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Detection of Enriched T Cell Epitope Specificity in Full T Cell Receptor Sequence Repertoires

Authors: Sofie Gielis; Sofie Gielis; Sofie Gielis; Pieter Moris; Pieter Moris; Wout Bittremieux; Wout Bittremieux; +14 Authors

Detection of Enriched T Cell Epitope Specificity in Full T Cell Receptor Sequence Repertoires

Abstract

High-throughput T cell receptor (TCR) sequencing allows the characterization of an individual's TCR repertoire and directly queries their immune state. However, it remains a non-trivial task to couple these sequenced TCRs to their antigenic targets. In this paper, we present a novel strategy to annotate full TCR sequence repertoires with their epitope specificities. The strategy is based on a machine learning algorithm to learn the TCR patterns common to the recognition of a specific epitope. These results are then combined with a statistical analysis to evaluate the occurrence of specific epitope-reactive TCR sequences per epitope in repertoire data. In this manner, we can directly study the capacity of full TCR repertoires to target specific epitopes of the relevant vaccines or pathogens. We demonstrate the usability of this approach on three independent datasets related to vaccine monitoring and infectious disease diagnostics by independently identifying the epitopes that are targeted by the TCR repertoire. The developed method is freely available as a web tool for academic use at tcrex.biodatamining.be.

Country
Belgium
Keywords

Receptors, Antigen, T-Cell/genetics, T-Cell Antigen Receptor Specificity/genetics, infectious disease, T-Lymphocytes, Immunology, Receptors, Antigen, T-Cell, Epitopes, T-Lymphocyte, T-Cell Antigen Receptor Specificity, Web Browser, immunoinformatics, Models, Biological, enrichment analysis, Clonal Evolution, Databases, Genetic, Humans, Epitopes, T-Lymphocyte/chemistry, Amino Acid Sequence, Computer. Automation, epitope specificity, Reproducibility of Results, T-Lymphocytes/immunology, vaccines, RC581-607, Clonal Evolution/genetics, reproducibility of results, Human medicine, Immunologic diseases. Allergy, Algorithms, Software, TCR repertoire analysis

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
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151
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