Pearson-CAGI-2013-public

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Overview of how we at Ingenuity interpreted the exomes of a family in which only some person/people -- we had to guess whom -- store too little high-density lipoprotein. Organized by CAGI (genomeinterpretation.org) as one of their yearly challenges, the low-HDL study drew 39 entrants; we were pleased to score best, and to thus be invited to explain how we interpreted the data, and what we found.

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Pearson-CAGI-2013-public

  1. 1.        Genomic  21…              Spo3ng  a  proband  with  Ingenuity  Variant  Analysis   Nathan  Pearson     Principal  Genome  Scien0st   Ingenuity  Systems/QIAGEN     npearson@ingenuity.com     Tweet  @genomenathan,  @ing_sys   Created for CAGI 2013 Pearsongenomeinterpretation.org
  2. 2. 2 Danke  schön!   Proprietary and Confidential •  Sequencees   •  Data  providers  &  assessors   •  CAGI  organizers   •  Sohela  Shah,  Dan  Richards,  Doug  BasseO   Created for CAGI 2013 Pearsongenomeinterpretation.org
  3. 3. 3 How  we  did   Proprietary and Confidential 0 10 20 30 40 50 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 predicted  P(has  low  HDL)   HDL   (hidden)   Created for CAGI 2013 Pearsongenomeinterpretation.org
  4. 4. 4 How  we  did  it   Proprietary and Confidential •  Use  Ingenuity  Variant  Analysis   •  Compare  low-­‐HDL  quartet  (cases)  to  Crohn  exomes  (controls)   •  Find  rare,  func0onally  suspect  variants  in  quartet   •  Among  those,  count  singletons/person   •  Invoke  prior     P(          |          ,  1  sick,  $  >>  0)  ~  1 Created for CAGI 2013 Pearsongenomeinterpretation.org
  5. 5. 5 •  Secure  web  pla_orm  for  interpre'ng  called  human  genomes   •  Smart  interface  to  flexibly  annotate  &  compare  genomes,  in  order  to  shortlist     candidate  variants,  genes,  &  gene  sets   •  Leverages  func;onal  knowledge  base,  with  rigorous  cura0on  of  published   findings,  well  structured  ontology,  smart  interac0on  modeling   •  Sta;s;cally  robust  methods  for  interpre0ng  (mul0-­‐)proband,  matched  tumor,   (mul0-­‐)kindred,  &  big  case/control  cohort  studies   •  Lets  users  readily  share  samples  (pool  cases,  trade  controls)  &  analyses   Proprietary and Confidential Ingenuity®  Variant  Analysis™  in  a  nutshell     Created for CAGI 2013 Pearsongenomeinterpretation.org
  6. 6. 6Proprietary and Confidential Live  walkthrough  with  case/control  exome  data   Created for CAGI 2013 Pearsongenomeinterpretation.org
  7. 7. 7 •  Top  candidate  variant  [censored]?   •  N  low,  methods  young…so  need  skill  (Variant  Analysis),  priors  (behavior),  luck   •  Func0onal  annota0on,  sensible  filtering,  &  extra  controls  help   •  All  here  welcome  to  try  out  Variant  Analysis  –  see  me.   •  Ques0ons?   Proprietary and Confidential Take-­‐home     Created for CAGI 2013 Pearsongenomeinterpretation.org

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