeatureContainerAdaptor)  •  Contains pairwise LD values in a region •  Can contain values for multiple populations •  Values are calculated on the fly •  Most  methods  return  hash  references:  

my  $ldf_container  =  $ldfca-­‐>fetch_by_Slice($slice);  #  returns  listref  of  hashrefs  my  $ld_values  =  $ldf_container-­‐>get_all_ld_values();  foreach  my  $ld_hash_ref  (@$ld_values)  {          my  $r2  =  $ld_hash_ref-­‐>{r2};  #  look  up  type          my  $variation_1  =  $ld_hash_ref-­‐>{variation1};  

 …  }  

Varia-on  sets  •  Arbitrary  collec-ons  of  Varia-ons  (different  from  the  sources)  •  Useful  to  limit  your  script  to  important  subsets  

•  All  Varia-ons  linked  to  entries  in  OMIM  •  Variants  on  Illumina  chips  •  …  

•  Some-mes  contain  millions  of  Varia-ons,  in  which  case  you  can  fetch  an  Iterator  instead  of  a  list  

my  $vs  =  $variation_set_adaptor-­‐>fetch_all_by_name(‘All  phenotype-­‐associated  variants’);    print  $vs-­‐>description();  my  @variations  =  @{$vs-­‐>get_all_Variations()};  my  @sub_sets  =  @{$vs-­‐>get_all_sub_VariationSets()};  

hfp://www.ensembl.org/info/docs/varia-on/data_descrip-on.html#varia-on_sets  

What next

•  Ensembl  tool  to  predict  the  func-onal  consequences  of  variants,  using  the  Ensembl  Varia-on  API  

•  2  ways  to  use  it:  •  Through  the  web  interface  •  Using  the  standalone  perl  script  

•  Query  the  databases  or  a  downloaded  cache  file  •  Several  input  formats:  VEP  tabulated  format,  VCF,  Pileup,  

HGVS  iden-fieres,  Variant  iden-fiers  •  A  lot  of  op-ons  available  (data  filters,  output  formats)  

hfp://www.ensembl.org/info/docs/varia-on/vep/index.html  

Summary  

•  hfp://www.ensembl.org/info/docs/varia-on/index.html  •  Data  •  Database  •  Perl  API    •  VEP  

•  Ensembl  developers  mailing  list  •  dev@ensembl.org  

Ensembl  Acknowledgements  

Ensembl  Team  •  Ensembl  Varia-on  

•  William  McLaren  •  Laurent  Gil  •  Sarah  Hunt    •  Fiona  Cunningham  (head)  

 

•  Paul  Flicek,  Steve  Searle  and  the  en-re  Ensembl  Team  

 

Funding            European  Commission  Framework  Programme  7  

Figures

•  Babies:  hfp://www.impawards.com/2010/posters/babies.jpg  •  Cilantro  hfp://spifoon.23andme.com/wp-­‐content/uploads/2012/09/cilantro-­‐

iStock_000004725589-­‐300x199.jpg  •  Path  1  hfp://www.jeremycwilson.com/wp-­‐content/uploads/2010/05/path.jpg  •  Path  2  hfp://www.photographyblogger.net/wp-­‐content/uploads/

2011/05/83594459_70d9688f23.jpg  •  Path  3  hfp://liveholiness.com/wp-­‐content/uploads/2012/02/path.jpg