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Theoretical guarantees for phylogeny inference from single-cell lineage tracing.

Robert Wang1, Richard Zhang2, Alex Khodaverdian2

  • 1Algorithms and Complexity Group, David R. Cheriton School of Computer Science, University of Waterloo, Waterloo ON N2L 3G1, Canada.

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|March 17, 2023
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Summary

This study introduces new algorithms for reconstructing cell lineages using CRISPR-Cas9 technology. These methods improve the accuracy of tracing cell relationships during development, offering insights for experimental design.

Keywords:
Crispr-Cas9computational phylogeneticssingle-cell lineage tracing

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Area of Science:

  • Genomics
  • Developmental Biology
  • Computational Biology

Background:

  • CRISPR-Cas9 genome editing enables lineage tracing for single-cell developmental studies.
  • Reconstructing clonal relationships is challenging due to data complexities like cutting rates and indel diversity.

Purpose of the Study:

  • Develop algorithms for accurate single-cell phylogenetic tree reconstruction.
  • Establish theoretical bounds on recording sites needed for precise phylogeny.
  • Analyze how experimental parameters affect reconstruction difficulty.

Main Methods:

  • Developed two theoretically grounded algorithms for phylogenetic reconstruction.
  • Derived asymptotic bounds for the number of recording sites.
  • Conducted simulations to evaluate algorithm performance and bound validity.

Main Results:

  • Algorithms demonstrate effective reconstruction of single-cell phylogenetic trees.
  • Asymptotic bounds provide guidance on necessary recording sites for accurate phylogeny.
  • Simulations confirm empirical performance aligns with theoretical trends.

Conclusions:

  • This work offers a theoretical framework for phylogenetic reconstruction in CRISPR-Cas9 lineage tracing.
  • Findings have implications for optimizing experimental design in developmental studies.
  • The developed algorithms and bounds enhance the utility of CRISPR-Cas9 for lineage tracing.