Machine-Learning-Assisted Analysis of TCR Profiling Data Unveils Cross-Reactivity between SARS-CoV-2 and a Wide Spectrum of Pathogens and Other Diseases.
Georgios K Georgakilas, Achilleas P Galanopoulos, Zafeiris Tsinaris, Maria Kyritsi, Varvara A Mouchtouri, Matthaios Speletas, Christos Hadjichristodoulou
Author Information
Georgios K Georgakilas: Laboratory of Hygiene and Epidemiology, Faculty of Medicine, University of Thessaly, 41222 Larisa, Greece.
Achilleas P Galanopoulos: Laboratory of Hygiene and Epidemiology, Faculty of Medicine, University of Thessaly, 41222 Larisa, Greece.
Zafeiris Tsinaris: Laboratory of Hygiene and Epidemiology, Faculty of Medicine, University of Thessaly, 41222 Larisa, Greece.
Maria Kyritsi: Laboratory of Hygiene and Epidemiology, Faculty of Medicine, University of Thessaly, 41222 Larisa, Greece. ORCID
Varvara A Mouchtouri: Laboratory of Hygiene and Epidemiology, Faculty of Medicine, University of Thessaly, 41222 Larisa, Greece. ORCID
Matthaios Speletas: Department of Immunology & Histocompatibility, Faculty of Medicine, University of Thessaly, 41500 Larisa, Greece. ORCID
Christos Hadjichristodoulou: Laboratory of Hygiene and Epidemiology, Faculty of Medicine, University of Thessaly, 41222 Larisa, Greece.
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 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.
