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Sequencing of human genomes with nanopore technology

Author

Listed:
  • Rory Bowden

    (University of Oxford)

  • Robert W. Davies

    (Genomics plc
    Hospital for Sick Children)

  • Andreas Heger

    (Genomics plc)

  • Alistair T. Pagnamenta

    (University of Oxford
    National Institute for Health Research Oxford Biomedical Research Centre)

  • Mariateresa Cesare

    (University of Oxford)

  • Laura E. Oikkonen

    (University of Oxford)

  • Duncan Parkes

    (University of Oxford)

  • Colin Freeman

    (University of Oxford)

  • Fatima Dhalla

    (Oxford University Hospitals
    University of Oxford)

  • Smita Y. Patel

    (Oxford University Hospitals
    National Institute for Health Research Oxford Biomedical Research Centre)

  • Niko Popitsch

    (University of Oxford
    National Institute for Health Research Oxford Biomedical Research Centre
    St. Anna Kinderkrebsforschung)

  • Camilla L. C. Ip

    (University of Oxford)

  • Hannah E. Roberts

    (University of Oxford)

  • Silvia Salatino

    (University of Oxford)

  • Helen Lockstone

    (University of Oxford)

  • Gerton Lunter

    (University of Oxford
    Genomics plc)

  • Jenny C. Taylor

    (University of Oxford
    National Institute for Health Research Oxford Biomedical Research Centre)

  • David Buck

    (University of Oxford)

  • Michael A. Simpson

    (Genomics plc)

  • Peter Donnelly

    (University of Oxford
    Genomics plc
    University of Oxford)

Abstract

Whole-genome sequencing (WGS) is becoming widely used in clinical medicine in diagnostic contexts and to inform treatment choice. Here we evaluate the potential of the Oxford Nanopore Technologies (ONT) MinION long-read sequencer for routine WGS by sequencing the reference sample NA12878 and the genome of an individual with ataxia-pancytopenia syndrome and severe immune dysregulation. We develop and apply a novel reference panel-free analytical method to infer and then exploit phase information which improves single-nucleotide variant (SNV) calling performance from otherwise modest levels. In the clinical sample, we identify and directly phase two non-synonymous de novo variants in SAMD9L, (OMIM #159550) inferring that they lie on the same paternal haplotype. Whilst consensus SNV-calling error rates from ONT data remain substantially higher than those from short-read methods, we demonstrate the substantial benefits of analytical innovation. Ongoing improvements to base-calling and SNV-calling methodology must continue for nanopore sequencing to establish itself as a primary method for clinical WGS.

Suggested Citation

  • Rory Bowden & Robert W. Davies & Andreas Heger & Alistair T. Pagnamenta & Mariateresa Cesare & Laura E. Oikkonen & Duncan Parkes & Colin Freeman & Fatima Dhalla & Smita Y. Patel & Niko Popitsch & Cami, 2019. "Sequencing of human genomes with nanopore technology," Nature Communications, Nature, vol. 10(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09637-5
    DOI: 10.1038/s41467-019-09637-5
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    Cited by:

    1. Helen M. Gunter & Scott E. Youlten & Andre L. M. Reis & Tim McCubbin & Bindu Swapna Madala & Ted Wong & Igor Stevanovski & Arcadi Cipponi & Ira W. Deveson & Nadia S. Santini & Sarah Kummerfeld & Peter, 2024. "A universal molecular control for DNA, mRNA and protein expression," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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