Machine-Learning-Assisted Analysis of TCR Profiling Data Unveils Cross-Reactivity between SARS-CoV-2 and a Wide Spectrum of Pathogens and Other Diseases

During the last two years, the emergence of SARS-CoV-2 has led to millions of deaths worldwide, with a devastating socio-economic impact on a global scale. The scientific community’s focus has recently shifted towards the association of the T cell immunological repertoire with COVID-19 progression a...

Full description

Bibliographic Details
Main Authors: Georgios K. Georgakilas, Achilleas P. Galanopoulos, Zafeiris Tsinaris, Maria Kyritsi, Varvara A. Mouchtouri, Matthaios Speletas, Christos Hadjichristodoulou
Format: Article
Language:English
Published: MDPI AG 2022-10-01
Series:Biology
Subjects:
Online Access:https://www.mdpi.com/2079-7737/11/10/1531
_version_ 1797475085774225408
author Georgios K. Georgakilas
Achilleas P. Galanopoulos
Zafeiris Tsinaris
Maria Kyritsi
Varvara A. Mouchtouri
Matthaios Speletas
Christos Hadjichristodoulou
author_facet Georgios K. Georgakilas
Achilleas P. Galanopoulos
Zafeiris Tsinaris
Maria Kyritsi
Varvara A. Mouchtouri
Matthaios Speletas
Christos Hadjichristodoulou
author_sort Georgios K. Georgakilas
collection DOAJ
description During the last two years, the emergence of SARS-CoV-2 has led to millions of deaths worldwide, with a devastating socio-economic impact on a global scale. The scientific community’s focus has recently shifted towards the association of the T cell immunological repertoire with COVID-19 progression and severity, by utilising T cell receptor sequencing (TCR-Seq) assays. The Multiplexed Identification of T cell Receptor Antigen (MIRA) dataset, which is a subset of the immunoACCESS study, provides thousands of TCRs that can specifically recognise SARS-CoV-2 epitopes. Our study proposes a novel Machine Learning (ML)-assisted approach for analysing TCR-Seq data from the antigens’ point of view, with the ability to unveil key antigens that can accurately distinguish between MIRA COVID-19-convalescent and healthy individuals based on differences in the triggered immune response. Some SARS-CoV-2 antigens were found to exhibit equal levels of recognition by MIRA TCRs in both convalescent and healthy cohorts, leading to the assumption of putative cross-reactivity between SARS-CoV-2 and other infectious agents. This hypothesis was tested by combining MIRA with other public TCR profiling repositories that host assays and sequencing data concerning a plethora of pathogens. Our study provides evidence regarding putative cross-reactivity between SARS-CoV-2 and a wide spectrum of pathogens and diseases, with <i>M. tuberculosis</i> and Influenza virus exhibiting the highest levels of cross-reactivity. These results can potentially shift the emphasis of immunological studies towards an increased application of TCR profiling assays that have the potential to uncover key mechanisms of cell-mediated immune response against pathogens and diseases.
first_indexed 2024-03-09T20:40:05Z
format Article
id doaj.art-a7a528df042f47ad846b50696730f7dc
institution Directory Open Access Journal
issn 2079-7737
language English
last_indexed 2024-03-09T20:40:05Z
publishDate 2022-10-01
publisher MDPI AG
record_format Article
series Biology
spelling doaj.art-a7a528df042f47ad846b50696730f7dc2023-11-23T23:01:06ZengMDPI AGBiology2079-77372022-10-011110153110.3390/biology11101531Machine-Learning-Assisted Analysis of TCR Profiling Data Unveils Cross-Reactivity between SARS-CoV-2 and a Wide Spectrum of Pathogens and Other DiseasesGeorgios K. Georgakilas0Achilleas P. Galanopoulos1Zafeiris Tsinaris2Maria Kyritsi3Varvara A. Mouchtouri4Matthaios Speletas5Christos Hadjichristodoulou6Laboratory of Hygiene and Epidemiology, Faculty of Medicine, University of Thessaly, 41222 Larisa, GreeceLaboratory of Hygiene and Epidemiology, Faculty of Medicine, University of Thessaly, 41222 Larisa, GreeceLaboratory of Hygiene and Epidemiology, Faculty of Medicine, University of Thessaly, 41222 Larisa, GreeceLaboratory of Hygiene and Epidemiology, Faculty of Medicine, University of Thessaly, 41222 Larisa, GreeceLaboratory of Hygiene and Epidemiology, Faculty of Medicine, University of Thessaly, 41222 Larisa, GreeceDepartment of Immunology & Histocompatibility, Faculty of Medicine, University of Thessaly, 41500 Larisa, GreeceLaboratory of Hygiene and Epidemiology, Faculty of Medicine, University of Thessaly, 41222 Larisa, GreeceDuring the last two years, the emergence of SARS-CoV-2 has led to millions of deaths worldwide, with a devastating socio-economic impact on a global scale. The scientific community’s focus has recently shifted towards the association of the T cell immunological repertoire with COVID-19 progression and severity, by utilising T cell receptor sequencing (TCR-Seq) assays. The Multiplexed Identification of T cell Receptor Antigen (MIRA) dataset, which is a subset of the immunoACCESS study, provides thousands of TCRs that can specifically recognise SARS-CoV-2 epitopes. Our study proposes a novel Machine Learning (ML)-assisted approach for analysing TCR-Seq data from the antigens’ point of view, with the ability to unveil key antigens that can accurately distinguish between MIRA COVID-19-convalescent and healthy individuals based on differences in the triggered immune response. Some SARS-CoV-2 antigens were found to exhibit equal levels of recognition by MIRA TCRs in both convalescent and healthy cohorts, leading to the assumption of putative cross-reactivity between SARS-CoV-2 and other infectious agents. This hypothesis was tested by combining MIRA with other public TCR profiling repositories that host assays and sequencing data concerning a plethora of pathogens. Our study provides evidence regarding putative cross-reactivity between SARS-CoV-2 and a wide spectrum of pathogens and diseases, with <i>M. tuberculosis</i> and Influenza virus exhibiting the highest levels of cross-reactivity. These results can potentially shift the emphasis of immunological studies towards an increased application of TCR profiling assays that have the potential to uncover key mechanisms of cell-mediated immune response against pathogens and diseases.https://www.mdpi.com/2079-7737/11/10/1531COVID-19T cell receptorpathogensdiseasescross-reactivity phenomenonMachine Learning
spellingShingle Georgios K. Georgakilas
Achilleas P. Galanopoulos
Zafeiris Tsinaris
Maria Kyritsi
Varvara A. Mouchtouri
Matthaios Speletas
Christos Hadjichristodoulou
Machine-Learning-Assisted Analysis of TCR Profiling Data Unveils Cross-Reactivity between SARS-CoV-2 and a Wide Spectrum of Pathogens and Other Diseases
Biology
COVID-19
T cell receptor
pathogens
diseases
cross-reactivity phenomenon
Machine Learning
title Machine-Learning-Assisted Analysis of TCR Profiling Data Unveils Cross-Reactivity between SARS-CoV-2 and a Wide Spectrum of Pathogens and Other Diseases
title_full Machine-Learning-Assisted Analysis of TCR Profiling Data Unveils Cross-Reactivity between SARS-CoV-2 and a Wide Spectrum of Pathogens and Other Diseases
title_fullStr Machine-Learning-Assisted Analysis of TCR Profiling Data Unveils Cross-Reactivity between SARS-CoV-2 and a Wide Spectrum of Pathogens and Other Diseases
title_full_unstemmed Machine-Learning-Assisted Analysis of TCR Profiling Data Unveils Cross-Reactivity between SARS-CoV-2 and a Wide Spectrum of Pathogens and Other Diseases
title_short Machine-Learning-Assisted Analysis of TCR Profiling Data Unveils Cross-Reactivity between SARS-CoV-2 and a Wide Spectrum of Pathogens and Other Diseases
title_sort machine learning assisted analysis of tcr profiling data unveils cross reactivity between sars cov 2 and a wide spectrum of pathogens and other diseases
topic COVID-19
T cell receptor
pathogens
diseases
cross-reactivity phenomenon
Machine Learning
url https://www.mdpi.com/2079-7737/11/10/1531
work_keys_str_mv AT georgioskgeorgakilas machinelearningassistedanalysisoftcrprofilingdataunveilscrossreactivitybetweensarscov2andawidespectrumofpathogensandotherdiseases
AT achilleaspgalanopoulos machinelearningassistedanalysisoftcrprofilingdataunveilscrossreactivitybetweensarscov2andawidespectrumofpathogensandotherdiseases
AT zafeiristsinaris machinelearningassistedanalysisoftcrprofilingdataunveilscrossreactivitybetweensarscov2andawidespectrumofpathogensandotherdiseases
AT mariakyritsi machinelearningassistedanalysisoftcrprofilingdataunveilscrossreactivitybetweensarscov2andawidespectrumofpathogensandotherdiseases
AT varvaraamouchtouri machinelearningassistedanalysisoftcrprofilingdataunveilscrossreactivitybetweensarscov2andawidespectrumofpathogensandotherdiseases
AT matthaiosspeletas machinelearningassistedanalysisoftcrprofilingdataunveilscrossreactivitybetweensarscov2andawidespectrumofpathogensandotherdiseases
AT christoshadjichristodoulou machinelearningassistedanalysisoftcrprofilingdataunveilscrossreactivitybetweensarscov2andawidespectrumofpathogensandotherdiseases