Language
English
Publication Date
10-19-2024
Journal
Nature Communications
DOI
10.1038/s41467-024-53260-y
PMID
39424793
PMCID
PMC11489684
PubMedCentral® Posted Date
10-19-2024
PubMedCentral® Full Text Version
Post-print
Abstract
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.
Keywords
Humans, Genome, Human, Software, Genomics, Sequence Analysis, DNA, Benchmarking, High-Throughput Nucleotide Sequencing, Genomics, Databases, Genome, Standards, Genomic analysis
Published Open-Access
yes
Recommended Citation
Dwarshuis, Nathan; Kalra, Divya; McDaniel, Jennifer; et al., "The GIAB Genomic Stratifications Resource for Human Reference Genomes" (2024). Faculty and Staff Publications. 2300.
https://digitalcommons.library.tmc.edu/baylor_docs/2300
Included in
Biological Phenomena, Cell Phenomena, and Immunity Commons, Biomedical Informatics Commons, Genetics and Genomics Commons, Medical Genetics Commons, Medical Molecular Biology Commons, Medical Specialties Commons