Chapter 23 - Genomic Reference Materials for Clinical Applications

Abstract

Reference materials are well-characterized, homogeneous, and stable samples that can be used to understand measurement performance. The Genome in a Bottle Consortium is developing whole human genome DNA reference materials from large batches of DNA extracted from cell lines to support clinical translation of whole human genome sequencing. This DNA will be characterized using multiple sequencing and bioinformatics methods for single nucleotide polymorphisms, indels, structural variants, and haplotype phasing across the whole genome. Characterization of the reference material will be done with methods being developed by The Consortium to integrate information from multiple data sets to form highly confident genotype calls. These highly confident genotype calls can then be used by clinical and research laboratories to understand and optimize performance of library preparation, sequencing, and bioinformatics methods for genome sequencing, and can be used by accreditation and regulatory bodies to evaluate performance. Because the reference materials are homogeneous and stable, they will be able to be used to assess and compare sequencing performance with different methods over time, even as sequencing technologies and bioinformatics methods rapidly improve.