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Accurate and Efficient Cell Lineage Tree Inference from Noisy Single Cell Data: the Maximum Likelihood Perfect Phylogeny Approach

View ORCID ProfileYufeng Wu
doi: https://doi.org/10.1101/742395
Yufeng Wu
Department of Computer Science and Engineering, University of Connecticut, Storrs, CT 06269, U.S.A.
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  • For correspondence: yufeng.wu@uconn.edu
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Abstract

Cells in an organism share a common evolutionary history, called cell lineage tree. Cell lineage tree can be inferred from single cell genotypes at genomic variation sites. Cell lineage tree inference from noisy single cell data is a challenging computational problem. Most existing methods for cell lineage tree inference assume uniform uncertainty in genotypes. A key missing aspect is that real single cell data usually has non-uniform uncertainty in individual genotypes. Moreover, existing methods are often sampling-based and can be very slow for large data.

In this paper, we propose a new method called ScisTree, which infers cell lineage tree and calls genotypes from noisy single cell genotype data. Different from most existing approaches, ScisTree works with genotype probabilities of individual genotypes (which can be computed by existing single cell genotype callers). ScisTree assumes the infinite sites model. Given uncertain genotypes with individualized probabilities, ScisTree implements a fast heuristic for inferring cell lineage tree and calling the genotypes that allow the so-called perfect phylogeny and maximize the likelihood of the genotypes. Through simulation, we show that ScisTree performs well on the accuracy of inferred trees, and is much more efficient than existing methods. The efficiency of ScisTree enables new applications including imputation of the so-called doublets.

Availability The program ScisTree is available for download at: https://github.com/yufengwudcs/ScisTree

Contact yufeng.wu{at}uconn.edu

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-NC-ND 4.0 International license.
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Posted August 21, 2019.
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Accurate and Efficient Cell Lineage Tree Inference from Noisy Single Cell Data: the Maximum Likelihood Perfect Phylogeny Approach
Yufeng Wu
bioRxiv 742395; doi: https://doi.org/10.1101/742395
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Accurate and Efficient Cell Lineage Tree Inference from Noisy Single Cell Data: the Maximum Likelihood Perfect Phylogeny Approach
Yufeng Wu
bioRxiv 742395; doi: https://doi.org/10.1101/742395

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