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T and B Cell Receptor Immune Repertoire Analysis using Next-generation Sequencing
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Comparing T cell receptor repertoires using optimal transport.

Branden J Olson1,2, Stefan A Schattgen3, Paul G Thomas3

  • 1Department of Computational Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.

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|December 8, 2022
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Summary

Comparing T cell receptor (TCR) repertoires is challenging. This study introduces a novel, efficient optimal transport method using Sinkhorn distance and TCRdist to accurately compare TCR repertoires, preserving distributional information.

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Area of Science:

  • Immunology
  • Computational Biology
  • Bioinformatics

Background:

  • T cell receptor (TCR) repertoire comparison is crucial but complex.
  • Existing methods often lose significant distributional information.
  • There is a need for advanced, information-preserving comparison techniques.

Purpose of the Study:

  • To introduce a novel nonparametric approach for comparing empirical TCR repertoires.
  • To leverage optimal transport methods for robust TCR repertoire analysis.
  • To provide a simpler, more informative alternative to current comparison strategies.

Main Methods:

  • Application of the Sinkhorn distance, a fast optimal transport algorithm.
  • Utilization of TCRdist, a recently developed metric for TCR sequence comparison.
  • Nonparametric comparison of empirical TCR repertoire distributions.

Main Results:

  • The proposed method successfully identifies significant differences between distinct TCR distributions.
  • The approach demonstrates effectiveness across several case studies.
  • Performance is competitive with more complex existing methods.

Conclusions:

  • The Sinkhorn distance combined with TCRdist offers an efficient and informative way to compare TCR repertoires.
  • This method retains valuable distributional information lost in simpler approaches.
  • The pipeline is computationally efficient and requires minimal modeling assumptions.