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Structural variant-based pangenome construction has low sensitivity to variability of haplotype-resolved bovine assemblies

Advantages of pangenomes over linear reference assemblies for genome research have recently been established. However, potential effects of sequence platform and assembly approach, or of combining assemblies created by different approaches, on pangenome construction have not been investigated. Here...

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Autores principales: Leonard, Alexander S., Crysnanto, Danang, Fang, Zih-Hua, Heaton, Michael P., Vander Ley, Brian L., Herrera, Carolina, Bollwein, Heinrich, Bickhart, Derek M., Kuhn, Kristen L., Smith, Timothy P. L., Rosen, Benjamin D., Pausch, Hubert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9156671/
https://www.ncbi.nlm.nih.gov/pubmed/35641504
http://dx.doi.org/10.1038/s41467-022-30680-2
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author Leonard, Alexander S.
Crysnanto, Danang
Fang, Zih-Hua
Heaton, Michael P.
Vander Ley, Brian L.
Herrera, Carolina
Bollwein, Heinrich
Bickhart, Derek M.
Kuhn, Kristen L.
Smith, Timothy P. L.
Rosen, Benjamin D.
Pausch, Hubert
author_facet Leonard, Alexander S.
Crysnanto, Danang
Fang, Zih-Hua
Heaton, Michael P.
Vander Ley, Brian L.
Herrera, Carolina
Bollwein, Heinrich
Bickhart, Derek M.
Kuhn, Kristen L.
Smith, Timothy P. L.
Rosen, Benjamin D.
Pausch, Hubert
author_sort Leonard, Alexander S.
collection PubMed
description Advantages of pangenomes over linear reference assemblies for genome research have recently been established. However, potential effects of sequence platform and assembly approach, or of combining assemblies created by different approaches, on pangenome construction have not been investigated. Here we generate haplotype-resolved assemblies from the offspring of three bovine trios representing increasing levels of heterozygosity that each demonstrate a substantial improvement in contiguity, completeness, and accuracy over the current Bos taurus reference genome. Diploid coverage as low as 20x for HiFi or 60x for ONT is sufficient to produce two haplotype-resolved assemblies meeting standards set by the Vertebrate Genomes Project. Structural variant-based pangenomes created from the haplotype-resolved assemblies demonstrate significant consensus regardless of sequence platform, assembler algorithm, or coverage. Inspecting pangenome topologies identifies 90 thousand structural variants including 931 overlapping with coding sequences; this approach reveals variants affecting QRICH2, PRDM9, HSPA1A, TAS2R46, and GC that have potential to affect phenotype.
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spelling pubmed-91566712022-06-02 Structural variant-based pangenome construction has low sensitivity to variability of haplotype-resolved bovine assemblies Leonard, Alexander S. Crysnanto, Danang Fang, Zih-Hua Heaton, Michael P. Vander Ley, Brian L. Herrera, Carolina Bollwein, Heinrich Bickhart, Derek M. Kuhn, Kristen L. Smith, Timothy P. L. Rosen, Benjamin D. Pausch, Hubert Nat Commun Article Advantages of pangenomes over linear reference assemblies for genome research have recently been established. However, potential effects of sequence platform and assembly approach, or of combining assemblies created by different approaches, on pangenome construction have not been investigated. Here we generate haplotype-resolved assemblies from the offspring of three bovine trios representing increasing levels of heterozygosity that each demonstrate a substantial improvement in contiguity, completeness, and accuracy over the current Bos taurus reference genome. Diploid coverage as low as 20x for HiFi or 60x for ONT is sufficient to produce two haplotype-resolved assemblies meeting standards set by the Vertebrate Genomes Project. Structural variant-based pangenomes created from the haplotype-resolved assemblies demonstrate significant consensus regardless of sequence platform, assembler algorithm, or coverage. Inspecting pangenome topologies identifies 90 thousand structural variants including 931 overlapping with coding sequences; this approach reveals variants affecting QRICH2, PRDM9, HSPA1A, TAS2R46, and GC that have potential to affect phenotype. Nature Publishing Group UK 2022-05-31 /pmc/articles/PMC9156671/ /pubmed/35641504 http://dx.doi.org/10.1038/s41467-022-30680-2 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Leonard, Alexander S.
Crysnanto, Danang
Fang, Zih-Hua
Heaton, Michael P.
Vander Ley, Brian L.
Herrera, Carolina
Bollwein, Heinrich
Bickhart, Derek M.
Kuhn, Kristen L.
Smith, Timothy P. L.
Rosen, Benjamin D.
Pausch, Hubert
Structural variant-based pangenome construction has low sensitivity to variability of haplotype-resolved bovine assemblies
title Structural variant-based pangenome construction has low sensitivity to variability of haplotype-resolved bovine assemblies
title_full Structural variant-based pangenome construction has low sensitivity to variability of haplotype-resolved bovine assemblies
title_fullStr Structural variant-based pangenome construction has low sensitivity to variability of haplotype-resolved bovine assemblies
title_full_unstemmed Structural variant-based pangenome construction has low sensitivity to variability of haplotype-resolved bovine assemblies
title_short Structural variant-based pangenome construction has low sensitivity to variability of haplotype-resolved bovine assemblies
title_sort structural variant-based pangenome construction has low sensitivity to variability of haplotype-resolved bovine assemblies
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9156671/
https://www.ncbi.nlm.nih.gov/pubmed/35641504
http://dx.doi.org/10.1038/s41467-022-30680-2
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