A comparative genomic framework for the in silico design and assessment of molecular typing methods using whole-genome sequence data with application to Listeria monocytogenes

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Kruczkiewicz, Peter
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Lethbridge, Alta. : University of Lethbridge, Dept. of Biological Sciences, c2013
Although increased genome sequencing e orts have increased our understanding of genomic variability within many bacterial species, there has been limited application of this knowledge towards assessing current molecular typing methods and developing novel molecular typing methods. This thesis reports a novel in silico comparative genomic framework where the performance of typing methods is assessed on the basis of the discriminatory power of the method as well as the concordance of the method with a whole-genome phylogeny. Using this framework, we designed a comparative genomic ngerprinting (CGF) assay for Listeria monocytogenes through optimized molecular marker selection. In silico validation and assessment of the CGF assay against two other molecular typing methods for L. monocytogenes (multilocus sequence typing (MLST) and multiple virulence locus sequence typing (MVLST)) revealed that the CGF assay had better performance than these typing methods. Hence, optimized molecular marker selection can be used to produce highly discriminatory assays with high concordance to whole-genome phylogenies. The framework described in this thesis can be used to assess current molecular typing methods against whole-genome phylogenies and design the next generation of high-performance molecular typing methods from whole-genome sequence data.
xiii, 100 leaves : ill. ; 29 cm
Bacterial genomes -- Identification -- Computer simulation , Bacteria -- Identification -- Computer simulation , Gene mapping -- Computer simulation , Listeria monocytogenes -- Identification -- Technique , Dissertations, Academic