K-Mer Analysis of Long-Read Alignment Pileups for Structural Variant Genotyping

Authors

Adam C English
Fabio Cunial
Ginger A Metcalf
Richard A Gibbs
Fritz J Sedlazeck

Language

English

Publication Date

4-4-2025

Journal

Nature Communications

DOI

10.1038/s41467-025-58577-w

PMID

40185777

PMCID

PMC11971316

PubMedCentral® Posted Date

4-4-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Accurately genotyping structural variant (SV) alleles is crucial to genomics research. We present a novel method (kanpig) for genotyping SVs that leverages variant graphs and k-mer vectors to rapidly generate accurate SV genotypes. Benchmarking against the latest SV datasets shows kanpig achieves a single-sample genotyping concordance of 82.1%, significantly outperforming existing tools, which average 66.3%. We explore kanpig's use for multi-sample projects by testing on 47 genetically diverse samples and find kanpig accurately genotypes complex loci (e.g. SVs neighboring other SVs), and produces higher genotyping concordance than other tools. Kanpig requires only 43 seconds to process a single sample's 20x long-reads and can be run on PacBio or Oxford Nanopore long-reads.

Keywords

Genotyping Techniques, Humans, Genotype, Genomics, Alleles, Genomic Structural Variation, High-Throughput Nucleotide Sequencing, Software, Sequence Analysis, DNA, Sequence Alignment, Algorithms, Data processing, Genotype

Published Open-Access

yes

Recommended Citation

English, Adam C; Cunial, Fabio; Metcalf, Ginger A; et al., "K-Mer Analysis of Long-Read Alignment Pileups for Structural Variant Genotyping" (2025). Faculty and Staff Publications. 5116.
https://digitalcommons.library.tmc.edu/baylor_docs/5116