Publication Date

8-1-2023

Journal

Nature Methods

DOI

10.1038/s41592-023-01914-y

PMID

37365340

PMCID

PMC10406601

PubMedCentral® Posted Date

6-26-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Male, Humans, Genomics, Genome, Human, Major Histocompatibility Complex, Software, Genome assembly algorithms, Structural variation, Genome assembly algorithms

Abstract

Advancements in sequencing technologies and assembly methods enable the regular production of high-quality genome assemblies characterizing complex regions. However, challenges remain in efficiently interpreting variation at various scales, from smaller tandem repeats to megabase rearrangements, across many human genomes. We present a PanGenome Research Tool Kit (PGR-TK) enabling analyses of complex pangenome structural and haplotype variation at multiple scales. We apply the graph decomposition methods in PGR-TK to the class II major histocompatibility complex demonstrating the importance of the human pangenome for analyzing complicated regions. Moreover, we investigate the Y-chromosome genes, DAZ1/DAZ2/DAZ3/DAZ4, of which structural variants have been linked to male infertility, and X-chromosome genes OPN1LW and OPN1MW linked to eye disorders. We further showcase PGR-TK across 395 complex repetitive medically important genes. This highlights the power of PGR-TK to resolve complex variation in regions of the genome that were previously too complex to analyze.

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