Publications
Nature communicationsFeb 2023 |
14
(
1
),
982
DOI:
10.1038/s41467-023-36202-y

Reconstructing clonal tree for phylo-phenotypic characterization of cancer using single-cell transcriptomics

Jun, Seong-Hwan; Toosi, Hosein; Mold, Jeff; Engblom, Camilla; Chen, Xinsong; O'Flanagan, Ciara; Hagemann-Jensen, Michael; Sandberg, Rickard; Aparicio, Samuel; Hartman, Johan; Roth, Andrew; Lagergren, Jens
Product Used
NGS
Abstract
Functional characterization of the cancer clones can shed light on the evolutionary mechanisms driving cancer's proliferation and relapse mechanisms. Single-cell RNA sequencing data provide grounds for understanding the functional state of cancer as a whole; however, much research remains to identify and reconstruct clonal relationships toward characterizing the changes in functions of individual clones. We present PhylEx that integrates bulk genomics data with co-occurrences of mutations from single-cell RNA sequencing data to reconstruct high-fidelity clonal trees. We evaluate PhylEx on synthetic and well-characterized high-grade serous ovarian cancer cell line datasets. PhylEx outperforms the state-of-the-art methods both when comparing capacity for clonal tree reconstruction and for identifying clones. We analyze high-grade serous ovarian cancer and breast cancer data to show that PhylEx exploits clonal expression profiles beyond what is possible with expression-based clustering methods and clear the way for accurate inference of clonal trees and robust phylo-phenotypic analysis of cancer.
Product Used
NGS

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