Clinical application of ultra high throughput sequencing (UHTS) or "Next Generation Sequencing" for hereditary genetic diseases and oncology is rapidly growing. At present, there are no widely accepted genomic standards or quantitative performance metrics for confidence in variant calling. These are needed to achieve the confidence in measurement results expected for sound, reproducible research and regulated applications in the clinic. On April 13, 2012, NIST convened the workshop "Genome in a Bottle" to initiate a consortium to develop the reference materials, reference methods, and reference data needed to assess confidence in human genome variant calls. A principal motivation for this consortium is to develop widely accepted reference materials and accompanying performance metrics to provide a strong scientific foundation for the development of regulations and professional standards for clinical sequencing.
At present, we expect the consortium to have four working groups with the listed responsibilities:
(1) Reference Material (RM) Selection and Design
select appropriate cell lines for whole genome RMs and design synthetic DNA constructs that could be spiked-in to samples
(2) Measurements for Reference Material Characterization,
design and carry out experiments to characterize the RMs using multiple sequencing methods, other methods, and validation of selected variants using orthogonal technologies
(3) Bioinformatics, Data Integration, and Data Representation
develop methods to analyze and integrate the data for each RM, as well as select appropriate formats to represent the data.
(4) Performance Metrics and Figures of Merit
develop useful performance metrics and figures of merit that can be obtained through measurement of the RMs.
The products of these working groups will be a set of well-characterized whole genome and synthetic DNA RMs along with the methods (documentary standards) and reference data necessary for use of the RMs. These products will be designed to help enable translation of whole genome sequencing to clinical applications by providing widely accepted materials, methods, and data for performance assessment.
An open meeting will be held August 16-17, 2012 at the National Institute of Standards and Technology in Gaithersburg, MD to receive public comment on this proposed work plan for the "Genome in a Bottle" Consortium.