Electronic Thesis/Dissertation
 

Cell-level Mutational Signatures in Cancer

Open Access

Abstract of ThesisCell-level Mutational Signatures in Cancer Mutational signatures are the collection of operative mutational processes occurring in a cell. All cancer genomes carry somatic mutations, and these mutations can be caused by multiple mutational processes, each of which generates a characteristic signature unique to the mutation process. There is very infrequently a single mutagen or mutational event at play in a cancer cell, but rather there is an accumulation of damage in the nucleotide environment that is reflected in multiple identifiable signatures across a cell. While these signatures have been identified and studied largely at the genomic level, here we sought to utilize single-cell RNA sequencing (scRNA-seq) data where the alignments are split by cellular barcode before calling variants to study the composition of mutational signature profiles at the cell level. We highlight and utilize a novel methodology for uncovering single-cell exclusive single nucleotide variants (sceSNVs), and establish that the discovery of sceSNVs from individual cells can be applied to study mutations’ origin and evolution. We show that different cell types show different mutational signature compositions and highlight the differences in cellular heterogeneity across scRNA-seq samples, contributing to the identification and categorization of mutational signatures.

Author Language Date created Type of Work License
  • All rights reserved
Rights statement GW Unit Degree Advisor Committee Member(s) Persistent URL

Notice to Authors

If you are the author of this work and you have any questions about the information on this page, please use the Contact form to get in touch with us.

Thumbnail Title Date Uploaded Visibility Actions
Preview of Dillard_gwu_0075M_15987.pdf Dillard_gwu_0075M_15987.pdf 2022-10-04 Open Access
Preview of Suplementary_File_1.pptx Suplementary_File_1.pptx 2022-10-04 Open Access