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 work, we derive a reconstruction algorithm with theoretical guarantees using Neighbor-Joining (NJ) on distances that are moment-matched to estimate the true tree distances. We develop a series of tools to analyze this algorithm and prove its theoretical guarantees. 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.

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Tree Reconstruction Guarantees from CRISPR-Cas9 Lineage Tracing Data Using Neighbor-Joining

  • Sebastian Prillo,
  • Kevin An,
  • Wilson Wu,
  • Ivan Kristanto,
  • Matthew G. Jones,
  • Yun S. Song,
  • Nir Yosef

摘要

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 work, we derive a reconstruction algorithm with theoretical guarantees using Neighbor-Joining (NJ) on distances that are moment-matched to estimate the true tree distances. We develop a series of tools to analyze this algorithm and prove its theoretical guarantees. 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.