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Genotypic Inference of HIV-1 Tropism Using Population-based Sequencing of V3
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Benchmarking Tree and Ancestral Sequence Inference for B Cell Receptor Sequences.

Kristian Davidsen1, Frederick A Matsen1

  • 1Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA, United States.

Frontiers in Immunology
|November 16, 2018
PubMed
Summary
This summary is machine-generated.

Phylogenetic tools for B cell receptor evolution vary in accuracy. New B cell-specific tools offer improvements, but modeling unique mutation processes yields the greatest gains for reconstructing ancestral sequences.

Keywords:
B cell receptor repertoireancestral sequence reconstructionantibodiesbenchmarkingphylogeny

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Area of Science:

  • Immunology
  • Computational Biology
  • Evolutionary Biology

Background:

  • B cell receptor (BCR) sequences undergo affinity maturation via mutation and selection.
  • Phylogenetic tools are crucial for reconstructing BCR evolution and ancestral sequences.
  • The performance of standard phylogenetic methods on BCR data is not well understood.

Purpose of the Study:

  • To benchmark classical and novel phylogenetic tools for BCR sequence analysis.
  • To evaluate the impact of B cell-specific evolutionary features on phylogenetic inference.
  • To assess the performance gains offered by B cell-specific tools over classical methods.

Main Methods:

  • Simulating BCR sequences using a forward-time model of affinity maturation.
  • Benchmarking tree structure and ancestral sequence inference accuracy of various phylogenetic tools.
  • Validating findings with real BCR data, incorporating isotype switching rules.

Main Results:

  • Significant variation exists in tree topology and ancestral sequence accuracy among tested phylogenetic tools.
  • Classical phylogenetic methods show limitations when applied to BCR sequences.
  • Newer B cell-specific tools demonstrate improved performance, with further gains from modeling unique BCR mutation processes.

Conclusions:

  • Current phylogenetic tools exhibit substantial performance differences for BCR sequence analysis.
  • There is a clear need for methods that account for the specific mutation patterns in B cell evolution.
  • Optimizing phylogenetic approaches for BCRs can significantly enhance the accuracy of evolutionary reconstructions.