RT Journal Article
SR Electronic
T1 A Phylogenetic Approach to Inferring the Order in Which Mutations Arise during Cancer Progression
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.05.06.081398
DO 10.1101/2020.05.06.081398
A1 Yuan Gao
A1 Jeff Gaither
A1 Julia Chifman
A1 Laura Kubatko
YR 2021
UL http://biorxiv.org/content/early/2021/12/15/2020.05.06.081398.abstract
AB Although the role of evolutionary process in cancer progression is widely accepted, increasing attention is being given to the evolutionary mechanisms that can lead to differences in clinical outcome. Recent studies suggest that the temporal order in which somatic mutations accumulate during cancer progression is important. Single-cell sequencing provides a unique opportunity to examine the mutation order during cancer progression. However, the errors associated with single-cell sequencing complicate this task. We propose a new method for inferring the order in which somatic mutations arise within a tumor using noisy single-cell sequencing data that incorporates the errors that arise from the data collection process. Using simulation, we show that our method outperforms existing methods for identifying mutation order in most cases, especially when the number of cells is large. Our method also provides a means to quantify the uncertainty in the inferred mutation order along a fixed phylogeny. We apply our method to empirical data from colorectal and prostate cancer patients.Competing Interest StatementThe authors have declared no competing interest.