ClusTCR: a python interface for rapid clustering of large sets of CDR3 sequences with unknown antigen specificity

Valkiers, Sebastiaan; Houcke, Max Van; Laukens, Kris; Meysman, Pieter

doi:10.1093/bioinformatics/btab446

Cited by 48 publications

(62 citation statements)

References 11 publications

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“…Physio-Chemical Properties Amino Acids Nucleotides Frequency Enrichment GIANA [82] (V Only) ALICE [83] clusTCR [84] GLIPH2 [85] iSMART [86] TCRdist [87] (CDR1 and 2) TCRNET [83] (V and J) (control samples required) ImmunoMap [88] MiXCR [51] (V and J) the same antigen, having conserved motifs or similar physiochemical properties (Ta-3). In identifying the clusters related to a particular disease, some methods use the ter frequency or over-representation relative to a control group.…”

Section: Methods Features V(d)j Alignment Cdr3s Short Motifsmentioning

confidence: 99%

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Utility of Bulk T-Cell Receptor Repertoire Sequencing Analysis in Understanding Immune Responses to COVID-19

et al. 2022

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Measuring immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 19 (COVID-19), can rely on antibodies, reactive T cells and other factors, with T-cell-mediated responses appearing to have greater sensitivity and longevity. Because each T cell carries an essentially unique nucleic acid sequence for its T-cell receptor (TCR), we can interrogate sequence data derived from DNA or RNA to assess aspects of the immune response. This review deals with the utility of bulk, rather than single-cell, sequencing of TCR repertoires, considering the importance of study design, in terms of cohort selection, laboratory methods and analysis. The advances in understanding SARS-CoV-2 immunity that have resulted from bulk TCR repertoire sequencing are also be discussed. The complexity of sequencing data obtained by bulk repertoire sequencing makes analysis challenging, but simple descriptive analyses, clonal analysis, searches for specific sequences associated with immune responses to SARS-CoV-2, motif-based analyses, and machine learning approaches have all been applied. TCR repertoire sequencing has demonstrated early expansion followed by contraction of SARS-CoV-2-specific clonotypes, during active infection. Maintenance of TCR repertoire diversity, including the maintenance of diversity of anti-SARS-CoV-2 response, predicts a favourable outcome. TCR repertoire narrowing in severe COVID-19 is most likely a consequence of COVID-19-associated lymphopenia. It has been possible to follow clonotypic sequences longitudinally, which has been particularly valuable for clonotypes known to be associated with SARS-CoV-2 peptide/MHC tetramer binding or with SARS-CoV-2 peptide-induced cytokine responses. Closely related clonotypes to these previously identified sequences have been shown to respond with similar kinetics during infection. A possible superantigen-like effect of the SARS-CoV-2 spike protein has been identified, by means of observing V-segment skewing in patients with severe COVID-19, together with structural modelling. Such a superantigen-like activity, which is apparently absent from other coronaviruses, may be the basis of multisystem inflammatory syndrome and cytokine storms in COVID-19. Bulk TCR repertoire sequencing has proven to be a useful and cost-effective approach to understanding interactions between SARS-CoV-2 and the human host, with the potential to inform the design of therapeutics and vaccines, as well as to provide invaluable pathogenetic and epidemiological insights.

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Section: Methods Features V(d)j Alignment Cdr3s Short Motifsmentioning

confidence: 99%

“…Nucleotides Frequency Enrichment GIANA [82] (V Only) ALICE [83] clusTCR [84] GLIPH2 [85] iSMART [86] TCRdist [87] (CDR1 and 2)…”

Section: Physio-chemical Properties Amino Acidsmentioning

confidence: 99%

Utility of Bulk T-Cell Receptor Repertoire Sequencing Analysis in Understanding Immune Responses to COVID-19

et al. 2022

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“…We used clusTCR 51 to cluster TCRs based on CDR3, ignoring the V, J labels, as well as HLA information. clusTCR uses a two-step clustering approach, using Faiss Clustering Library for speed and Markov Clustering Algorithm (MCL) for accuracy.…”

Section: Methodsmentioning

confidence: 99%

The T cell receptor repertoire reflects the dynamics of the immune response to vaccination

Mohammed

Meadows²,

Hekmaty

et al. 2021

Preprint

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Early, high-resolution metrics are needed to ascertain the immune response to vaccinations. The T cell receptor (TCR), a heterodimer of one α and one β chain, is a promising target, with the complete TCR repertoire reflecting the T cells present in an individual. To this end, we developed Tseek, an unbiased and accurate method for profiling the TCR repertoire by sequencing the TCR α and β chains and developing a suite of tools for repertoire analysis. An added advantage is the ability to non-invasively analyze T cells in peripheral blood mononuclear cells (PBMCs). Tseek and the analytical suite were used to explore the T cell response to both the COVID-19 mRNA vaccine (n=9) and the seasonal inactivated Influenza vaccine (n=5) at several time points. Neutralizing antibody titers were also measured in the covid vaccine samples. The COVID-19 vaccine elicited a broad T cell response involving multiple expanded clones, whereas the Influenza vaccine elicited a narrower response involving fewer clones. Many distinct T cell clones responded at each time point, over a month, providing temporal details lacking in the antibody measurements, especially before the antibodies are detectable. In individuals recovered from a SARS-CoV-2 infection, the first vaccine dose elicited a robust T cell response, while the second dose elicited a comparatively weaker response, indicating a saturation of the response. The physical symptoms experienced by the recipients immediately following the vaccinations were not indicative of the TCR/antibody responses, while a weak TCR response seemed to presage a weak antibody response. We also found that the TCR repertoire acts as an individual fingerprint: donors of blood samples taken years apart could be identified solely based upon their TCR repertoire, hinting at other surprising uses the TCR repertoire may have. These results demonstrate the promise of TCR repertoire sequencing as an early and sensitive measure of the adaptive immune response to vaccination, which can help improve immunogen selection and optimize vaccine dosage and spacing between doses.

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“…In order to identify the same or similar antigen specificity clonal groupings, we analyzed the TRB repertoire of all patients using a reported clustering tool named clusTCR that is available as an anaconda package (https://anaconda.org/svalkiers/clustcr, accessed on 27 October, 2021) [24]. The clusTCR works in two steps, one to allow fast and efficient clustering and a second to perform accurate clustering.…”

Section: Clustering Estimation and Motifs Prediction Of Trb Clonotypesmentioning

confidence: 99%

T-Cell Receptor β Chain and B-Cell Receptor Repertoires in Chronic Hepatitis B Patients with Coexisting HBsAg and Anti-HBs

Zhan

Chang

Wu³

et al. 2022

Pathogens

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Antibodies in response to antigens are related to the immune repertoire of T- and B-cell receptors. However, some patients with chronic hepatitis B (CHB) have coexisting HBsAg and anti-HBsAg antibodies (anti-HBs) that cannot neutralize HBV. We attempted to investigate the repertoires that produce this response in CHB patients. The T-cell receptor β chain (TRB) and B-cell receptor (BCR) repertoires of peripheral blood genomic DNA were analyzed using MiXCR. T-cell receptor (TCR) cluster analysis was carried out by clusTCR, and motifs prediction was selected by Multiple Em for Motif Elicitation (MEME). A total of 76 subjects were enrolled, including 26 HBsAg and anti-HBs coexisting patients with CHB (DP group), 25 anti-HBs single-positive healthy people (SP group), and 25 CHB patients (CHB group). The clone length of BCR in 39, 90 was significantly different among these groups (p = 0.005, 0.036). The motif “CASSLG” in the DP group was significantly higher than SP and CHB groups and may relate to coexistence, and the motif “GAGPLT” was only shown in the SP group and may relate to anti-HB expression. These provide important insights into vaccine development and CHB treatment.

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ClusTCR: a python interface for rapid clustering of large sets of CDR3 sequences with unknown antigen specificity

Cited by 48 publications

References 11 publications

Utility of Bulk T-Cell Receptor Repertoire Sequencing Analysis in Understanding Immune Responses to COVID-19

Utility of Bulk T-Cell Receptor Repertoire Sequencing Analysis in Understanding Immune Responses to COVID-19

The T cell receptor repertoire reflects the dynamics of the immune response to vaccination

T-Cell Receptor β Chain and B-Cell Receptor Repertoires in Chronic Hepatitis B Patients with Coexisting HBsAg and Anti-HBs

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