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 15 of 15 for “"mutational signature"”.
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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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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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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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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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Exploring mutational signatures in human cancers using human cell line models
… of cancer research for a long time, passenger mutational signatures – the imprints of DNA damage and DNA repair processes that have been operative during tumourigenesis – are also biologically informative. Since the inception of the field, many mutational signatures have been uncovered from the …
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The pathological and genomic impact of CTCF depletion in mammalian model systems
… whole genome sequencing, the highly reproducible mutational signature caused by DEN exposure was characterised, revealing that Braf(V637E), orthologous to BRAF(V600E) in humans, was the predominant oncogenic driver in these liver tumours. Taken together, while Ctcf loss is partially …
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Factors Influencing the Somatic Mutational Landscape of Ageing Squamous Epithelium
… radiation (UV) but, in Singapore, age-related signatures predominate. Mutations in TP53 are more strongly selected in epidermis of the UK, whilst those in NOTCH1 and NOTCH2 are preferentially selected in Singapore, reflecting differences in the level of competition within the tissue. A survey …
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An Investigation of Mutational Signatures in the Evolution of Oesophageal adenocarcinoma
An Investigation of Mutational Signatures in the Evolution of Oesophageal adenocarcinoma Sujath Abbas Oesophageal adenocarcinoma (OAC) remains a public health challenge with dismal survival rates and increasing incidence. This PhD study aimed to investigate how mutational processes act across …
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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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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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Investigating the regulation of APOBEC mutagenesis in cancer
… harbour recurrent patterns of mutation, known as mutational signatures. One common mutational signature, known as the APOBEC signature, is found in over 70% of cancer types. The APOBEC signature is thought to be mediated by the activity of the APOBEC enzyme family. However, the underlying cause of …
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Targeted sequencing : single cells and single strand breaks
… outcomes. We intentionally create a unique mutational signature at the SSB that is a fingerprint for this specific type of DNA damage when the locus is sequenced. Taken as a whole, we introduce two novel strategies to further understand cell function through studying rare cells in single …
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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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The impact of cytotoxic chemotherapy on somatic mutation in normal human cells
… mutagenesis. Patterns of mutations or ‘mutational signatures’ associated with chemotherapy have been seen in patient tumours, in cells exposed to drugs *in vitro*, and in some normal tissue samples from cancer patients. However, a comprehensive study of the impact of chemotherapy on the …
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Resolving the evolution of Oesophageal Adenocarcinoma using spatial and temporal sampling
… using PyClone and tree building by CloneEvol. Mutational signatures were identified using deconstructSigs. The gene panel ctDNA analysis included 245 double-spun plasma samples and 78 peripheral blood samples from 97 patients. The samples were prepared using the Roche expanded Avenio ctDNA …