powerTCR: A model-based approach to comparative analysis of the clone size distribution of the T cell receptor repertoire

Koch, Hillary; Starenki, Dmytro; Cooper, Sara J.; Myers, R; Li, Qunhua

doi:10.1371/journal.pcbi.1006571

Cited by 19 publications

(11 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indexes of diversity (Shannon entropy, Inverted Simpson) and species richness (Chao, ACE) were calculated using the clonalDiversity function (cloneCall = “aa”), and the significance of group differences was tested with the Wilcoxon rank sum test. Hierarchical clustering of samples based on clone size distribution was performed with the function clonesizeDistribution (cloneCall = “aa”) derived from the package PowerTCR ( Koch et al, 2018 ). The proportion of occupied repertoire space was plotted using the function clonalProportion (cloneCall = “aa”), and alluvial plots were generated with compareClonotypes after selecting the top 20 most expanded clonotypes in the tumor.…”

Section: Methodsmentioning

confidence: 99%

Circulating clonally expanded T cells reflect functions of tumor-infiltrating T cells

Lucca

Axisa

et al. 2021

Journal of Experimental Medicine

View full text Add to dashboard Cite

Understanding the relationship between tumor and peripheral immune environments could allow longitudinal immune monitoring in cancer. Here, we examined whether T cells that share the same TCRαβ and are found in both tumor and blood can be interrogated to gain insight into the ongoing tumor T cell response. Paired transcriptome and TCRαβ repertoire of circulating and tumor-infiltrating T cells were analyzed at the single-cell level from matched tumor and blood from patients with metastatic melanoma. We found that in circulating T cells matching clonally expanded tumor-infiltrating T cells (circulating TILs), gene signatures of effector functions, but not terminal exhaustion, reflect those observed in the tumor. In contrast, features of exhaustion are displayed predominantly by tumor-exclusive T cells. Finally, genes associated with a high degree of blood–tumor TCR sharing were overexpressed in tumor tissue after immunotherapy. These data demonstrate that circulating TILs have unique transcriptional patterns that may have utility for the interrogation of T cell function in cancer immunotherapy.

show abstract

Section: Methodsmentioning

confidence: 99%

Circulating clonally expanded T cells reflect functions of tumor-infiltrating T cells

Lucca

Axisa

et al. 2021

Journal of Experimental Medicine

View full text Add to dashboard Cite

show abstract

“…scTCR-seq analysis Joint analysis of single-cell transcriptomes and TCR repertoires was performed by the function of combineExpression from package of scRepertoire v1.14.0 (44). The abundance of cloneTypes were defined based on its frequency (0< Rare <= 1, 1< Small <= 5, 5< Medium <= 20, 20< Large <= 100, 100< Hyperexpanded <= 1,000).…”

Section: Single Cell Transcriptome Analysismentioning

confidence: 99%

Immune signatures underlying post-acute COVID-19 lung sequelae

et al. 2021

View full text Add to dashboard Cite

Severe COVID-19 pneumonia survivors often exhibit long-term pulmonary sequalae, but the underlying mechanisms or associated local and systemic immune correlates are not known. Here, we have performed high-dimensional characterization of the pathophysiological and immune traits of aged COVID-19 convalescents, and correlated the local and systemic immune profiles with pulmonary function and lung imaging. We found that chronic lung impairment was accompanied by persistent respiratory immune alterations. We showed that functional SARS-CoV-2-specific memory T and B cells were enriched at the site of infection compared to those of blood. Detailed evaluation of the lung immune compartment revealed dysregulated respiratory CD8 + T cell responses were associated with the impaired lung function following acute COVID-19. Single cell transcriptomic analysis identified the potential pathogenic subsets of respiratory CD8 + T cells contributing to persistent tissue conditions following COVID-19. Our results have revealed pathophysiological and immune traits that may support the development of lung sequelae following SARS-CoV-2 pneumonia in older individuals, with implications for the treatment of chronic COVID-19 symptoms.

show abstract

“…Jessen-Shannon distance (JSD) is used to evaluate the similarity in repertoire architecture among subsets 20 . We calculated JSD with JSD(), a function included in philentropy () 21 , a R package.…”

Section: Methodsmentioning

confidence: 99%

CD4+ T cell subsets present stable relationships in their T cell receptor repertoires

Wang

2020

Preprint

View full text Add to dashboard Cite

CD4+ T cells are key components of adaptive immunity. The cell differentiation equips CD4+ T cells with new functions. However, the effect of cell differentiation on T cell receptor (TCR) repertoire is not investigated. Here, we examined the features of TCR beta (TCRB) repertoire of the top clones within naive, memory and regular T cell (Treg) subsets: repertoire structure, gene usage, length distribution and sequence composition. First, we found that memory subsets and Treg would be discriminated from naive by the features of TCRB repertoire. Second, we found that the correlations between the features of memory subsets and naive were positively related to differentiation levels of memory subsets. Third, we found that public clones presented a reduced proportion and a skewed sequence composition in differentiated subsets. Furthermore, we found that public clones led naive to recognize a broader spectrum of antigens than other subsets. Our findings suggest that TCRB repertoire of CD4+ T cell subsets is skewed in a differentiation-depended manner. Our findings show that the variations of public clones contribute to these changes. Our findings indicate that the reduction of public clones in differentiation trim the antigen specificity of CD4+ T cells. The study unveils the physiological effect of memory formation and facilitates the selection of proper CD4+ subset for cellular therapy.

show abstract

powerTCR: A model-based approach to comparative analysis of the clone size distribution of the T cell receptor repertoire

Cited by 19 publications

References 35 publications

Circulating clonally expanded T cells reflect functions of tumor-infiltrating T cells

Circulating clonally expanded T cells reflect functions of tumor-infiltrating T cells

Immune signatures underlying post-acute COVID-19 lung sequelae

CD4+ T cell subsets present stable relationships in their T cell receptor repertoires

Contact Info

Product

Resources

About