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

Hdl Handle:
http://hdl.handle.net/10147/336268
Title:
Computational approach for calculating the probability of eukaryotic translation initiation from ribo-seq data that takes into account leaky scanning
Authors:
Michel, Audrey M; Andreev, Dmitry E; Baranov, Pavel V
Citation:
Michel, M., Andreev, E., Baranov, V., 2014. Computational approach for calculating the probability of eukaryotic translation initiation from ribo-seq data that takes into account leaky scanning. BMC Bioinformatics, 2014. 15 (1) pp 380
Issue Date:
21-Nov-2014
URI:
http://dx.doi.org/10.1186/s12859-014-0380-4; http://hdl.handle.net/10147/336268
Abstract:
Abstract Background 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 conditions.
Language:
en
Keywords:
GENETICS; SCREENING

Full metadata record

DC FieldValue Language
dc.contributor.authorMichel, Audrey Men_GB
dc.contributor.authorAndreev, Dmitry Een_GB
dc.contributor.authorBaranov, Pavel Ven_GB
dc.date.accessioned2014-11-27T12:52:11Z-
dc.date.available2014-11-27T12:52:11Z-
dc.date.issued2014-11-21-
dc.identifier.citationMichel, M., Andreev, E., Baranov, V., 2014. Computational approach for calculating the probability of eukaryotic translation initiation from ribo-seq data that takes into account leaky scanning. BMC Bioinformatics, 2014. 15 (1) pp 380en_GB
dc.identifier.urihttp://dx.doi.org/10.1186/s12859-014-0380-4-
dc.identifier.urihttp://hdl.handle.net/10147/336268-
dc.description.abstractAbstract Background 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 conditions.-
dc.language.isoenen
dc.subjectGENETICSen_GB
dc.subjectSCREENINGen_GB
dc.titleComputational approach for calculating the probability of eukaryotic translation initiation from ribo-seq data that takes into account leaky scanningen_GB
dc.language.rfc3066en-
dc.rights.holderAudrey M Michel et al.; licensee BioMed Central Ltd.-
dc.description.statusPeer Reviewed-
dc.date.updated2014-11-26T08:04:36Z-
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