Deciphering the heterogeneity and spatial architecture of tumors
Wu, Jiaqi
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https://hdl.handle.net/2142/108185
Description
Title
Deciphering the heterogeneity and spatial architecture of tumors
Author(s)
Wu, Jiaqi
Issue Date
2020-05-12
Director of Research (if dissertation) or Advisor (if thesis)
El-Kebir, Mohammed
Department of Study
Computer Science
Discipline
Computer Science
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
M.S.
Degree Level
Thesis
Keyword(s)
intra-tumor heterogeneity, cancer genomics, bioinformatics, genome analysis, spatial analytics, visualization
Abstract
Cancer is caused by the accumulation of somatic mutations that form distinct populations of cells, called clones. The resulting intra-tumor heterogeneity evolves temporally, as well as spatially, and is the main cause of relapse and resistance to treatment. With decreasing costs in DNA sequencing technology, rich cancer genomics datasets that effectively capture mutational signals in cancer have become available, allowing researchers to closely examine the underlying mechanisms that shape the tumor landscape. In this thesis, we explore the multi-faceted elements of intra-tumor heterogeneity via visualization, quantification, and detection. We begin by introducing ClonArch, a tool which interactively visualizes the evolutionary relationships and spatial distribution of clones in a single tumor mass. ClonArch fills the gap for visualizations that address spatial aspects of clonal architecture. We then adapt a cancer genomics pipeline to quantify intra-tumor heterogeneity in a porcine model, showing its potential impact on translational clinical studies. Finally, we attempt to detect negative selection in the cancer exome by performing a depletion analysis on neoantigens.
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