ModiDeC: a multi-RNA modification classifier for direct nanopore sequencing.

Journal: Nucleic acids research
Published Date:

Abstract

RNA modifications play a crucial role in various cellular functions. Here, we present ModiDeC, a deep-learning-based classifier able to identify and distinguish multiple RNA modifications (N6-methyladenosine, inosine, pseudouridine, 2'-O-methylguanosine, and N1-methyladenosine) using direct RNA sequencing. Alongside ModiDeC, we provide an extensive database of in vitro-transcribed and synthetic sequences generated with both the new RNA004 chemistry and the old RNA002 kit. We show that RNA modifications can be accurately recognized and distinguished across different sequence motifs using synthetic data as well as in HEK293T cells and human blood samples. ModiDeC comes with a graphical user interface and an Epi2ME pipeline that allows easy customization and adaptation to specific research questions, such as learning and classifying additional RNA modifications and further sequence motifs. The reproducibility across samples, together with the low rate of false positives, underscores the potential of ModiDeC as a powerful tool for advancing the analysis of the epitranscriptome and RNA modification.

Authors

  • Nicolò Alagna
    Institute of Human Genetics, University Medical Center, Mainz, Germany.
  • Stefan Mündnich
    Institute of Pharmaceutical and Biomedical Science (IPBS), Johannes Gutenberg University Mainz, Mainz 55128, Germany.
  • Johannes Miedema
    Institute of Human Genetics, University Medical Center Mainz, Mainz 55128, Germany.
  • Stefan Pastore
    Institute of Pharmaceutical and Biomedical Science (IPBS), Johannes Gutenberg University Mainz, Mainz 55128, Germany.
  • Lioba Lehmann
    Institute of Human Genetics, University Medical Center Mainz, Mainz 55128, Germany.
  • Anna Wierczeiko
    Institute for Human Genetics, University Medical Center, Johannes Gutenberg University, 55131 Mainz, Germany.
  • Johannes Friedrich
    Computational and Biological Learning Laboratory, Department of Engineering, University of Cambridge, Cambridge CB2 1PZ, United Kingdom, and j.friedrich@columbia.edu.
  • Lukas Walz
    Institute of Pharmaceutical and Biomedical Science (IPBS), Johannes Gutenberg University Mainz, Mainz 55128, Germany.
  • Marko Jörg
    Institute of Pharmaceutical and Biomedical Science (IPBS), Johannes Gutenberg University Mainz, Mainz 55128, Germany.
  • Tamer Butto
    Institute of Pharmaceutical and Biomedical Science (IPBS), Johannes Gutenberg University Mainz, Mainz 55128, Germany.
  • Kristina Friedland
    Institute of Pharmaceutical and Biomedical Science (IPBS), Johannes Gutenberg University Mainz, Mainz 55128, Germany.
  • Mark Helm
    Institute of Pharmacy and Biochemistry, Johannes Gutenberg University Mainz, Mainz, Germany.
  • Susanne Gerber
    Institute of Human Genetics, University Medical Center, Mainz, Germany. sugerber@uni-mainz.de.