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Analysis and benchmarking of small and large genomic variants across tandem repeats.

作者信息

English Adam C, Dolzhenko Egor, Ziaei Jam Helyaneh, McKenzie Sean K, Olson Nathan D, De Coster Wouter, Park Jonghun, Gu Bida, Wagner Justin, Eberle Michael A, Gymrek Melissa, Chaisson Mark J P, Zook Justin M, Sedlazeck Fritz J

机构信息

Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.

Pacific Biosciences of California, Menlo Park, CA, USA.

出版信息

Nat Biotechnol. 2025 Mar;43(3):431-442. doi: 10.1038/s41587-024-02225-z. Epub 2024 Apr 26.


DOI:10.1038/s41587-024-02225-z
PMID:38671154
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11952744/
Abstract

Tandem repeats (TRs) are highly polymorphic in the human genome, have thousands of associated molecular traits and are linked to over 60 disease phenotypes. However, they are often excluded from at-scale studies because of challenges with variant calling and representation, as well as a lack of a genome-wide standard. Here, to promote the development of TR methods, we created a catalog of TR regions and explored TR properties across 86 haplotype-resolved long-read human assemblies. We curated variants from the Genome in a Bottle (GIAB) HG002 individual to create a TR dataset to benchmark existing and future TR analysis methods. We also present an improved variant comparison method that handles variants greater than 4 bp in length and varying allelic representation. The 8.1% of the genome covered by the TR catalog holds ~24.9% of variants per individual, including 124,728 small and 17,988 large variants for the GIAB HG002 'truth-set' TR benchmark. We demonstrate the utility of this pipeline across short-read and long-read technologies.

摘要

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引用本文的文献

[1]
TRsv: simultaneous detection of tandem repeat variations, structural variations, and short indels using long read sequencing data.

Genome Biol. 2025-8-20

[2]
Whole-genome variant detection in long-read sequencing data from ultra-low input patient samples.

medRxiv. 2025-7-27

[3]
The Platinum Pedigree: a long-read benchmark for genetic variants.

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[4]
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bioRxiv. 2025-5-24

[5]
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Genes (Basel). 2025-3-30

[6]
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[7]
Analysis of targeted and whole genome sequencing of PacBio HiFi reads for a comprehensive genotyping of gene-proximal and phenotype-associated Variable Number Tandem Repeats.

PLoS Comput Biol. 2025-4-7

[8]
K-mer analysis of long-read alignment pileups for structural variant genotyping.

Nat Commun. 2025-4-4

[9]
Development of Publicly Available Forensic DNA Sequence Mixture Data.

Genes (Basel). 2025-3-12

[10]
STRchive: a dynamic resource detailing population-level and locus-specific insights at tandem repeat disease loci.

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本文引用的文献

[1]
Small polymorphisms are a source of ancestral bias in structural variant breakpoint placement.

Genome Res. 2024-2-7

[2]
Characterization and visualization of tandem repeats at genome scale.

Nat Biotechnol. 2024-10

[3]
vcfdist: accurately benchmarking phased small variant calls in human genomes.

Nat Commun. 2023-12-9

[4]
A deep population reference panel of tandem repeat variation.

Nat Commun. 2023-10-23

[5]
Genomic variant benchmark: if you cannot measure it, you cannot improve it.

Genome Biol. 2023-10-5

[6]
The complete sequence of a human Y chromosome.

Nature. 2023-9

[7]
vamos: variable-number tandem repeats annotation using efficient motif sets.

Genome Biol. 2023-7-27

[8]
TRviz: a Python library for decomposing and visualizing tandem repeat sequences.

Bioinform Adv. 2023-4-26

[9]
A draft human pangenome reference.

Nature. 2023-5

[10]
TRASH: Tandem Repeat Annotation and Structural Hierarchy.

Bioinformatics. 2023-5-4

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