Use of machine learning to identify a T cell response to SARS-CoV-2

Cell Rep Med. 2021 Feb 16;2(2):100192. doi: 10.1016/j.xcrm.2021.100192. Epub 2021 Jan 16.

Abstract

The identification of SARS-CoV-2-specific T cell receptor (TCR) sequences is critical for understanding T cell responses to SARS-CoV-2. Accordingly, we reanalyze publicly available data from SARS-CoV-2-recovered patients who had low-severity disease (n = 17) and SARS-CoV-2 infection-naive (control) individuals (n = 39). Applying a machine learning approach to TCR beta (TRB) repertoire data, we can classify patient/control samples with a training sensitivity, specificity, and accuracy of 88.2%, 100%, and 96.4% and a testing sensitivity, specificity, and accuracy of 82.4%, 97.4%, and 92.9%, respectively. Interestingly, the same machine learning approach cannot separate SARS-CoV-2 recovered from SARS-CoV-2 infection-naive individual samples on the basis of B cell receptor (immunoglobulin heavy chain; IGH) repertoire data, suggesting that the T cell response to SARS-CoV-2 may be more stereotyped and longer lived. Following validation in larger cohorts, our method may be useful in detecting protective immunity acquired through natural infection or in determining the longevity of vaccine-induced immunity.

Keywords: B cell receptor repertoire; SARS-CoV-2; T cell receptor repertoire; adaptive immunity; antibody; coronavirus; hierarchical clustering; infection; machine learning.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • COVID-19 / immunology*
  • COVID-19 / pathology
  • COVID-19 / virology
  • Cluster Analysis
  • Complementarity Determining Regions / chemistry
  • Complementarity Determining Regions / genetics
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Machine Learning*
  • Principal Component Analysis
  • Receptors, Antigen, B-Cell / chemistry
  • Receptors, Antigen, B-Cell / metabolism
  • Receptors, Antigen, T-Cell / chemistry
  • Receptors, Antigen, T-Cell / metabolism
  • SARS-CoV-2 / immunology
  • SARS-CoV-2 / isolation & purification
  • Sequence Analysis, DNA
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*

Substances

  • Complementarity Determining Regions
  • Receptors, Antigen, B-Cell
  • Receptors, Antigen, T-Cell