Single-cell phylogenies reveal changes in the evolutionary rate within cancer and healthy tissues
Open access
Date
2023-09-13Type
- Journal Article
ETH Bibliography
yes
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Abstract
Cell lineages accumulate somatic mutations during organismal development, potentially leading to pathological states. The rate of somatic evolution within a cell population can vary due to multiple factors, including selection, a change in the mutation rate, or differences in the microenvironment. Here, we developed a statistical test called the Poisson Tree (PT) test to detect varying evolutionary rates among cell lineages, leveraging the phylogenetic signal of single-cell DNA sequencing (scDNA-seq) data. We applied the PT test to 24 healthy and cancer samples, rejecting a constant evolutionary rate in 11 out of 15 cancer and five out of nine healthy scDNA-seq datasets. In six cancer datasets, we identified subclonal mutations in known driver genes that could explain the rate accelerations of particular cancer lineages. Our findings demonstrate the efficacy of scDNA-seq for studying somatic evolution and suggest that cell lineages often evolve at different rates within cancer and healthy tissues. Show more
Permanent link
https://doi.org/10.3929/ethz-b-000631625Publication status
publishedExternal links
Journal / series
Cell GenomicsVolume
Pages / Article No.
Publisher
Cell PressSubject
Somatic evolution; Single-cell DNA sequencing; Single-cell phylogenies; Evolutionary rate variation; Molecular clock; Cell lineageOrganisational unit
03790 - Beerenwinkel, Niko / Beerenwinkel, Niko
Funding
766030 - Computational ONcology TRaining Alliance (EC)
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ETH Bibliography
yes
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