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Direct detection of 8-oxo-dG using nanopore sequencing

Author

Listed:
  • Marc Pagès-Gallego

    (Utrecht University
    Oncode Institute)

  • Daan M. K. van Soest

    (Utrecht University)

  • Nicolle J. M. Besselink

    (Utrecht University
    Oncode Institute
    Princess Máxima Center for Pediatric Oncology)

  • Roy Straver

    (Utrecht University
    Oncode Institute)

  • Janneke P. Keijer

    (Utrecht University)

  • Carlo Vermeulen

    (Utrecht University
    Oncode Institute)

  • Alessio Marcozzi

    (Cyclomics)

  • Markus J. van Roosmalen

    (Oncode Institute
    Princess Máxima Center for Pediatric Oncology)

  • Ruben van Boxtel

    (Oncode Institute
    Princess Máxima Center for Pediatric Oncology)

  • Boudewijn M. T. Burgering

    (Utrecht University
    Oncode Institute)

  • Tobias B. Dansen

    (Utrecht University)

  • Jeroen Ridder

    (Utrecht University
    Oncode Institute)

Abstract

Genomic DNA is under constant oxidative damage, with 8-oxo-7,8-dihydro-2’-deoxyguanosine (8-oxo-dG) being the prominent lesion linked to mutagenesis, epigenetics, and gene regulation. Existing methods to detect 8-oxo-dG rely on indirect approaches, while nanopore sequencing enables direct detection of base modifications. A model for 8-oxo-dG detection is currently missing due to the lack of training data. Here, we develop a strategy using synthetic oligos to generate long, 8-oxo-dG context-variable DNA molecules for deep learning and nanopore sequencing. Our training approach addresses the rarity of 8-oxo-dG relative to guanine, enabling specific detection. Applied to a tissue culture model of oxidative damage, our method reveals uneven genomic 8-oxo-dG distribution, dissimilar context pattern to C>A mutations, and local 5-mC depletion. This dual measurement of 5-mC and 8-oxo-dG at single-molecule resolution uncovers new insights into their interplay. Our approach also provides a general framework for detecting other rare DNA modifications using synthetic DNA and nanopore sequencing.

Suggested Citation

  • Marc Pagès-Gallego & Daan M. K. van Soest & Nicolle J. M. Besselink & Roy Straver & Janneke P. Keijer & Carlo Vermeulen & Alessio Marcozzi & Markus J. van Roosmalen & Ruben van Boxtel & Boudewijn M. T, 2025. "Direct detection of 8-oxo-dG using nanopore sequencing," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60391-3
    DOI: 10.1038/s41467-025-60391-3
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    References listed on IDEAS

    as
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