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140127 GIAB Intro
140127 GIAB Intro
140127 GIAB Intro
140127 GIAB Intro
140127 GIAB Intro
140127 GIAB Intro
140127 GIAB Intro
140127 GIAB Intro
140127 GIAB Intro
140127 GIAB Intro
140127 GIAB Intro
140127 GIAB Intro
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140127 GIAB Intro

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  • 1. Genome in a Bottle Consortium January 2014 Stanford University Reference Materials for Clinical Applications of Human Genome Sequencing Marc Salit, Ph.D. and Justin Zook, Ph.D National Institute of Standards and Technology Advances in Biological/Medical Measurement Science (ABMS @ Stanford)
  • 2. Advances in Biological/Medical Measurement Science Program • Measurement Science and Standards for Quantitative Biology – enable commercial and clinical adoption of innovations • NIST, Stanford University, Private Affiliates – currently Life Technologies and Agilent – soliciting more participation! • NIST staff engaged in ABMS to be located on Stanford campus and at NIST in Gaithersburg, MD – about 9 scientists at outset • great postdoc opportunities – embedding postdocs in faculty groups – initial portfolio genomics, functional genomics, synthetic biology abms@nist.gov
  • 3. Genome in a Bottle Consortium Development • NIST met with sequencing technology developers to assess standards needs – Stanford, June 2011 • Open, exploratory workshop – ASHG, Montreal, Canada – October 2011 • Small, invitational workshop at NIST to develop consortium for human genome reference materials – FDA, NCBI, NHGRI, NCI, CDC, Wash U, Broad, technology developers, clinical labs, CAP, PGP, Partners, ABRF, others – developed draft work plan – April 2012 • Open, public meeting at NIST to formally establish consortium, present draft work plan – formed working groups – identified candidate genomes – established principles of: • • • • reference material selection characterization informatics performance metrics – August 2012 • Open, public workshop at XGen Congress – March 2013 • Website – www.genomeinabottle.org
  • 4. Well-characterized, stable RMs • Obtain metrics for validation, QC, QA, PT • Determine sources and types of bias/error • Learn to resolve difficult structural variants • Improve reference genome assembly • Optimization – integration of data from multiple platforms – sequencing and analysis • Enable regulated applications Comparison of SNP Calls for NA12878 on 2 platforms, 3 analysis methods
  • 5. Measurement Process – materials will be certified for their variants against a reference sequence, with confidence estimates Sample gDNA isolation generic measurement process • gDNA reference materials will be developed to characterize performance of a part of process Library Prep Sequencing Alignment/Mapping Variant Calling Confidence Estimates Downstream Analysis
  • 6. Putting “Genomes” in Bottles • NIST working with GiaB to select genomes • Current plan CEPH Utah Pedigree 1463 12889 – NA12878 HapMap sample as Pilot sample • 8 trios, focus on children • varying biogeographic ancestry 12891 12877 • part of 17-member pedigree – trios from PGP as more complete set 12890 12892 12878 11 children, Birth Order Redacted 12879 12880 12881 12882 12883 12884 12885 12886 12887 12888 12893
  • 7. Genome in a Bottle Working Groups Reference Material Selection & Design Meaurements for Reference Material Characterization Andrew Grupe, Celera Mike Eberle, Illumina •Develop prioritized list of whole human genomes for Reference Materials •Identify candidate approaches and materials for artificial RMs •Develop prioritized list Bioninformatics, Data Integration, and Data Representation Steve Sherry, NCBI •Develop consensus plan for experimental characterization of Reference Materials •Develop plan for integrating experimental data and forming consensus variant calls and confidence estimates •Develop consensus plan for data representation Performance Metrics & Figures of Merit Deanna Church, Personalis •User interface to the Genome-in-a-Bottle Reference Material •“Dashboard” •what an end user will see and report to understand and describe the performance of their experiment •variant call accuracy •process performance measures to enable optimization
  • 8. Agenda Monday • Breakfast and registration • Welcome and Context Setting • NIST RM Update and Status Report • Charge to Working Groups • Coffee Break • Working Group Breakout Discussions • Lunch (provided) • Informal Working Group Reports • Coffee Break • Breakout Topical Discussions – Topic #1: Moving beyond the 'easy' variants and regions of the genome – Topic #2: Selecting future genomes for Reference Materials Tuesday • Breakfast and registration • Use cases: Experiences using the pilot Reference Material • Discussion of plans to release pilot Reference Material • Coffee Break • Working Group Breakout discussions • Lunch (provided) • Working Group leaders present plans and discussion • Steering committee Overview • First meeting of the Steering Committee (others adjourn)
  • 9. Agenda Tuesday Monday • Breakfast and registration • Breakfast and registration • Use cases: Experiences using the pilot • Welcome and Context Setting Reference Material • NIST RM Update and Status Report • Discussion of plans to release pilot • Charge to Working Groups Reference Material • Coffee Break • Coffee Break • Slides Group be made available on SlideShare after Working will Breakout Discussions • Working Group Breakout discussions • the workshop (see genomeinabottle.org). Lunch (provided) • Lunch (provided) • Informal Working Group Reports • Working Group leaders present plans • Coffee Break and discussion • Tweets are Discussions unless• the speaker requests Breakout Topical welcome Steering committee Overview Please Note – Topic #1: Moving beyond the 'easy' variants and regions of the genome – Topic #2: Selecting future genomes for Reference Materials • otherwise. Please use #giab First meeting of the Steering as the hashtag Committee (others adjourn) .
  • 10. NIST Reference Materials Pilot RM - NA12878 Personal Genome Project • 8300 10ug vials of NA12878 gDNA @ NIST 4/2013 • Ashkenazim trio DNA expected ~Dec 2013 • Asian son DNA expected ~Dec 2013 – Available for sequencing by GIAB participants – target for release as NIST RM 2/2014 • SNPs, small indels • Will be sequenced at ~10 labs – ~4 technologies, multiple modes • Received “Human Subjects Approval” for release of NA12878 as NIST RM – Parents’ cell lines in process at Coriell • “Human subjects review” close to approval for release of PGP genomes as NIST RMs • Plan is 5-6 additional trios of diverse ancestry – Ideally, african, asian, hispanic – What should we do if PGP doesn’t have trios from each of these groups?
  • 11. Consenting Genomes for use as Reference Materials • Risk of re-identification – this is a real risk – privacy – implications for family members • • Meaning of possibility of withdrawal Commercial application – indirect, research – direct, derived products • PGP project currently state-of-art – broad and direct – test to demonstrate understanding • • “Wild West” Coriell MTA for PGP genomes now explicitly permits commercial redistribution/modification/…
  • 12. Steering Committee • Genome in a Bottle Consortium Governance – – – – decision making prioritization guidance development of resources if needed • end-of-day Tuesday • Agenda – composition of the steering committee – rapporteur – Consortium scope • • • • RM portfolio interlab studies cancer consortium imprimatur – adopt, or endorse non-NIST RMs? • Liaison with other organizations • Priorities for future genome RMs • Version strategy for reference data

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