Comparative survey of the relative impact of mRNA features on local ribosome profiling read density

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dc.contributor.authorO'Connor, Patrick B. F.
dc.contributor.authorAndreev, Dmitry E.
dc.contributor.authorBaranov, Pavel V.
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderWellcome Trusten
dc.date.accessioned2016-11-16T16:32:20Z
dc.date.available2016-11-16T16:32:20Z
dc.date.issued2016-10-04
dc.description.abstractRibosome profiling (Ribo-seq), a promising technology for exploring ribosome decoding rates, is characterized by the presence of infrequent high peaks in ribosome footprint density and by long alignment gaps. Here, to reduce the impact of data heterogeneity we introduce a simple normalization method, Ribo-seq Unit Step Transformation (RUST). RUST is robust and outperforms other normalization techniques in the presence of heterogeneous noise. We illustrate how RUST can be used for identifying mRNA sequence features that affect ribosome footprint densities globally. We show that a few parameters extracted with RUST are sufficient for predicting experimental densities with high accuracy. Importantly the application of RUST to 30 publicly available Ribo-seq data sets revealed a substantial variation in sequence determinants of ribosome footprint frequencies, questioning the reliability of Ribo-seq as an accurate representation of local ribosome densities without prior quality control. This emphasizes our incomplete understanding of how protocol parameters affect ribosome footprint densities.en
dc.description.sponsorshipScience Foundation Ireland (12/IA/1335); Wellcome Trust (094423)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationO’Connor, P. B. F., Andreev, D. E. and P. V. Baranov (2016). ‘Comparative survey of the relative impact of mRNA features on local ribosome profiling read density’, Nature Communications, 7: 12915 (12 pp). doi: 10.1038/ncomms12915en
dc.identifier.doi10.1038/ncomms12915
dc.identifier.endpage12915-12en
dc.identifier.issn2041-1723
dc.identifier.journaltitleNature Communicationsen
dc.identifier.startpage12915-1en
dc.identifier.urihttps://hdl.handle.net/10468/3278
dc.identifier.volume7en
dc.language.isoenen
dc.publisherNature Publishing Groupen
dc.rights© The Authors 2016. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectRibosome profilingen
dc.subjectTranslational landscapeen
dc.subjectNucleotide resolutionen
dc.subjectProtein translationen
dc.subjectHuman genomeen
dc.subjectCodon biasen
dc.subjectIn-vivoen
dc.titleComparative survey of the relative impact of mRNA features on local ribosome profiling read densityen
dc.typeArticle (peer-reviewed)en
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