Title | Multiscale analysis of pangenomes enables improved representation of genomic diversity for repetitive and clinically relevant genes. |
Publication Type | Journal Article |
Year of Publication | 2023 |
Authors | Chin, C-S, Behera, S, Khalak, A, Sedlazeck, FJ, Sudmant, PH, Wagner, J, Zook, JM |
Journal | Nat Methods |
Volume | 20 |
Issue | 8 |
Pagination | 1213-1221 |
Date Published | 2023 Aug |
ISSN | 1548-7105 |
Keywords | Genome, Human, Genomics, Humans, Major Histocompatibility Complex, Male |
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. |
DOI | 10.1038/s41592-023-01914-y |
Alternate Journal | Nat Methods |
PubMed ID | 37365340 |
PubMed Central ID | PMC10406601 |
Grant List | R35 GM142916 / GM / NIGMS NIH HHS / United States R35GM142916 / GM / NIGMS NIH HHS / United States 1U01HG011758-01 / HG / NHGRI NIH HHS / United States UM1 HG008898 / HG / NHGRI NIH HHS / United States U01 HG011758 / HG / NHGRI NIH HHS / United States |
Multiscale analysis of pangenomes enables improved representation of genomic diversity for repetitive and clinically relevant genes.
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