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Detecting m6A at single-molecular resolution via direct RNA sequencing and realistic training data

Author

Listed:
  • Adrian Chan

    (University of Heidelberg)

  • Isabel S. Naarmann-de Vries

    (University of Heidelberg
    German Centre for Cardiovascular Research (DZHK)-Partner Site Heidelberg/Mannheim)

  • Carolin P. M. Scheitl

    (University of Würzburg)

  • Claudia Höbartner

    (University of Würzburg)

  • Christoph Dieterich

    (University of Heidelberg
    German Centre for Cardiovascular Research (DZHK)-Partner Site Heidelberg/Mannheim)

Abstract

Direct RNA sequencing offers the possibility to simultaneously identify canonical bases and epi-transcriptomic modifications in each single RNA molecule. Thus far, the development of computational methods has been hampered by the lack of biologically realistic training data that carries modification labels at molecular resolution. Here, we report on the synthesis of such samples and the development of a bespoke algorithm, mAFiA (m6A Finding Algorithm), that accurately detects single m6A nucleotides in both synthetic RNAs and natural mRNA on single read level. Our approach uncovers distinct modification patterns in single molecules that would appear identical at the ensemble level. Compared to existing methods, mAFiA also demonstrates improved accuracy in measuring site-level m6A stoichiometry in biological samples.

Suggested Citation

  • Adrian Chan & Isabel S. Naarmann-de Vries & Carolin P. M. Scheitl & Claudia Höbartner & Christoph Dieterich, 2024. "Detecting m6A at single-molecular resolution via direct RNA sequencing and realistic training data," Nature Communications, Nature, vol. 15(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47661-2
    DOI: 10.1038/s41467-024-47661-2
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    References listed on IDEAS

    as
    1. Casslynn W. Q. Koh & Yeek Teck Goh & W. S. Sho Goh, 2019. "Atlas of quantitative single-base-resolution N6-methyl-adenine methylomes," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
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