Computational approach for calculating the probability of eukaryotic translation initiation from ribo-seq data that takes into account leaky scanning

dc.contributor.authorMichel, Audrey M.
dc.contributor.authorAndreev, Dmitry E.
dc.contributor.authorBaranov, Pavel V.
dc.contributor.funderIrish Research Council for Science Engineering and Technologyen
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderWellcome Trust, United Kingdomen
dc.contributor.funderEuropean Molecular Biology Conferenceen
dc.date.accessioned2016-01-20T10:43:40Z
dc.date.available2016-01-20T10:43:40Z
dc.date.issued2014-11-21
dc.description.abstractBACKGROUND: Ribosome profiling (ribo-seq) provides experimental data on the density of elongating or initiating ribosomes at the whole transcriptome level that can be potentially used for estimating absolute levels of translation initiation at individual Translation Initiation Sites (TISs). These absolute levels depend on the mutual organisation of TISs within individual mRNAs. For example, according to the leaky scanning model of translation initiation in eukaryotes, a strong TIS downstream of another strong TIS is unlikely to be productive, since only a few scanning ribosomes would be able to reach the downstream TIS. In order to understand the dependence of translation initiation efficiency on the surrounding nucleotide context, it is important to estimate the strength of TISs independently of their mutual organisation, i.e. to estimate with what probability a ribosome would initiate at a particular TIS. RESULTS: We designed a simple computational approach for estimating the probabilities of ribosomes initiating at individual start codons using ribosome profiling data. The method is based on the widely accepted leaky scanning model of translation initiation in eukaryotes which postulates that scanning ribosomes may skip a start codon if the initiation context is unfavourable and continue on scanning. We tested our approach on three independent ribo-seq datasets obtained in mammalian cultured cells. CONCLUSIONS: Our results suggested that the method successfully discriminates between weak and strong TISs and that the majority of numerous non-AUG TISs reported recently are very weak. Therefore the high frequency of non-AUG TISs observed in ribosome profiling experiments is due to their proximity to mRNA 5′-ends rather than their strength. Detectable translation initiation at non-AUG codons downstream of AUG codons is comparatively infrequent. The leaky scanning method will be useful for the characterization of differences in start codon selection between tissues, developmental stages and in response to stress conditionsen
dc.description.sponsorshipScience Foundation Ireland (12/IA/1335); Wellcome Trust, United Kingdom (094423); Irish Research Council (postgraduate fellowship); European Molecular Biology Conference (EMBO travel fellowship)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleid380
dc.identifier.citationMICHEL, A. M., ANDREEV, D. E. & BARANOV, P. V. 2014. Computational approach for calculating the probability of eukaryotic translation initiation from ribo-seq data that takes into account leaky scanning. BMC Bioinformatics, 15:380, 1-10. http://dx.doi.org/10.1186/s12859-014-0380-4en
dc.identifier.doi10.1186/s12859-014-0380-4
dc.identifier.endpage10en
dc.identifier.issn1471-2105
dc.identifier.journaltitleBMC Bioinformaticsen
dc.identifier.startpage1en
dc.identifier.urihttps://hdl.handle.net/10468/2200
dc.identifier.volume15en
dc.language.isoenen
dc.publisherBiomed Central Ltd.en
dc.rights© 2014 Michel et al.; licensee BioMed Central Ltd., 2014. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectLeaky scanningen
dc.subjectNon-AUG initiationen
dc.subjectRibosome profilingen
dc.subjectTranslation initiationen
dc.subject5′ leaderen
dc.subject5′ UTR TISsen
dc.subjectKozak contexten
dc.subjectuORFen
dc.subjectOpen reading frameen
dc.subjectMammalian cellsen
dc.subjectNucleotide resolutionen
dc.subjectProtein synthesisen
dc.subjectRibosomesen
dc.subjectSequencesen
dc.subjectReinitiationen
dc.subjectExtensionsen
dc.subjectArtificial intelligenceen
dc.subjectComputational methodsen
dc.subjectMacromoleculesen
dc.subjectMammalsen
dc.subjectProbabilityen
dc.subjectScanningen
dc.subjectEukaryotaen
dc.titleComputational approach for calculating the probability of eukaryotic translation initiation from ribo-seq data that takes into account leaky scanningen
dc.typeArticle (peer-reviewed)en
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