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

Autor: Sofie Gielis, Pieter Moris, Wout Bittremieux, Nicolas De Neuter, Benson Ogunjimi, Kris Laukens, Pieter Meysman
Přispěvatelé: Faculty of Arts and Philosophy, Pediatrics
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
T-Cell Antigen Receptor Specificity/genetics
T-Lymphocytes
Epitopes
T-Lymphocyte

T-Cell Antigen Receptor Specificity
Web Browser
immunoinformatics
Epitope
0302 clinical medicine
Databases
Genetic

Immunology and Allergy
Statistical analysis
Original Research
Repertoire
epitope specificity
hemic and immune systems
vaccines
medicine.anatomical_structure
Algorithms
TCR repertoire analysis
lcsh:Immunologic diseases. Allergy
Receptors
Antigen
T-Cell/genetics

T cell
infectious disease
Immunology
Receptors
Antigen
T-Cell

chemical and pharmacologic phenomena
Computational biology
Biology
Models
Biological

enrichment analysis
Clonal Evolution
03 medical and health sciences
Antigen
medicine
Humans
Amino Acid Sequence
Epitopes
T-Lymphocyte/chemistry

Epitope specificity
Computer. Automation
T-cell receptor
T-Lymphocytes/immunology
Immune state
030104 developmental biology
Clonal Evolution/genetics
cytomegalovirus (CMV)
Human medicine
reproducibility of results
yellow fever virus (YFV)
lcsh:RC581-607
Software
030215 immunology
Zdroj: Frontiers in Immunology, Vol 10 (2019)
Frontiers in Immunology
Frontiers in immunology
ISSN: 1664-3224
DOI: 10.3389/fimmu.2019.02820/full
Popis: 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.
Databáze: OpenAIRE