Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 29 for “"mutational processes"”.
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Mutational processes in normal human tissues
… of somatic mutations is shaped by numerous mutational processes, each generating a distinctive profile of mutations, called a ‘mutational signature’. From mutational signatures, one can infer a history of operating mutational processes that have acted on the genome. Therefore, they can be a …
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Germline and somatic mutational processes across the Tree of Life
… control samples with characterised somatic mutational processes, along with a negative control sample to establish the limit of detection. The mutational spectra derived from the detected somatic mutations closely matched the expected profiles of the positive controls, supporting the …
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The origin and consequences of mutational processes in the human germline
Mutational processes in the germline tissue can generate heritable genetic variation and have the potential to shape disease risk as well as species evolution. In this dissertation, by leveraging data from multiple sources, I explored three mutational processes in the human germline, each having …
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Analysis of the impact on phylogenetic inference of non-reversible nucleotide substitution models
… reason to assume that the underlying biochemical mutational processes that cause substitutions are similarly symmetrical. Here, we evaluate the effect on phylogenetic inference in empirical viral and simulated data of incorporating non-reversibility into models of nucleotide substitution …
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Automatic Tumour Typing based on Patterns of Somatic Passenger Mutations
… regional mutation density and cancer type, and mutational processes and cancer type. Somatic point mutations accu- mulate in regions of closed chromatin, and so mutation density provides information about chromatin state, which in turn offers hints about the underlying cell type. As some …
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Somatic Mutations in Ageing and Degenerative Disease
… disease. To accurately characterise the mutational processes in normal tissues, we developed nanorate sequencing (NanoSeq), a duplex sequencing protocol with error rates of less than five errors per billion base pairs, allowing for the accurate identification of mutations in single DNA …
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Genomic aberrations as determinants of immune infiltrates in high grade serous ovarian carcinoma
… in high grade serous ovarian cancer (HGSOC), mutational processes by which tumours gain immunogenicity or develop immune evasion are yet to be identified. Mutational processes that play a key role in HGSOC tumourigenesis leave imprints of copy-number aberrations (CNA) in the patient’s genome. …
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Quantifying the pro- and antimutagenic roles of DNA damage and repair
… a range of diseases including cancer. Different mutational processes often leave behind characteristic patterns of mutations, so-called mutational signatures. Mutational signature analysis of tumours has gained a lot of attention recently, because it may reveal carcinogenic exposures and also …
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Somatic evolution in normal human endometrium
… insights into the tumour burdens and underlying mutational processes, sub-clonal diversification and tumour heterogeneity. However, all cancers arise from cells that were once normal. Over time, they acquired certain mutations which increased their fitness, giving them a selective advantage over …
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Somatic evolution in human blood and colon
… evolution: blood for clonal dynamics; colon for mutational processes. Blood presents an opportunity to study normal human clonal dynamics, as clones mix spatially and longitudinal samples can be taken. We isolated 140 single haematopoietic stem and progenitor cells from a healthy 59 year-old and …
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Driver genes, mutational signatures and the timing of mutations in oesophageal adenocarcinoma
… of information regarding the mutations and mutational processes that drive OAC is likely contributing to this. However to understand the development of a cancer it is not enough to simply identify commonly mutated genes, rather it is also crucial to identify the timings at which these …
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Mapping the Genomic Context of Mutagenesis
… efforts have been undertaken to characterise mutational processes in terms of their genomic imprints. A particularly successful approach is matrix-based mutational signature analysis, which identifies prototypical mutation patterns by applying non-negative matrix factorisation to catalogues of …
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Compositional models for mutational signature analysis
… life, or even throughout tumour development. Mutational signatures were introduced as a proxy to quantify the number of mutations created by each mutational process. This thesis focuses on statistical methods for the analysis of such mutational signatures. Crucially, mutational signatures, in …
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Role of inherited DNA repair deficiencies in cancer susceptibility and evolution
… and genome stability. Deficiencies in these processes result in an accumulation of post-zygotic mutations with characteristic signatures. This genomic instability is associated with the heritability of multiple cancer syndromes. I explored the role of inherited DNA repair deficiencies in …
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Computational Discovery and Analysis of rDNA Sequence Heterogeneity in Yeast
… amongst units. Opposing these divergent mutational processes, unit sequences are homogenised through concerted evolutionary processes such as unequal sister chromatid exchange (USCE) and gene conversion (GC). In this study Perl software has been used to uncover rDNA sequence variation in …
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Following the LINEs (Long INterspersed Elements): human specific L1 elements and their orthologous loci in non-human primates
… variants that occurred as a result of common mutational processes in ancestral sequences, often including regions containing simple sequence repeats. Additional sequence variation included genomic deletions that occurred upon L1 insertion, as well as successive mobile element insertions that …
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A comprehensive survey of somatic mutation landscapes in normal human cells
… mutations over a lifetime involves multiple mutational processes, each with distinct mutation patterns, known as mutational signatures. Recent studies have shown that the somatic mutation burden varies between cell types, tissues, organs and individuals. However, due to technical limitations, …
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Measuring ongoing chromosomal instability in single-cell DNA sequencing data
… scUnique detects differences in the activity of mutational processes in cell lines derived from treatment naive and relapse tumour samples. By measuring chromosomal instability at the level of individual cells, we provide quantitative, scalable and whole-genome level information about the …
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Somatic mutagenesis in humans with deficient DNA repair
… selected to investigate the mutation burdens and mutational processes across different normal tissue types. Individuals with these syndromes have a known elevated risk of cancer which is thought to be underpinned by an increased somatic mutation rate. Chapter 3 summarises experiments that …
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Somatic Mutation in Cancer and Healthy Human Tissue
… how genetic mutations and evolutionary processes shape cancer initiation and progression. More recently, sequencing efforts have shifted towards normal human tissues to explore their somatic mutational landscapes in order to understand the processes before cancer initiation. Here, data …
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