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2014 agbt giab_progress update


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2014 agbt giab_progress update

  1. 1. Genome in a Bottle Consortium: Update on a Public-Private-Academic Consortium Developing a Standards Infrastructure for Human Genome Sequencing Marc Salit1,2, Sarah A. Munro1,2, Justin Zook1, Genome in a Bottle Consortium (1) National Institute of Standards and Technology, Gaithersburg, MD 20899; (2) National Institute of Standards and Technology Advances in Biomedical Measurement Sciences Program at Stanford University, Stanford, CA 94035 Reference Material Selection and Design Group Overview In 2012, NIST convened the Genome in a Bottle Consortium to develop the metrology infrastructure needed to enable confidence in human whole genome variant calls. Consortium products will include: • Well-characterized whole genome and synthetic DNA Reference Materials (RMs) • Reference data associated with the RMs • Reference methods (Comparison tools, documentary standards) Reference Materials Sample Preparation Variant List, Performance metrics Sequencing • Personal Genome Project samples – consent for commercialization • Ashkenazi Jewish trio • East Asian trio • Looking for additional large family • Supporting interlaboratory analysis of potential commercial Alien Barcode reference materials, new participants welcome Mutation of • COLO-829/COLO 829BL cancer/normal cell line Interest • Artificial structures as spike-ins for point mutations or more complex structural variants Point Mutation Control Plasmids from • FFPE samples based on RM cell lines M. Williams et al. Frederick National Laboratory for Cancer Research Bioinformatics These Genome in a Bottle products will enable translation of whole genome sequencing to clinical applications. Expected use cases of these products include: • Enable regulated applications • Validation, QC, proficiency testing • Identify and quantify sources of bias & variability • Optimize measurement technologies • Resolve structural variants • Improve reference assembly • Integrate data from multiple platforms New participants are welcome to join: Measurements for Reference Material Characterization Group • Initiated experiments to characterize pilot RM (NA12878) • 6 institutions have signed Material Transfer Agreements with NIST for pilot RM • Other institutions are welcome to contact NIST to help with sequencing PGP trio RMs • Cell lines are also available from Coriell Vial of ~10 g of NA12878 cell line genomic DNA Multiple measurement technologies and modes e.g. • Illumina • Life Technologies • Complete Genomics • Pacific Biosciences • BioNano Genomics Milestones Worked with Coriell to develop ~8300 vials of pilot RM from NA12878 cell line; samples received by NIST April 2013 NCBI-team led development of Genome in a Bottle FTP site containing curated data associated with RMs ( NIST-led team prepared Data Integration Manuscript; preprint available on arXiv ( in press in Nature Biotechnology. Selected next 2 families for genome RMs from PGP collection; DNA samples at NIST February 2014 Decided on governance policies including formation of a steering committee and a data release policy based on Fort Lauderdale Principles, August 2013 Pilot RM release planned for May 2014; simultaneous release of pilot RM genotype calls How you can get involved: • • • • • • Sequencing/analyzing the new Personal Genome Project trios Help with Structural Variant calls Help with analyzing data from long-read technologies Attend our biannual workshops (January in CA, August in MD) Help develop methods to measure performance using our wellcharacterized genomes Use our integrated SNP/indel genotypes for NA12878 and give us feedback Bioinformatics, Data Integration, and Data Representation Group • Developed data integration methods and genotype calls for NA12878 • Multi-platform method • NIST-led team preprint on arXiv, accepted by Nature Biotechnology • Pedigree methods • Real Time Genomics (RTG) • Illumina Platinum Genomes • Established data release and QC policies, FTP site with curated data Real Time Genomics pedigree-based method courtesy of Francisco De La Vega Performance Metrics Group • Integration of software from partners: • GCAT (Genome Comparison & Analytic Testing) tool enables mapping and variant call comparisons in exome, NIST analysis results publicly available here • NCBI/CDC GeT-RM browser supports visualization of variant calls; includes NIST highly confident genotypes track • RTG tool vcfeval for complex variants • VCFComparator • HSPH bcbio.variation tools