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

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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Chin, C.-S., Behera, S., Khalak, A., Sedlazeck, F. J., Sudmant, P. H., Wagner, J., & Zook, J. M. (2023). Multiscale analysis of pangenomes enables improved representation of genomic diversity for repetitive and clinically relevant genes. Nature Methods, 20(8), 1213–1221. https://doi.org/10.1038/s41592-023-01914-y

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