Deep learning to decode sites of RNA translation in normal and cancerous tissues.

Journal: Nature communications
PMID:

Abstract

The biological process of RNA translation is fundamental to cellular life and has wide-ranging implications for human disease. Accurate delineation of RNA translation variation represents a significant challenge due to the complexity of the process and technical limitations. Here, we introduce RiboTIE, a transformer model-based approach designed to enhance the analysis of ribosome profiling data. Unlike existing methods, RiboTIE leverages raw ribosome profiling counts directly to robustly detect translated open reading frames (ORFs) with high precision and sensitivity, evaluated on a diverse set of datasets. We demonstrate that RiboTIE successfully recapitulates known findings and provides novel insights into the regulation of RNA translation in both normal brain and medulloblastoma cancer samples. Our results suggest that RiboTIE is a versatile tool that can significantly improve the accuracy and depth of Ribo-Seq data analysis, thereby advancing our understanding of protein synthesis and its implications in disease.

Authors

  • Jim Clauwaert
    Department of Data Analysis and Mathematical Modelling, Ghent University, Coupure Links 653, 9000 Gent, Belgium.
  • Zahra McVey
    Novo Nordisk Research Centre Oxford, Novo Nordisk Ltd, Oxford, UK.
  • Ramneek Gupta
    Department of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark.
  • Ian Yannuzzi
    Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Venkatesha Basrur
    Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
  • Alexey I Nesvizhskii
    Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA.
  • Gerben Menschaert
    BioBix, Department of Data Analysis and Mathematical Modelling, Ghent University, Coupure Links 653, 900, Gent, Belgium. Electronic address: gerben.menschaert@ugent.be.
  • John R Prensner
    Division of Pediatric Hematology/Oncology, Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA. prensner@umich.edu.