Document Type

Article

Publication Date

5-2022

Identifier

DOI: 10.1016/j.xgen.2022.100128; PMCID: PMC9706577

Abstract

Genome in a Bottle benchmarks are widely used to help validate clinical sequencing pipelines and develop variant calling and sequencing methods. Here we use accurate linked and long reads to expand benchmarks in 7 samples to include difficult-to-map regions and segmental duplications that are challenging for short reads. These benchmarks add more than 300,000 SNVs and 50,000 insertions or deletions (indels) and include 16% more exonic variants, many in challenging, clinically relevant genes not covered previously, such as PMS2. For HG002, we include 92% of the autosomal GRCh38 assembly while excluding regions problematic for benchmarking small variants, such as copy number variants, that should not have been in the previous version, which included 85% of GRCh38. It identifies eight times more false negatives in a short read variant call set relative to our previous benchmark. We demonstrate that this benchmark reliably identifies false positives and false negatives across technologies, enabling ongoing methods development.

Journal Title

Cell Genom

Volume

2

Issue

5

Comments

This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Publisher's Link: https://www.sciencedirect.com/science/article/pii/S2666979X2200057X?via%3Dihub

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