pearson-cagi-2013-public
DESCRIPTION
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.TRANSCRIPT
1 Proprietary and Confiden0al
Genomic 21… Spo3ng a proband with Ingenuity Variant Analysis
Nathan Pearson Principal Genome Scien0st Ingenuity Systems/QIAGEN [email protected] Tweet @genomenathan, @ing_sys
Created for CAGI 2013 Pearson genomeinterpretation.org
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Danke schön!
Proprietary and Confidential
• Sequencees
• Data providers & assessors
• CAGI organizers
• Sohela Shah, Dan Richards, Doug BasseO
Created for CAGI 2013 Pearson genomeinterpretation.org
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How we did
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predicted P(has low HDL)
HDL (hidden)
Created for CAGI 2013 Pearson genomeinterpretation.org
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How we did it
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• 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 Pearson genomeinterpretation.org
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• 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 Pearson genomeinterpretation.org
6 Proprietary and Confidential
Live walkthrough with case/control exome data
Created for CAGI 2013 Pearson genomeinterpretation.org
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• 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 Pearson genomeinterpretation.org