the empowered genome community (ashg 2013)

Talk 102 Empowered Genome Community [email protected] data at ow.ly/pYNSC

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THE EMPOWERED��GENOME COMMUNITY��

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SHAREABLE JOINT INTERPRETATION OF ��HUMAN WHOLE GENOMES FOR RESEARCH ��

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NATHAN PEARSON, PRINCIPAL GENOME SCIENTIST, QIAGEN

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PGP UYG

Rise of the Genonauts

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EQUENCEES

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source: xkcd.com/893

moonwalkers

~300 aware whole-genome sequencees


PGP UYG

Rise of the Genonauts


One genome: Much ado about…something? Today, a typical healthy sequencee gets back

One genome: Much ado about…something?


Today, a typical healthy sequencee gets back

•  Vast raw(ish) data in tricky formats •  A prognostic-minded single-genome report (frozen waffles) •  An app(?) for browsing fenced-in parts of one genome and, if intrepid, may learn •  A fair bit about ancestry •  Less about drugs and mirrors •  A smidgen about family health •  What’s missing (meta-lesson)

Making a genome reliably informative


Why one genome says so little (yet)

•  Health is complex •  Rare variants abound •  Data are scarce 3 challenges loom

•  Sequencees can’t easily mine much from their genomes. •  Deep insight entails first comparing many well-phenotyped genomes. •  Researchers need more such genomes.



3 challenges loom


Why one genome says so little (yet)

•  Health is complex •  Rare variants abound •  Data are scarce



3 challenges loom



•  Give sequencees access to a secure platform for exploring genomes, singly and jointly, with other citizen-scientists & full-time researchers. •  Help healthy adults make their genomes directly useful, to ask ��

What can my our genomes do for me humanity?��

•  Leverage deep functional knowledge & sensible comparison methods ��(e.g., rare variant association tests) to give current data silos (PGP/hard drives) a working bakery for collaborative insight, via Ingenuity Variant Analysis.��

•  Let sequencees own and control their private data.

The Empowered Genome Community ��ow.ly/pZCXB


•  Secure web platform for interpreting called human genomes

•  Simple interface to flexibly annotate & compare genomes, to shortlist candidate variants, genes, & gene sets

•  Leverages deep functional knowledge base, with rigorously curated published findings, well structured ontology, & smart interaction modeling

•  Statistically robust methods for interpreting (multi-)proband/kindred, matched tumor, and big case/control cohort studies

•  Shareable, to spark collaborative discovery

•  Hear Tracy Brandt (Mt. Sinai) & Phil Tsao (Stanford) present work using Variant Analysis today at 12:30 in room 051

Ingenuity Variant Analysis in a nutshell


•  Pool well-phenotyped genomes to unravel common, complex disease, highlighting utility of community model

•  111 phenotype-surveyed PGP genomes (66 cases, 55 controls) •  Openly crowd-refinable, with an eye to publishing robust findings •  First-pass findings highlight 12 plausibly myopia-relevant genes

enriched with rare, functionally suspect variants in cases v. controls

•  Refine findings with your insights on myopia etiology & epidemiology, sample structure, validation.

Proof of principle: Open, collaborative myopia analysis��variants.ingenuity.com/community-myopia


Using Variant Analysis


Using Variant Analysis: Call confidence & credibility


Using Variant Analysis: General functional intrigue


Using Variant Analysis: Rarity


Using Variant Analysis: Rare variant association


Using Variant Analysis: Myopia-relevance


Using Variant Analysis: Saving your filters


Bring your genome, to interpret it – and, if desired, pool with others.

•  If a PGP sequencee, request your genome. •  If a UYG/other sequencee, upload your genome as .vcf. •  Explore it, and share with others if you wish.

Bring your mind, to help interpret Community genomes. •  Refine the myopia analysis, export your filter settings, and write me! •  Collaborate on other forthcoming studies.

Bring your wishlist, to find needed cases/controls. •  Write me, to coordinate outreach.

Joining the Empowered Genome Community ��ow.ly/q56u4

Thanks. PGP and UYG sequencees Jason Bobe, Michael Chou, George Church, Madeleine Price-Ball John Mayfield, CarriLyn Mead, Erica Ramos Kevin Davies, Yaniv Erlich, Robert Green, Razib Khan, Gholson Lyon, Chris Mason, David Mittelman, Ayanna Monteverdi, Elin Silveous, Dale Yuzuki David Bachinsky, Steven Berley, Massimo Delledonne, David Delorenzo, Joel Dudley, William Faucett, Patrick Frosk, Terry Gaasterland, Konrad Karczewski, Joanne Mason, Steve Pinker, Jeannie Schaller, Randeep Singh, Elia Stupka, Eric Topol, Elizabeth Varga, Ron Zimmern Brent Applegate, Dione Bailey, Doug Bassett, Sarah Betadam, Carla Bullitt, Helen Cao, David Dailey, Julie Deschenes, Aysel Heckel, Andreas Krämer, Laurent Martin, Antonio Montano, Bryant Macy, Anand Muthiah, Jake Leschly, Curt Palm, Dan Richards, Colin Sanford, Thomas Theuringer


the empowered genome community (ashg 2013)

Health & Medicine