- 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 [email protected] 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
applicationsComparison 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
estimatesSamplegDNA isolationgeneric measurement process gDNA
reference materials will be developed to characterize performance
of a part of processLibrary PrepSequencingAlignment/MappingVariant
CallingConfidence EstimatesDownstream Analysis 6. Putting Genomes
in Bottles NIST working with GiaB to select genomes Current
planCEPH Utah Pedigree 1463 12889 NA12878 HapMap sample as Pilot
sample 8 trios, focus on children varying biogeographic
ancestry1289112877 part of 17-member pedigree trios from PGP as
more complete set12890128921287811 children, Birth Order Redacted
1287912880128811288212883128841288512886128871288812893 7. Genome
in a Bottle Working Groups Reference Material Selection &
DesignMeaurements for Reference Material CharacterizationAndrew
Grupe, CeleraMike Eberle, IlluminaDevelop prioritized list of whole
human genomes for Reference Materials Identify candidate approaches
and materials for artificial RMs Develop prioritized
listBioninformatics, Data Integration, and Data RepresentationSteve
Sherry, NCBI Develop consensus plan for experimental
characterization of Reference MaterialsDevelop plan for integrating
experimental data and forming consensus variant calls and
confidence estimates Develop consensus plan for data
representationPerformance Metrics & Figures of MeritDeanna
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 MaterialsTuesday 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 OverviewPlease
Note Topic #1: Moving beyond the 'easy' variants and regions of the
genome Topic #2: Selecting future genomes for Reference
Materialsotherwise. Please use #giabFirst meeting of the Steering
as the hashtag Committee (others adjourn). 10. NIST Reference
Materials Pilot RM - NA12878Personal 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 doesnt 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 productsPGP 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
