Somatic mutation analysis for the study of clonal evolution in cancer
department or school: Science, Faculty of
department or school: Computer Science, Department of
data provider: DSpace
degree campus: UBCV
creator: Dorri, Fatemeh
issued: 2022-03-31T07:00:00Z
issued: 2020
related degree: Doctor of Philosophy - PhD
degree grantor: University of British Columbia
description: Next generation sequencing (NGS) technology provides researchers an opportunity to study cancer genomes at different resolutions. In particular, detection and interpretation of the smallest somatic changes of the genome (single nucleotide variants) are now tractable at scale. However, significant challenges in the analysis of both bulk tumour and single cell sequencing methods remain to fully exploit the advance in technology development. Two emerging areas of applying sequencing technology to better ascertain properties of cancer evolution are (i) sequencing multiple tumour biopsies from the same patient, and (ii) single cell genome sequencing. Both of these advances represent computational challenges that I address through development of novel methods in this thesis. The first proposed method (Chapter 2) incorporates prior clonal information to improve the accuracy of detecting SNVs across the genome of multiple bulk tumour samples. The second proposed method (Chapter 3) is a statistical model that exploits the underlying phylogeny of individually sequenced cells to detect SNVs in every individual cell. The latter method identifies clone specific SNVs without the requirement of deconvolving the results from bulk sequencing data. The resultant accurate detection of SNVs (Chapter 4) helps enhance insight on the evolutionary process of tumours and genetic pathways. Together, the methods provide a toolbox for comprehensive profiling of SNVs for the study of tumour dynamics.
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/74261
note: Somatic mutation analysis for the study of clonal evolutionin cancerbyFatemeh DorriMSc, University of Waterloo, 2012A THESIS SUBMITTED IN PARTIAL FULFILLMENTOF THE REQUIREMENTS FOR THE DEGREE OFDoctor of PhilosophyinTHE FACULTY OF GRADUATE AND POSTDOCTORALSTUDIES(Computer Science)The University of British Columbia(Vancouver)April 2020c© Fatemeh Dorri, 2020The following individuals certify that they have read, and recommend to the Fac-ulty of Graduate and Postdoctoral Studies for acceptance, the thesis entitled:Somatic mutation analysis for the study of clonal evolution in cancersubmitted by Fatemeh Dorri in partial fulfillment of the requirements for the de-gree of Doctor of Philosophy in Computer Science.Examining Committee:Dr. Sohrab Shah, Department of Pathology and Laboratory Medicine, Departmentof Molecular OncologyCo-SupervisorDr. Anne Condon, Department of Computer ScienceCo-SupervisorDr. Alexandre Bouchard-Côté, Department of StatisticsSupervisory Committee MemberDr. Gabriela V. Cohen Freue, Department of StatisticsUniversity ExaminerDr. Sara Mostafavi, Department of StatisticsUniversity ExamineriiAbstractNext generation sequencing (NGS) technology provides researchers an opportu-nity to study cancer genomes at different resolutions. In particular, detection andinterpretation of the smallest somatic changes of the genome (single nucleotidevariants) are now tractable at scale. However, significant challenges in the analysisof both bulk tumour and single cell sequencing methods remain to fully exploitthe advance in technology development. Two emerging areas of applying sequenc-ing technology to better ascertain properties of cancer evolution are (i) sequenc-ing multiple tumour biopsies from the same patient, and (ii) single cell genomesequencing. Both of these advances represent computational challenges that I ad-dress through development of novel methods in this thesis. The first proposedmethod (Chapter 2) incorporates prior clonal information to improve the …
has type: Thesis/Dissertation
date issued: 2020-05
is shown at: 10.14288/1.0390286
language: eng
degree discipline: Computer Science
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-NoDerivatives 4.0 International
rights URI: http://creativecommons.org/licenses/by-nc-nd/4.0/
scholar level: Graduate
type: Text
identifier URI: http://hdl.handle.net/2429/74261