Introduction

Ribosome profiling via high-throughput sequencing (ribo-seq) is a promising new technique for characterizing the occupancy of ribosomes on messenger RNA (mRNA) at base-pair resolution. The ribosome is responsible for translating mRNA into proteins, so information about its occupancy offers a detailed view of ribosome density and position which could be used to discover new translated open reading frames (ORFs), among other things. In this work, we propose Rp-Bp, an unsupervised Bayesian approach to predict translated ORFs from ribosome profiles. We use state-of-the-art Markov chain Monte Carlo techniques to estimate posterior distributions of the likelihood of translation of each ORF. Hence, an important feature of Rp-Bp is its ability to incorporate and propagate uncertainty in the prediction process. A second novel contribution is automatic Bayesian selection of read lengths and ribosome P-site offsets (BPPS). We empirically demonstrate that our read length selection technique modestly improves sensitivity by identifying more canonical and non-canonical ORFs. Proteomics- and quantitative translation initiation sequencing-based validation verifies the high quality of all of the predictions. Experimental comparison shows that Rp-Bp results in more peptide identifications and proteomics-validated ORF predictions compared to another recent tool for translation prediction.

Publications

  1. Bayesian prediction of RNA translation from ribosome profiling.
    Cite this
    Malone B, Atanassov I, Aeschimann F, Li X, Großhans H, Dieterich C, 2017-04-01 - Nucleic acids research

Credits

  1. Brandon Malone
    Developer

    DZHK (German Centre for Cardiovascular Research), Partner site Heidelberg/Mannheim, Germany

  2. Ilian Atanassov
    Developer

    Max Plank Institute for the Biology of Ageing, 50931 Köln, Germany

  3. Florian Aeschimann
    Developer

    Faculty of Science, University of Basel, Switzerland

  4. Xinping Li
    Developer

    Max Plank Institute for the Biology of Ageing, 50931 Köln, Germany

  5. Helge Großhans
    Developer

    Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland

  6. Christoph Dieterich
    Investigator

    DZHK (German Centre for Cardiovascular Research), Partner site Heidelberg/Mannheim, Germany

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Summary
AccessionBT006494
Tool TypeApplication
Category
PlatformsLinux/Unix
Technologies
User InterfaceTerminal Command Line
Download Count0
Country/RegionGermany
Submitted ByChristoph Dieterich