RT Journal Article
SR Electronic
T1 Theoretical Guarantees for Phylogeny Inference from Single-Cell Lineage Tracing
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.11.21.469464
DO 10.1101/2021.11.21.469464
A1 Robert Wang
A1 Richard Zhang
A1 Alex Khodaverdian
A1 Nir Yosef
YR 2021
UL http://biorxiv.org/content/early/2021/11/22/2021.11.21.469464.abstract
AB CRISPR-Cas9 lineage tracing technologies have emerged as a powerful tool for investigating development in single-cell contexts, but exact reconstruction of the underlying clonal relationships in experiment is plagued by data-related complications. These complications are functions of the experimental parameters in these systems, such as the Cas9 cutting rate, the diversity of indel outcomes, and the rate of missing data. In this paper, we develop two theoretically grounded algorithms for reconstruction of the underlying phylogenetic tree, as well as asymptotic bounds for the number of recording sites necessary for exact recapitulation of the ground truth phylogeny at high probability. In doing so, we explore the relationship between the problem difficulty and the experimental parameters, with implications for experimental design. Lastly, we provide simulations validating these bounds and showing the empirical performance of these algorithms. Overall, this work provides a first theoretical analysis of phylogenetic reconstruction in the CRISPR-Cas9 lineage tracing technology.Competing Interest StatementNY is an advisor and/or has equity in Cellarity, Celsius Therapeutics, and Rheos Medicine.