Dissertations and Theses (Open Access)
Author ORCID Identifier
0000-0002-3733-5192
Date of Graduation
8-2026
Document Type
Dissertation (PhD)
Program Affiliation
Quantitative Sciences
Degree Name
Doctor of Philosophy (PhD)
Advisor/Committee Chair
Nicholas Navin
Committee Member
Chen Ken
Committee Member
Guillermina Lozano
Committee Member
Scott Kopetz
Committee Member
Ruoyan Li
Abstract
This dissertation deciphers somatic evolution and metastatic dissemination through single-cell copy number profiling by integrating experimental and computational advances. First, to de-fine the baseline of copy number mosaicism in healthy tissues, I profiled 83,206 epithelial cells from normal breast tissues of 49 healthy women using single-cell DNA sequencing and analyzed matched single-cell DNA&ATAC co-assays from 19 women, showing that all women harbor rare aneuploid epithelial cells (median 3.19%) that increase with age and most aneuploid cells undergo clonal expansion (median 82.22%). The recurrent CNA events, including 1q gain and 10q/16q/22q losses, overlap with alterations seen in invasive breast cancers while belong mainly to luminal lin-eages in histologically normal ductal and lobular structures. Second, I developed CopyKit, a scalable end-to-end framework for single-cell DNA copy number analysis, with a method to infer absolute ploidy at single-cell resolution. Applying these methods to 11,845 cells from primary tumors and matched metastases resolved clonal substructure, reconstructed metastatic lineages, identified primary-tumor subclones that seeded distant metastasis, and revealed both spatial in-termixing and regional segregation of subclones in liver metastases. Together, these results show that high-throughput single-cell copy number profiling, coupled with scalable and robust compu-tational modeling, can resolve phylogenetic evolution from normal tissue mosaicism to malignant evolution and provide a quantitative framework for studying tumor initiation, progression and metastasis.
Recommended Citation
Wang, Junke, "Deciphering Somatic Evolution and Metastasis Through Single-Cell Copy Number Profiling" (2026). Dissertations and Theses (Open Access). 1557.
https://digitalcommons.library.tmc.edu/utgsbs_dissertations/1557
Keywords
single cell genomics, cancer genomics, cancer evolution, copy number alteration, somatic mosaicism, computational biology