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Single cell lineage reconstruction using distance-based algorithms and the R package, DCLEAR.

Wuming Gong1, Hyunwoo J Kim2, Daniel J Garry1

  • 1Lillehei Heart Institute, University of Minnesota, Minneapolis, USA.

BMC Bioinformatics
|March 25, 2022
PubMed
Summary

DCLEAR, a new R package, enhances single-cell lineage reconstruction using advanced CRISPR gene editing data. It introduces novel distance estimation methods, outperforming traditional approaches for accurate cell lineage tree prediction.

Keywords:
Cell lineage tracingLineage reconstructionMachine learningSimulation

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Area of Science:

  • Computational Biology
  • Genomics
  • Bioinformatics

Background:

  • CRISPR gene editing enables cell lineage tree prediction via edited barcodes.
  • Assessing the performance of existing cell lineage reconstruction methods is crucial.
  • The Cell Lineage Reconstruction Dream Challenge (2020) spurred advancements in the field.

Purpose of the Study:

  • To develop and present the DCLEAR R package for single-cell lineage reconstruction.
  • To introduce novel methods for distance matrix estimation in lineage reconstruction.
  • To evaluate the performance of new distance methods against traditional ones.

Main Methods:

  • DCLEAR employs a two-step approach: distance matrix estimation and tree reconstruction.
  • Two novel methods for distance matrix estimation were developed and implemented in DCLEAR.
  • The R package contains the code for these methods, submitted to a challenge competition.

Main Results:

  • The novel distance estimation methods in DCLEAR significantly improve performance over the Hamming distance.
  • DCLEAR's methods were validated through participation in the Cell Lineage Reconstruction Dream Challenge, winning two sub-challenges.
  • The package provides open-source R code for reproducible research.

Conclusions:

  • DCLEAR offers a powerful and effective resource for single-cell lineage reconstruction.
  • The package facilitates accurate cell lineage tree prediction using advanced computational methods.
  • DCLEAR is freely available, promoting wider adoption and research in the field.