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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
Nature communications, 02/2023, Letnik: 14, Številka: 1Journal Article
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.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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