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 16 of 16 for “"Mutation burden"”.
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Assessing Tumor Mutation Burden and Correlation With Anti-PD-1/L1 Therapy Benefit and Prognosis
… of patients across all cancer types. Tumor mutation burden (TMB) is postulated to be a generic determinant of ICI dependent-tumor rejection. Here, we clarify the association between TMB and survival outcomes among microsatellite-stable cancers in a real-world clinicogenomic cohort including …
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Clonal dynamics of haematopoiesis across the human lifespan
… perturbations on haematopoietic stem cell mutation burden and clonal dynamics. To answer the ageing question, I have sequenced 3579 genomes from single-cell-derived colonies of haematopoietic stem cell/multipotent progenitors (HSC/MPPs) from 10 haematologically normal subjects aged 0-81 …
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Factors Influencing the Somatic Mutational Landscape of Ageing Squamous Epithelium
… influence of cancer risk factors on the somatic mutations present in normal aged skin and oesophageal epithelium using a range of sequencing methods. I find sun-exposed facial skin from donors of the UK to have a 4-fold increased mutation burden and 10-fold increase in copy number aberrant clones …
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Somatic evolution in healthy and chronically inflamed colon and skin
… that the IBD-colon is characterized by a higher mutation burden and larger clonal expansions than the healthy colon. I also show that muta- tions in immune-related genes, including PIGR, ZC3H12A and genes in the interleuking 17 and toll-like receptor pathways, are under positive selection in the …
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INTEGRATED SINGLE-CELL MUTATION, GENE EXPRESSION AND ISOFORM ANALYSIS TO DECONVOLVE ACUTE MYELOID LEUKEMIA HETEROGENEITY
… heterogeneity, including genetic (DNA mutations), phenotypic (transcriptional patterns) and ecological (interactions with host immune-cells) diversity. Emerging evidence suggest that intra-tumor heterogeneity impacts directly on leukemogenesis, disease prognosis and …
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A B-cell or a key player?: The role of the humoral immune response in melanoma, highlighting the importance of method development
… between these data and gene expression, tumour mutation burden, MHC types and protein subcellular location were explored in relation to potential drivers of autoantibody production. The reactivity profiles of patients with metastasised melanoma prior to receiving treatment were then compared to …
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A comprehensive survey of somatic mutation landscapes in normal human cells
Somatic mutations play an important role in cancer development and may contribute to the ageing process. These genetic alterations can be driven by endogenous factors such as errors during DNA replication, defects in DNA repair mechanisms, and oxidative damage, or by exogenous mutagens such as …
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Applications of mitochondrial gene therapy
… as clinical pathologies. Along with genetic mutations in nuclear encoded mitochondrial genes, these pathologies form a group of genetic disorders referred to as mitochondrial diseases. Engineered mitochondrially targeted zinc finger nucleases (mtZFNs) have been successfully used to …
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Multi-omic characterisation of Barrett’s oesophagus reveals a molecular continuum in the progression to oesophageal adenocarcinoma
… BE is highly heterogeneous with regards to mutational load, copy-number aberrations (CNAs) and structural variants (SVs). Mutational signatures are laid down early and persist regardless of progression status. Hence, Cosmic signature 17 (T:A>G:C in a CTT context), the hallmark of OAC, is …
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Integrative analysis of the metastatic neuroblastoma transcriptome
… basis of the disease and revealed a low somatic mutation burden. In order to identify novel therapeutic targets and better understand the biology of high-risk NBLs, I investigated whole transcriptome profiles of two cohorts of metastatic NBLs using RNA sequencing. First, I studied changes in …
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Somatic Mutations in Ageing and Degenerative Disease
… the first division of the zygote, somatic mutations begin to accumulate in all human cells. Daughter cells become increasingly mutated leading to mosaic tissues, composed of genetically heterogeneous clonal units. In recent years, large scale sequencing efforts have begun to characterise …
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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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Host somatic variation between women living with HIV with cervical intraepitheial lesions (CIN3) and their HIV negative counterparts
… HIV-positive women having a significantly higher burden of pathogenic variants (31%) compared to 15% among the HIV-negative (p=0.0406). Identified mutations included stop-gain, missense, synonymous, and intron variants. The genes TP53 and PIK3CA had more stop-gain variants among HIV-positive women …
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Elucidating TRPA1 Ion Channel Aberrations in Oesophageal Adenocarcinoma.
… variations and is characterised by high mutation burden. Although recurrent mutations are observed in only few genes, we have identified TRPA1 (Transient Receptor Potential Ankyrin 1) as a novel driver gene in OAC with recurrent mutations in a sequenced cohort of 551 OAC patients. TRPA1 …
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Genetic diversity and population structure within Botswana: association with HIV-1 infection
… strategies against HIV-1. Despite the high burden of HIV-1 in Botswana, the population of Botswana is significantly underrepresentation in genomics studies of HIV-1. Furthermore, the bulk of previous genomics studies evaluated common human genetic variations, however, there is increasing …
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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 …