The Genome In A Bottle HG002 assembly-based variant benchmark set enables comprehensive benchmarking of small and structural variants.
- 1National Institute of Standards and Technology
Abstract
High-accuracy, high-resolution benchmark data are fundamental to improving the accuracy and generalizability of sequencing technologies and associated algorithms. Most existing benchmarks for DNA sequencing rely on mapping to a single linear reference, omitting inaccessible and highly repetitive complex genomic regions. Here, we present the Genome in a Bottle (GIAB) Consortium's HG002 v5.0q benchmark set, a more comprehensive variant benchmark derived from a fully phased, highly curated, and accurate diploid assembly of HG002. Our approach leverages recent advances in long-read sequencing and assembly to provide confident small- and structural-variant calls across previously inaccessible regions, including segmental duplications, homopolymers, tandem repeats, and complex immune loci. The v5.0 benchmark significantly expands the callable genome relative to v4.2.1, adding x200 Mbp of sequence and increasing variant detection by 18 % for small variants and 3-fold for structural variants compared to previous benchmarks. The benchmark regions include more variants in repetitive regions, including 1.2 x segmental duplications, 1.8 x tandem repeats, and 2.0 x homopolymers, compared to v4.2.1. Separate and combined small- and structural-variant benchmarks are available for three versions of the human reference genome (GRCh37, GRCh38, and CHM13). We validate the reliability of this benchmark set by comparing multiple sequencing technologies and variant calling pipelines and curating differences. The v5.0q benchmark provides a critical resource for the development and validation of next-generation sequencing technologies and analysis methods.
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BibTeX
@misc{olson2026genome,
title = {{The Genome In A Bottle HG002 assembly-based variant benchmark set enables comprehensive benchmarking of small and structural variants.}},
author = {N. D. Olson and N. Dwarshuis and N. F. Hansen and S. Koren and A. Rhie and J. H. McDaniel and J. Wagner and G. Berry and K. Shafin and A. English and C. T. Saunders and R. Kundu and J. M. Holt and D. Freed and A. A. Abdulkadir and C. Daniels and S. Majidian and L. F. Paulin and F. J. Sedlazeck and M. Fleharty and Y. Gao and L. Denti and L. Brambrink and A. Carroll and P.-C. Chang and D. E. Cook and A. Kolesnikov and S. Catreux and C. Edlund and J. Han and L. Murray and Y. Qiu and M. Rossi and K. Scheffler and S. Truong and Y. Wang and R. Chikhi and C. Flores and D. Jaspez and J. M. Lorenzo-Salazar and A. Munoz-Barrera and L. A. Rubio-Rodriguez and M.-J. Lin and K. Vaddadi and Lan},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.23.752440},
url = {https://www.biorxiv.org/content/10.64898/2026.09.23.752440v1},
note = {CC0},
}
RIS
TY - UNPB
TI - The Genome In A Bottle HG002 assembly-based variant benchmark set enables comprehensive benchmarking of small and structural variants.
AU - N. D. Olson
AU - N. Dwarshuis
AU - N. F. Hansen
AU - S. Koren
AU - A. Rhie
AU - J. H. McDaniel
AU - J. Wagner
AU - G. Berry
AU - K. Shafin
AU - A. English
AU - C. T. Saunders
AU - R. Kundu
AU - J. M. Holt
AU - D. Freed
AU - A. A. Abdulkadir
AU - C. Daniels
AU - S. Majidian
AU - L. F. Paulin
AU - F. J. Sedlazeck
AU - M. Fleharty
AU - Y. Gao
AU - L. Denti
AU - L. Brambrink
AU - A. Carroll
AU - P.-C. Chang
AU - D. E. Cook
AU - A. Kolesnikov
AU - S. Catreux
AU - C. Edlund
AU - J. Han
AU - L. Murray
AU - Y. Qiu
AU - M. Rossi
AU - K. Scheffler
AU - S. Truong
AU - Y. Wang
AU - R. Chikhi
AU - C. Flores
AU - D. Jaspez
AU - J. M. Lorenzo-Salazar
AU - A. Munoz-Barrera
AU - L. A. Rubio-Rodriguez
AU - M.-J. Lin
AU - K. Vaddadi
AU - Lan
PY - 2026
DA - 2026/09/23
PB - bioRxiv
DO - 10.64898/2026.09.23.752440
UR - https://www.biorxiv.org/content/10.64898/2026.09.23.752440v1
AB - High-accuracy, high-resolution benchmark data are fundamental to improving the accuracy and generalizability of sequencing technologies and associated algorithms. Most existing benchmarks for DNA sequencing rely on mapping to a single linear reference, omitting inaccessible and highly repetitive complex genomic regions. Here, we present the Genome in a Bottle (GIAB) Consortium's HG002 v5.0q benchmark set, a more comprehensive variant benchmark derived from a fully phased, highly curated, and accurate diploid assembly of HG002. Our approach leverages recent advances in long-read sequencing and assembly to provide confident small- and structural-variant calls across previously inaccessible regions, including segmental duplications, homopolymers, tandem repeats, and complex immune loci. The v5.0 benchmark significantly expands the callable genome relative to v4.2.1, adding x200 Mbp of sequence and increasing variant detection by 18 % for small variants and 3-fold for structural variants compared to previous benchmarks. The benchmark regions include more variants in repetitive regions, including 1.2 x segmental duplications, 1.8 x tandem repeats, and 2.0 x homopolymers, compared to v4.2.1. Separate and combined small- and structural-variant benchmarks are available for three versions of the human reference genome (GRCh37, GRCh38, and CHM13). We validate the reliability of this benchmark set by comparing multiple sequencing technologies and variant calling pipelines and curating differences. The v5.0q benchmark provides a critical resource for the development and validation of next-generation sequencing technologies and analysis methods.
ER -