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

Jun SH, Toosi H, Mold J, Engblom C, Chen X, O'Flanagan C, Hagemann-Jensen M, Sandberg R, Aparicio S, Hartman J, Roth A, Lagergren J

Nat Commun 14 (1) 982 [2023-02-22; online 2023-02-22]

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.

Camilla Engblom

SciLifeLab Fellow

PubMed 36813776

DOI 10.1038/s41467-023-36202-y

Crossref 10.1038/s41467-023-36202-y

pmc: PMC9946941
pii: 10.1038/s41467-023-36202-y

Publications 9.5.0