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 60 for “"Driver mutations"”.
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Pan-Cancer Analysis of Non-Coding Driver Mutations
… are caused by genomic alterations known as drivers. As drivers have broad applications in precision oncology, their discovery has become one of the central motivations for cancer genomics. At present, the majority of drivers have been found in the ~2% protein-coding regions. Despite an …
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Transcription Factor-Centric Approaches to Identify Regulatory Driver Mutations in Cancer
<p>Most previous efforts to identify cancer driver mutations have focused on protein-coding genes. In recent years, the decreasing costs of DNA sequencing have enabled whole-genome sequencing (WGS) studies of thousands of tumor samples, making it possible to systematically survey non-coding regions …
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Computational Identification of Noncoding Driver Mutations Based On Impact On Rna Processing
<p>Despite the prevalence of mutations in the noncoding regions of the DNA, their effects on cancer development remain largely uninvestigated. This is especially evident when compared to coding mutations, which have been relatively well-studied and, in certain cases, been identified as driver …
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Integrated Machine Learning and Bioinformatics Approaches for Prediction of Cancer-Driving Gene Mutations
<p>Cancer arises from the accumulation of somatic mutations and genetic alterations in cell division checkpoints and apoptosis, this often leads to abnormal tumor proliferation. Proper classification of cancer-linked driver mutations will considerably help our understanding of the molecular …
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Evolution of the genome in myeloproliferative neoplasms and the methylome in blood
… remarkable insights into the rates that mutations are acquired throughout life, mutations that drive disease and the growth rates of clones that acquire driver mutations. Such metrics for DNA methylation, another heritable marker, are less well understood. In this thesis, I use two NGS …
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Clonal dynamics of haematopoiesis across the human lifespan
… aged 0-81 years. HSC/MPPs accumulated 17 somatic mutations/year after birth with no increased rate of mutation accumulation in the elderly. HSC/MPP telomere length declined by 30 bp/yr. To interrogate changes in HSC population structure with age, I used the pattern of unique and shared mutations …
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Defining the Epigenetic Evolutionary Dynamics that Precede Acute Myeloid Leukaemia
… are shaped by the acquisition of somatic driver mutations. Acute Myeloid Leukaemia (AML) is a good model system with which to address these questions. As well as the ease of sampling blood, mutations in epigenetic modifiers are some of the earliest and most common driver events in AML. In …
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Determinants of clinical phenotype in myeloproliferative neoplasms
… neoplasms, comprehensively annotating driver mutations and copy-number changes or copy. We developed a genomic classification for myeloproliferative neoplasms and multistage prognostic models for predicting outcomes in individual patients. Classification and prognostic models were …
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Identifying unique cell states in early liver oncogenesis with transcription coupled repair
… arise in tissues with a high number of genetic mutations which drive cell growth aberrantly. These mutations appear to precede tumour initiation, as DNA sequencing has shown that cancer driver mutations can be found in otherwise-healthy tissues at high levels. Though an increase in mutational …
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Role of ETV5 Mutations in B Cell Acute Lymphoblastic Leukemia
… (B-ALL) develops through the acquisition of driver mutations that impair cell differentiation and promote proliferation. In human B-ALL, mutations in E26 transformation-specific (ETS) transcription factors are commonly reported. Our laboratory studies a mouse model of B-ALL in which leukemia …
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The Intra-Tumour Heterogeneity Landscape of Human Cancers
Tumours accumulate many somatic mutations in their lifetime. Some of these mutations, drivers, convey a selective advantage and can induce clonal expansions. Incomplete clonal expansions give rise to intra-tumour heterogeneity. Somatic mutations can be measured through massively parallel …
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Computational Inferences of Mutations Driving Mesenchymal Differentiation in Glioblastoma
… systems biology methods designed to parse driver mutations from high- throughput array data derived from human patients. The analysis of vast amounts of genomic and genetic data in the context of complex human genetic diseases such as Glioblastoma is a daunting task. Mutations exist by the …
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Somatic evolution in normal human endometrium
… enabled identification and characterisation of driver mutations, provided 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 …
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Pan-cancer study of transcriptional responses to oncogenic somatic mutations
Cancer cells typically carry acquired somatic mutations in key cancer driver genes, which can be identified on the basis of recurrence in cancer cohorts. Such mutations may cause aberrant protein activity and altered gene expression in the nucleus, driving the cell toward a cancerous phenotype. …
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Accurate Mutation Annotation and Functional Prediction Enhance The Applicability of -Omics Data In Precision Medicine
… framework to precisely identify hotspot mutations and investigate their functional impact on tumorigenesis and drug therapeutic response using large-scale -omics data. I have proposed a statistical model, which utilizes characteristics of genomic data to nominate 702 cancer type-specific …
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Orthogonal Comparison of Nuclear and Mitochondrial Clonal Architectures in Hematologic Malignancies
… malignancy characterized by accumulation of mutations that disrupt hematopoietic differentiation and promote clonal expansion. Understanding how these mutations arise and evolve is essential for improving diagnosis, prognosis, and treatment stratification. Current methods are limited by …
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Trees and Forests: Data Science and Machine Learning Approaches to Characterise Clonal Haematopoiesis
… haematopoietic stem cell (HSC) driven by somatic mutations in leukaemia-associated genes, is a common age-related phenomenon that affects more than 20% of adults aged over 70 years. As the shared precursor of most myeloid neoplasms (MN), timely detection of CH can offer an opportunity for cancer …
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Tissue adaptations to colitis influence neoplastic risk through clonal interaction
… for tissue regeneration. Introduction of cancer-driver mutations in *Trp53* and *Kras* in a *Muc2<sup>KO</sup>* background had limited impact on survival and pathology, which drew interesting parallels between tissue regenerative processes and cancer initiation. Such processes were explored in …
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Molecular evolution of biological sequences
… undergoing rapid adaptation acquire multiple mutations that are physically linked in the genome, so their fates are mutually dependent and selection only acts on these loci in their entirety. This aspect has been largely overlooked in the study of asexual or somatic evolution and plays a major …
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