Variation-aware algorithms for cancer genome analysis
type: CreativeWork
description: In this thesis, I explore variation-aware algorithms for analyzing cancer genomes. The scientific community has extensively catalogued millions of mutations present in cancer cells. This information is rarely used during read alignment and variant calling because of a lack of algorithms for doing so. Rediscovering these variants wastes significant computational time and negatively impacts the sensitivity of detection, motivating the development of new solutions. The variants in malignant cells can arise from a number of genetic and environmental sources. In the years after the Chernobyl nuclear disaster, thousands of individuals in areas where radionuclides were deposited developed thyroid cancer. The excess relative risk of thyroid cancer has been estimated to be between fifteen and thirty fold higher following $^{131}I$ exposure. In Chapter 2, I analyze more than 300 thyroid cancer cases from children and young adults exposed to ionizing radiation from increased levels of $^{131}I$ originating from Chernobyl. I characterize the mutational landscape of these tumors across the variant size spectrum and compare it to sporadic thyroid cancer cases. I investigate possible signs of radiation exposure in the genome, especially large balanced structural variants and small indels. In Chapter 3, I develop methods for working with structural variants in variation graphs. Variation graphs have been shown to reduce reference bias and improve alignment to variant sites, though previous work has primarily focused on variants less than fifty base pairs in size. I describe the tradeoffs of various representations of large variants in the graph. I then develop several methods for genotyping and calling large variants in graphs. I construct graphs of both germline and somatic variation and describe how to work with these structures. I develop a method for fast structural variant genotyping using graph mappings and show that this significantly outperforms standard structural variant …
abstract: In this thesis, I explore variation-aware algorithms for analyzing cancer genomes. The scientific community has extensively catalogued millions of mutations present in cancer cells. This information is rarely used during read alignment and variant calling because of a lack of algorithms for doing so. Rediscovering these variants wastes significant computational time and negatively impacts the sensitivity of detection, motivating the development of new solutions. The variants in malignant cells can arise from a number of genetic and environmental sources. In the years after the Chernobyl nuclear disaster, thousands of individuals in areas where radionuclides were deposited developed thyroid cancer. The excess relative risk of thyroid cancer has been estimated to be between fifteen and thirty fold higher following $^{131}I$ exposure. In Chapter 2, I analyze more than 300 thyroid cancer cases from children and young adults exposed to ionizing radiation from increased levels of $^{131}I$ originating from Chernobyl. I characterize the mutational landscape of these tumors across the variant size spectrum and compare it to sporadic thyroid cancer cases. I investigate possible signs of radiation exposure in the genome, especially large balanced structural variants and small indels. In Chapter 3, I develop methods for working with structural variants in variation graphs. Variation graphs have been shown to reduce reference bias and improve alignment to variant sites, though previous work has primarily focused on variants less than fifty base pairs in size. I describe the tradeoffs of various representations of large variants in the graph. I then develop several methods for genotyping and calling large variants in graphs. I construct graphs of both germline and somatic variation and describe how to work with these structures. I develop a method for fast structural variant genotyping using graph mappings and show that this significantly outperforms standard structural variant …
author: Dawson, Eric Thomas
language: en
keywords: Cancer, Genomics, Bioinformatics, Variation Graphs, Structural Variation, Ionizing Radiation, Chernobyl, Algorithms, Kmers, Human Papillomavirus, HPV, MinHash, Thyroid Cancer, Papillary Thyroid Carcinoma, Mutational Signatures, Indels, Genetics, Genetic Variation, Variant Calling, Genome Assembly, Somatic Variation
license: https://www.repository.cam.ac.uk/bitstreams/6005c3b2-1b6c-47b4-b1df-3b5535887667/download
license: https://creativecommons.org/licenses/by/4.0/
date published: 2020-05-16
date modified: 2026-07-22T22:23:56Z
provider: Cambridge University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cambridge

PropertyValue
property ID: DOI
value: 10.17863/CAM.51110