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Nat Methods. 2018 May;15(5):363-366. doi: 10.1038/nmeth.4631. Epub 2018 Mar 12.

Improved Ribo-seq enables identification of cryptic translation events.

Author information

1
Institute for Informatics, Ludwig-Maximilians-Universität München, München, Germany.
2
Institute for Virology and Immunobiology, Julius-Maximilians-Universität Würzburg, Würzburg, Germany.
3
Institute of Virology, Medical Center, University of Freiburg, Freiburg, Germany.
4
Faculty of Medicine, University of Freiburg, Freiburg, Germany.
5
Innovative Medicines & Early Development, AstraZeneca UK Ltd, Cambridge, UK.
6
Interfaculty Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany.
7
Immatics Biotechnologies GmbH, Tübingen, Germany.
8
Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.

Abstract

Ribosome profiling has been used to predict thousands of short open reading frames (sORFs) in eukaryotic cells, but it suffers from substantial levels of noise. PRICE (https://github.com/erhard-lab/price) is a computational method that models experimental noise to enable researchers to accurately resolve overlapping sORFs and noncanonical translation initiation. We experimentally validated translation using major histocompatibility complex class I (MHC I) peptidomics and observed that sORF-derived peptides efficiently enter the MHC I presentation pathway and thus constitute a substantial fraction of the antigen repertoire.

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