Multiscale analysis of pangenomes enables improved representation of genomic diversity for repetitive and clinically relevant genes

Published

June 26, 2023

Author(s)

Chen-Shan Chin, Sairam Behera, Asif Khalak, Fritz Sedlazeck, Justin Wagner, Justin Zook

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.

Citation

Nature Methods

Volume

20

Pub Type

Journals

Download Paper

https://doi.org/10.1038/s41592-023-01914-y

Local Download

Keywords

genomics, pangenome graph, structural variation, de novo assembly

Citation

Chin, C. , Behera, S. , Khalak, A. , Sedlazeck, F. , Wagner, J. and Zook, J. (2023), Multiscale analysis of pangenomes enables improved representation of genomic diversity for repetitive and clinically relevant genes, Nature Methods, [online], https://doi.org/10.1038/s41592-023-01914-y, https://tsapps.nist.gov/publication/get_pdf.cfm?pub_id=935376 (Accessed October 9, 2025)