Accounting for errors in data improves timing in single-cell cancer evolution

Single-cell sequencing provides a new way to explore the evolutionary history of cells. Compared to traditional bulk sequencing, where a population of heterogeneous cells is pooled to form a single observation, single-cell sequencing isolates and amplifies genetic material from individual cells, the...

Full description

Saved in:
Bibliographic Details
Published inbioRxiv
Main Authors Chen, Kylie, Moravec, Jiri C, Gavryushkin, Alex, Welch, David, Drummond, Alexei J
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 11.05.2022
Subjects
Bayesian analysis
Cancer
Colorectal carcinoma
Divergence
Evolutionary genetics
Genetic diversity
Genotypes
Mathematical models
Molecular modelling
Mutation
Phylogeny
Online AccessGet full text

Cover

More Information
Summary:Single-cell sequencing provides a new way to explore the evolutionary history of cells. Compared to traditional bulk sequencing, where a population of heterogeneous cells is pooled to form a single observation, single-cell sequencing isolates and amplifies genetic material from individual cells, thereby preserving the information about the origin of the sequences. However, single-cell data is more error-prone than bulk sequencing data due to the limited genomic material available per cell. Here, we present error and mutation models for evolutionary inference of single-cell data within a mature and extensible Bayesian framework, BEAST2. Our framework enables integration with biologically informative models such as relaxed molecular clocks and population dynamic models. Our simulations show that modeling errors increase the accuracy of relative divergence times and substitution parameters. We reconstruct the phylogenetic history of a colorectal cancer patient and a healthy patient from single-cell DNA sequencing data. We find that the estimated times of terminal splitting events are shifted forward in time compared to models which ignore errors. We observed that not accounting for errors can overestimate the phylogenetic diversity in single-cell DNA sequencing data. We estimate that 30-50% of the apparent diversity can be attributed to error. Our work enables a full Bayesian approach capable of accounting for errors in the data within the integrative Bayesian software framework BEAST2. Competing Interest Statement The authors have declared no competing interest.
DOI:10.1101/2021.03.17.435906