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Neighbor-Joining algorithm with theoretical guarantees improves CRISPR-Cas9 lineage tracing tree reconstruction

By

Nir Yosef

1d ago· 5 min readenInsight

Summary

This paper presents a theoretical analysis of tree reconstruction from CRISPR-Cas9 lineage tracing data using Neighbor-Joining (NJ) algorithms. The authors develop a moment-matched distance estimation method and prove reconstruction guarantees even when model parameters are unknown and data is missing—a first for CRISPR-Cas9 lineage tracing. They demonstrate improved performance over traditional NJ approaches on both simulated data and real data from a mouse model of lung cancer.

Key quotes

· 4 pulled
We develop a series of tools to analyze this algorithm and prove its theoretical guarantees.
When the parameters of the data generating process are known and there is no missing data, our results align with established results from common evolutionary models, such as Cavender-Farris-Neyman and Jukes-Cantor.
We develop new theory that shows for the first time that it is still possible to obtain reconstruction guarantees in the CRISPR-Cas9 case and in other models of evolution.
Empirically, we show on both simulated lineage tracing data and on real data from a mouse model of lung cancer the improved performance of our method as compared to the traditional use of NJ.
Snippet from the RSS feed
CRISPR-Cas9 based lineage tracing technologies have enabled the reconstruction of single-cell phylogenies from transcriptional readouts. However, developing tree-reconstruction algorithms with theoretical guarantees in this setting is challenging. In this

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