The GIAB genomic stratifications resource for human reference genomes
Journal article, 2024
Despite the growing variety of sequencing and variant-calling tools, no workflow performs equally well across the entire human genome. Understanding context-dependent performance is critical for enabling researchers, clinicians, and developers to make informed tradeoffs when selecting sequencing hardware and software. Here we describe a set of “stratifications,” which are BED files that define distinct contexts throughout the genome. We define these for GRCh37/38 as well as the new T2T-CHM13 reference, adding many new hard-to-sequence regions which are critical for understanding performance as the field progresses. Specifically, we highlight the increase in hard-to-map and GC-rich stratifications in CHM13 relative to the previous references. We then compare the benchmarking performance with each reference and show the performance penalty brought about by these additional difficult regions in CHM13. Additionally, we demonstrate how the stratifications can track context-specific improvements over different platform iterations, using Oxford Nanopore Technologies as an example. The means to generate these stratifications are available as a snakemake pipeline at https://github.com/usnistgov/giab-stratifications. We anticipate this being useful in enabling precise risk-reward calculations when building sequencing pipelines for any of the commonly-used reference genomes.
Author
Nathan Dwarshuis
National Institute of Standards and Technology (NIST)
Divya Kalra
Baylor College of Medicine
Jennifer McDaniel
National Institute of Standards and Technology (NIST)
Philippe Sanio
University of Applied Sciences Upper Austria
Pilar Alvarez Jerez
University College London (UCL)
National Institutes of Health (NIH)
Bharati Jadhav
Icahn School of Medicine at Mount Sinai
Wenyu (Eddy) Huang
Rice University
Rajarshi Mondal
Pondicherry University
Ben Busby
DNA Nexus
Nathan D. Olson
National Institute of Standards and Technology (NIST)
Fritz J. Sedlazeck
Baylor College of Medicine
Rice University
Justin Wagner
National Institute of Standards and Technology (NIST)
Sina Majidian
Swiss Institute of Bioinformatics
University of Lausanne
Justin M. Zook
National Institute of Standards and Technology (NIST)
Nature Communications
2041-1723 (ISSN) 20411723 (eISSN)
Vol. 15 9029Subject Categories (SSIF 2025)
Bioinformatics (Computational Biology)
DOI
10.1038/s41467-024-53260-y