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Aug2015 salit standards architecture
This document discusses standards for characterizing whole genome sequencing. It describes the Genome in a Bottle Consortium which aims to develop reference materials, data, methods and performance metrics for whole genome variant calling. The consortium has characterized the genome of sample NA12878 and is working on Ashkenazim and Asian trios. The document outlines the need for standards and evidence regarding accurate and unbiased sequencing, sequence bioinformatics processing, and functional and clinical variant annotation in order to assess analytical and technical performance of whole genome sequencing for clinical use.
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Aug2015 salit standards architecture
- 1. Standards for Characterizing Whole-GenomeSequencing Marc Salit, NIST/JIMB GIAB Workshop – August 28, 2015
- 2. Enterprise WGS TestArchitecture Preanalytical Sequencing Sequence Bioinformatics Functional Variant Annotation Clinical Variant Knowledgebase Query Clinical Interpretation Reporting EHR Archival
- 3. Genome in aBottle Consortium Whole Genome Variant Calling Sample gDNA isolation Library Prep Sequencing Alignment/Mapping Variant Calling Confidence Estimates Downstream Analysis • gDNA reference materials to evaluate performance – materials certified for their variants against a reference sequence, with confidence estimates • established consortium to develop reference materials, data, methods, performance metrics • Characterized Pilot Genome NA12878 • Ashkenazim Trio, Asian Trio from PGP in process genericmeasurementprocess
- 4. Analytical/Technical Performance Assessment Preanalytical Sequencing Sequence Bioinformatics Functional Variant Annotation ClinicalVariant Knowledgebase Query Clinical Interpretation Reporting EHR Archival
- 5. Sequencing from DNA ->Raw Sequence Data Evidence to be established Standards/Evidenc e developing Stakeholders Example Knowledge Gaps Accurate (unbiased) sequencing Fit-for-purpose characteristics Well-characterized genomic DNA reference materials Documentary standard describing sequencing characteristics appropriate for different clinical indications Standards Labs Clinical labs Sequencing Technology Developers Academic Labs developing methods Genome Centers Sequencing “difficult” regions Platform artifacts High quality benchmark genomes Performance expectations (sensitivity/specific ity)
- 6. Sequence Bioinformatics Raw SequenceData -> VCF Evidence to be established Standards/Evidence developing Stakeholders Example Knowledge Gaps Unbiased processing of sequence data (mapping/asse mbly) Accurate variant calling Accurate and unambiguous representation, interoperability Protocols to critically evaluate processes, informed by platform idiosyncrasies Data representation standards Reference data/implementation: benchmark VCF files Reference software to evaluate VCF files Standards Labs Clinical labs Sequencing Technology Developers Academic Labs developing methods Genome Centers Assembly/mapping in “difficult” regions Artifacts Benchmark genomes Performance expectations SDO and Accreditation body fluency with bioinformatics
- 7. Analytical/Technical Performance Assessment Preanalytical Sequencing Sequence Bioinformatics Functional Variant Annotation ClinicalVariant Knowledgebase Query Clinical Interpretation Reporting EHR Archival