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Theoretical Guarantees for Phylogeny Inference from Single-Cell Lineage Tracing

Robert Wang, View ORCID ProfileRichard Zhang, Alex Khodaverdian, Nir Yosef
doi: https://doi.org/10.1101/2021.11.21.469464
Robert Wang
1David R. Cheriton School of Computer Science, University of Waterloo, ON, Canada
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Richard Zhang
2Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, CA, USA
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  • ORCID record for Richard Zhang
Alex Khodaverdian
2Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, CA, USA
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Nir Yosef
1David R. Cheriton School of Computer Science, University of Waterloo, ON, Canada
2Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, CA, USA
3Center for Computational Biology, University of California, Berkeley, CA, USA
4Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA
5Chan Zuckerberg BioHub, San Francisco, CA, USA
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  • For correspondence: niryosef@berkeley.edu
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Abstract

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 Statement

NY is an advisor and/or has equity in Cellarity, Celsius Therapeutics, and Rheos Medicine.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted November 22, 2021.
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Theoretical Guarantees for Phylogeny Inference from Single-Cell Lineage Tracing
Robert Wang, Richard Zhang, Alex Khodaverdian, Nir Yosef
bioRxiv 2021.11.21.469464; doi: https://doi.org/10.1101/2021.11.21.469464
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Theoretical Guarantees for Phylogeny Inference from Single-Cell Lineage Tracing
Robert Wang, Richard Zhang, Alex Khodaverdian, Nir Yosef
bioRxiv 2021.11.21.469464; doi: https://doi.org/10.1101/2021.11.21.469464

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