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GraphTyper2 enables population-scale genotyping of structural variation using pangenome graphs

Author

Listed:
  • Hannes P. Eggertsson

    (deCODE genetics/Amgen Inc.
    University of Iceland)

  • Snaedis Kristmundsdottir

    (deCODE genetics/Amgen Inc.
    Reykjavik University)

  • Doruk Beyter

    (deCODE genetics/Amgen Inc.)

  • Hakon Jonsson

    (deCODE genetics/Amgen Inc.)

  • Astros Skuladottir

    (deCODE genetics/Amgen Inc.)

  • Marteinn T. Hardarson

    (deCODE genetics/Amgen Inc.)

  • Daniel F. Gudbjartsson

    (deCODE genetics/Amgen Inc.
    University of Iceland)

  • Kari Stefansson

    (deCODE genetics/Amgen Inc.
    University of Iceland)

  • Bjarni V. Halldorsson

    (deCODE genetics/Amgen Inc.
    Reykjavik University)

  • Pall Melsted

    (deCODE genetics/Amgen Inc.
    University of Iceland)

Abstract

Analysis of sequence diversity in the human genome is fundamental for genetic studies. Structural variants (SVs) are frequently omitted in sequence analysis studies, although each has a relatively large impact on the genome. Here, we present GraphTyper2, which uses pangenome graphs to genotype SVs and small variants using short-reads. Comparison to the syndip benchmark dataset shows that our SV genotyping is sensitive and variant segregation in families demonstrates the accuracy of our approach. We demonstrate that incorporating public assembly data into our pipeline greatly improves sensitivity, particularly for large insertions. We validate 6,812 SVs on average per genome using long-read data of 41 Icelanders. We show that GraphTyper2 can simultaneously genotype tens of thousands of whole-genomes by characterizing 60 million small variants and half a million SVs in 49,962 Icelanders, including 80 thousand SVs with high-confidence.

Suggested Citation

  • Hannes P. Eggertsson & Snaedis Kristmundsdottir & Doruk Beyter & Hakon Jonsson & Astros Skuladottir & Marteinn T. Hardarson & Daniel F. Gudbjartsson & Kari Stefansson & Bjarni V. Halldorsson & Pall Me, 2019. "GraphTyper2 enables population-scale genotyping of structural variation using pangenome graphs," Nature Communications, Nature, vol. 10(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13341-9
    DOI: 10.1038/s41467-019-13341-9
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    1. Aimee M. Deaton & Aditi Dubey & Lucas D. Ward & Peter Dornbos & Jason Flannick & Elaine Yee & Simina Ticau & Leila Noetzli & Margaret M. Parker & Rachel A. Hoffing & Carissa Willis & Mollie E. Plekan , 2022. "Rare loss of function variants in the hepatokine gene INHBE protect from abdominal obesity," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    2. Sock Hoai Chan & Yasmin Bylstra & Jing Xian Teo & Jyn Ling Kuan & Nicolas Bertin & Mar Gonzalez-Porta & Maxime Hebrard & Roberto Tirado-Magallanes & Joanna Hui Juan Tan & Justin Jeyakani & Zhihui Li &, 2022. "Analysis of clinically relevant variants from ancestrally diverse Asian genomes," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    3. Marsha M. Wheeler & Adrienne M. Stilp & Shuquan Rao & Bjarni V. Halldórsson & Doruk Beyter & Jia Wen & Anna V. Mihkaylova & Caitlin P. McHugh & John Lane & Min-Zhi Jiang & Laura M. Raffield & Goo Jun , 2022. "Whole genome sequencing identifies structural variants contributing to hematologic traits in the NHLBI TOPMed program," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    4. Cristian Groza & Carl Schwendinger-Schreck & Warren A. Cheung & Emily G. Farrow & Isabelle Thiffault & Juniper Lake & William B. Rizzo & Gilad Evrony & Tom Curran & Guillaume Bourque & Tomi Pastinen, 2024. "Pangenome graphs improve the analysis of structural variants in rare genetic diseases," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    5. Max Lundberg & Alexander Mackintosh & Anna Petri & Staffan Bensch, 2023. "Inversions maintain differences between migratory phenotypes of a songbird," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    6. Joanna Hui Juan Tan & Zhihui Li & Mar Gonzalez Porta & Ramesh Rajaby & Weng Khong Lim & Ye An Tan & Rodrigo Toro Jimenez & Renyi Teo & Maxime Hebrard & Jack Ling Ow & Shimin Ang & Justin Jeyakani & Ya, 2024. "A Catalogue of Structural Variation across Ancestrally Diverse Asian Genomes," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    7. H. Serhat Tetikol & Deniz Turgut & Kubra Narci & Gungor Budak & Ozem Kalay & Elif Arslan & Sinem Demirkaya-Budak & Alexey Dolgoborodov & Duygu Kabakci-Zorlu & Vladimir Semenyuk & Amit Jain & Brandi N., 2022. "Pan-African genome demonstrates how population-specific genome graphs improve high-throughput sequencing data analysis," Nature Communications, Nature, vol. 13(1), pages 1-11, December.

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