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Reconstructing B cell lineage trees with minimum spanning tree and genotype abundances.

Nika Abdollahi1,2, Lucile Jeusset1,3, Anne de Septenville3

  • 1UMR 7238, Laboratoire de Biologie Computationnelle et Quantitative, Sorbonne University, Paris, France.

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Summary

ClonalTree efficiently reconstructs B cell lineage trees by incorporating genotype abundance into phylogenetic methods. This approach accurately reflects B cell affinity maturation dynamics, outperforming existing algorithms for high-throughput sequencing data.

Keywords:
B cell receptor repertoireLineage Treephylogenetics

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Area of Science:

  • Immunology
  • Computational Biology
  • Evolutionary Biology

Background:

  • B cell receptor (BCR) genes undergo somatic hypermutations and selection during affinity maturation, creating diverse antibody lineages.
  • Cellular genotype abundance offers insights into the evolutionary dynamics of B cell populations.
  • Existing phylogenetic methods for B cell lineage reconstruction are often time-consuming or neglect cellular abundance data.

Purpose of the Study:

  • To develop a novel, computationally efficient, and accurate method for constructing B cell lineage trees.
  • To integrate cellular genotype abundance into phylogenetic tree inference for B cell affinity maturation.
  • To provide a tool suitable for analyzing high-throughput BCR sequencing data in biomedical research.

Main Methods:

  • Introduced ClonalTree, a low-complexity algorithm integrating genotype abundances into minimum spanning tree (MST) algorithms.
  • Utilized simulated and experimental B cell population data for method validation.
  • Compared ClonalTree's performance against existing MST-based and exhaustive tree-generating methods.

Main Results:

  • ClonalTree accurately reconstructs B cell lineage trees, outperforming standard MST algorithms.
  • The method demonstrates comparable accuracy to exhaustive tree-generating approaches.
  • ClonalTree significantly reduces computational time, being hundreds to thousands of times faster.

Conclusions:

  • ClonalTree offers an accurate and highly efficient solution for B cell lineage tree construction.
  • The method's speed and accuracy make it ideal for large-scale, high-throughput BCR sequencing data analysis.
  • ClonalTree facilitates deeper insights into B cell evolutionary dynamics in biomedical applications.