Visualising ribosome profiling and using it for reading frame detection and exploration of eukaryotic translation initiation

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dc.contributor.advisor Atkins, John F. en
dc.contributor.advisor Baranov, Pavel V. en
dc.contributor.author Mannion Michel, Audrey
dc.date.accessioned 2014-06-13T10:20:30Z
dc.date.issued 2013
dc.date.submitted 2014
dc.identifier.citation Mannion Michel, A. 2013. Visualising ribosome profiling and using it for reading frame detection and exploration of eukaryotic translation initiation. PhD Thesis, University College Cork. en
dc.identifier.endpage 254
dc.identifier.uri http://hdl.handle.net/10468/1575
dc.description.abstract Ribosome profiling (ribo-seq) is a recently developed technique that provides genomewide information on protein synthesis (GWIPS) in vivo. The high resolution of ribo-seq is one of the exciting properties of this technique. In Chapter 2, I present a computational method that utilises the sub-codon precision and triplet periodicity of ribosome profiling data to detect transitions in the translated reading frame. Application of this method to ribosome profiling data generated for human HeLa cells allowed us to detect several human genes where the same genomic segment is translated in more than one reading frame. Since the initial publication of the ribosome profiling technique in 2009, there has been a proliferation of studies that have used the technique to explore various questions with respect to translation. A review of the many uses and adaptations of the technique is provided in Chapter 1. Indeed, owing to the increasing popularity of the technique and the growing number of published ribosome profiling datasets, we have developed GWIPS-viz (http://gwips.ucc.ie), a ribo-seq dedicated genome browser. Details on the development of the browser and its usage are provided in Chapter 3. One of the surprising findings of ribosome profiling of initiating ribosomes carried out in 3 independent studies, was the widespread use of non-AUG codons as translation initiation start sites in mammals. Although initiation at non-AUG codons in mammals has been documented for some time, the extent of non-AUG initiation reported by these ribo-seq studies was unexpected. In Chapter 4, I present an approach for estimating the strength of initiating codons based on the leaky scanning model of translation initiation. Application of this approach to ribo-seq data illustrates that initiation at non-AUG codons is inefficient compared to initiation at AUG codons. In addition, our approach provides a probability of initiation score for each start site that allows its strength of initiation to be evaluated. en
dc.description.sponsorship Irish Research Council for Science Engineering and Technology (EMBARK Initiative) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher University College Cork en
dc.relation.uri http://gwips.ucc.ie
dc.rights © 2013, Audrey Mannion Michel en
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/3.0/ en
dc.subject Ribosome profiling en
dc.subject Dual coding en
dc.subject Translation initiation en
dc.subject Ribosome profiling visualisation en
dc.subject GWIPS-viz en
dc.subject Genome-wide information on protein synthesis (GWIPS) en
dc.title Visualising ribosome profiling and using it for reading frame detection and exploration of eukaryotic translation initiation en
dc.type Doctoral thesis en
dc.type.qualificationlevel Doctoral en
dc.type.qualificationname PhD (Science) en
dc.internal.availability Full text available en
dc.check.info Please note that Chapter 4 (pp.63-75) and Chapter 5 (pp.91-254) are unavailable due to a restriction requested by the author. en
dc.check.date 10000-01-01
dc.description.version Accepted Version
dc.contributor.funder Irish Research Council for Science Engineering and Technology en
dc.description.status Not peer reviewed en
dc.internal.school Biochemistry en
dc.check.reason This thesis is due for publication or the author is actively seeking to publish this material en
dc.check.opt-out Not applicable en
dc.thesis.opt-out false
dc.check.chapterOfThesis Chapters of thesis - 4,5
dc.check.embargoformat Both hard copy thesis and e-thesis en
ucc.workflow.supervisor j.atkins@ucc.ie
dc.internal.conferring Spring Conferring 2014 en


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