tetano
Editor, Senior Moderator
Comput Struct Biotechnol J
. 2023 Jan 27.
doi: 10.1016/j.csbj.2023.01.038. Online ahead of print.
CoV2-TCR: a web server for screening TCR CDR3 from TCR immune repertoire of COVID-19 patients and their recognized SARS-CoV-2 epitopes
Xingxing Jian[SUP] 1 [/SUP], Yu Zhang[SUP] 2 3 [/SUP], Jingjing Zhao[SUP] 2 4 [/SUP], Zhuoming Zhao[SUP] 2 4 [/SUP], Manman Lu[SUP] 2 [/SUP], Lu Xie[SUP] 1 2 [/SUP]
Affiliations
Abstract
Although multiple vaccines have been developed and widely administered, several severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants were reported to evade immune responses and spread diffusely. Here, 108 RNA-seq files from coronavirus disease 2019 (COVID-19) patients and healthy donors (HD) were downloaded to extract TCR immune repertoire by MiXCR. Those extracted TCR repertoires were compared and found that the disease progression was related negatively with the diversity and positively with the clonality. Particularly, higher proportions of high-abundance clonotypes were observed in active and severe COVID-19 samples, probably resulting from strong stimulus of SARS-CoV-2 epitopes and continued immune response in host. To investigate the specific recognition between TCR CDR3 and SARS-CoV-2 epitopes, we constructed an accurate classifier CoV2-TCR with an AUC of 0.967 in an independent dataset, which outperformed several similar tools. Based on this model CoV2-TCR, we observed a huge range in the number of those TCR CDR3 recognizing those different predicted peptides, including 28 MHC-I epitopes from SARS-CoV-2 and 22 immunogenic peptides from SARS-CoV-2 variants. Interestingly, their proportions of high-abundance, low-abundance and rare clonotypes were close for each peptide. To expand application of this model, we established webserver CoV2-TCR, in which users can obtain those recognizing CDR3 sequences from TCR repertoire of COVID-19 patients based on the 9-mer peptides containing mutation site(s) on the four main proteins of SARS-CoV-2 variants. Overall, this study provides preliminary screening for candidate antigen epitopes and the TCR CDR3 that can recognize them, which is helpful for vaccine design on SARS-CoV-2 variants.
Keywords: Antigen epitope; CoV2-TCR; Complementary determining regions 3 (CDR3); Coronavirus disease 2019 (COVID-19); Immunogenic peptide; Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); T cell receptor (TCR).
. 2023 Jan 27.
doi: 10.1016/j.csbj.2023.01.038. Online ahead of print.
CoV2-TCR: a web server for screening TCR CDR3 from TCR immune repertoire of COVID-19 patients and their recognized SARS-CoV-2 epitopes
Xingxing Jian[SUP] 1 [/SUP], Yu Zhang[SUP] 2 3 [/SUP], Jingjing Zhao[SUP] 2 4 [/SUP], Zhuoming Zhao[SUP] 2 4 [/SUP], Manman Lu[SUP] 2 [/SUP], Lu Xie[SUP] 1 2 [/SUP]
Affiliations
- PMID: 36741787
- PMCID: PMC9882952
- DOI: 10.1016/j.csbj.2023.01.038
Abstract
Although multiple vaccines have been developed and widely administered, several severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants were reported to evade immune responses and spread diffusely. Here, 108 RNA-seq files from coronavirus disease 2019 (COVID-19) patients and healthy donors (HD) were downloaded to extract TCR immune repertoire by MiXCR. Those extracted TCR repertoires were compared and found that the disease progression was related negatively with the diversity and positively with the clonality. Particularly, higher proportions of high-abundance clonotypes were observed in active and severe COVID-19 samples, probably resulting from strong stimulus of SARS-CoV-2 epitopes and continued immune response in host. To investigate the specific recognition between TCR CDR3 and SARS-CoV-2 epitopes, we constructed an accurate classifier CoV2-TCR with an AUC of 0.967 in an independent dataset, which outperformed several similar tools. Based on this model CoV2-TCR, we observed a huge range in the number of those TCR CDR3 recognizing those different predicted peptides, including 28 MHC-I epitopes from SARS-CoV-2 and 22 immunogenic peptides from SARS-CoV-2 variants. Interestingly, their proportions of high-abundance, low-abundance and rare clonotypes were close for each peptide. To expand application of this model, we established webserver CoV2-TCR, in which users can obtain those recognizing CDR3 sequences from TCR repertoire of COVID-19 patients based on the 9-mer peptides containing mutation site(s) on the four main proteins of SARS-CoV-2 variants. Overall, this study provides preliminary screening for candidate antigen epitopes and the TCR CDR3 that can recognize them, which is helpful for vaccine design on SARS-CoV-2 variants.
Keywords: Antigen epitope; CoV2-TCR; Complementary determining regions 3 (CDR3); Coronavirus disease 2019 (COVID-19); Immunogenic peptide; Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); T cell receptor (TCR).