VDJtools: Unifying Post-analysis of T Cell Receptor Repertoires

Shugay, Mikhail; Bagaev, Dmitriy V.; Turchaninova, Maria A.; Bolotin, Dmitriy A.; Britanova, Olga V.; Putintseva, Ekaterina V.; Pogorelyy, Mikhail V.; Nazarov, Vadim; Zvyagin, Ivan V.; Kirgizova, Vitalina; Киргизов, К. И.; Скоробогатова, Е. В.; Chudakov, Dmitriy M.

doi:10.1371/journal.pcbi.1004503

Cited by 528 publications

(478 citation statements)

References 62 publications

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“…SPSS Statistics 20 (IBM, Armonk, NY), GraphPad 7 (La Jolla, CA) or R Project Package in VDJTools environment were used for figures and analyses. 47 Significance was set at 0.05.…”

Section: Resultsmentioning

confidence: 99%

“…Weak correlations between pre-and post-AHSCT clonotypes indicate low repertoire overlap and high renewal of the immune system. 47 Individual patient scatter plots show that at 6-months post-AHSCT, repertoire overlaps were lower in the responder (representative patient 1, r 2 , 0.09) than in the nonresponder patients (representative patient 5, r 2 . 0.51) ( Figure 2E; supplemental In transplanted patients, higher percentages of Tregs were detected at 6 (P 5 .01), 12 (P , .01), and 18 (P 5 .03) months after AHSCT when compared with pretransplant levels ( Figure 3A).…”

Section: Low Clonotype Overlap and High Tcr Diversity Are Related Tomentioning

confidence: 99%

“…46 Postanalysis of TCR repertoire diversity, segment usage, spectratyping, clonotype tracking, and repertoire overlap were performed by VDJTools. 47 Raw sequencing data were deposited in the NCBI SRA database (SRP106516).…”

Section: Analysis Of Tcrb Repertoire By Ngsmentioning

confidence: 99%

“…47 Minimal transplant-induced changes in the TCR repertoire and clonotype specificities were assessed by NGS. 28,51 At 1-year posttransplantation, the TCR diversity had significantly increased from pretransplant levels, indicating the generation of a new immune system ( Figure 2A).…”

Section: Low Clonotype Overlap and High Tcr Diversity Are Related Tomentioning

confidence: 99%

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Immune rebound associates with a favorable clinical response to autologous HSCT in systemic sclerosis patients

et al. 2018

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• Clinical response of SSc patients after AHSCT is associated with thymic and bone marrow rebounds.• Responder patients showed higher Treg and Breg counts and lower pre-/post-AHSCT TCR repertoire overlap than nonresponder patients. compared with pretransplant levels. In parallel, increased bone marrow output of newly generated naive B-cells, starting at 6 months after AHSCT, renovated the B-cell populations in peripheral blood. At 6 and 12 months after AHSCT, Bregs increased and produced higher interleukin-10 levels than before transplant. When the nonresponder patients were evaluated separately, Treg and Breg counts did not increase after AHSCT, and high TCR repertoire overlap between pre-and posttransplant periods indicated maintenance of underlying disease mechanisms. These data suggest that clinical improvement of SSc patients is related to increased counts of newly generated Tregs and Bregs after AHSCT as a result of coordinated thymic and bone marrow rebound.

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“…SPSS Statistics 20 (IBM, Armonk, NY), GraphPad 7 (La Jolla, CA) or R Project Package in VDJTools environment were used for figures and analyses. 47 Significance was set at 0.05.…”

Section: Resultsmentioning

confidence: 99%

Section: Low Clonotype Overlap and High Tcr Diversity Are Related Tomentioning

confidence: 99%

Section: Analysis Of Tcrb Repertoire By Ngsmentioning

confidence: 99%

Section: Low Clonotype Overlap and High Tcr Diversity Are Related Tomentioning

confidence: 99%

See 2 more Smart Citations

Immune rebound associates with a favorable clinical response to autologous HSCT in systemic sclerosis patients

et al. 2018

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“…This measure accounts for both overall overlap size and correlation of overlapping clonotype frequencies (42).…”

Section: Tcrb Libraries Preparation and Data Analysismentioning

confidence: 99%

Dynamics of Individual T Cell Repertoires: From Cord Blood to Centenarians

Britanova

Shugay

Merzlyak

et al. 2016

The Journal of Immunology

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162

198

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The diversity, architecture, and dynamics of the TCR repertoire largely determine our ability to effectively withstand infections and malignancies with minimal mistargeting of immune responses. In this study, we have employed deep TCRβ repertoire sequencing with normalization based on unique molecular identifiers to explore the long-term dynamics of T cell immunity. We demonstrate remarkable stability of repertoire, where approximately half of all T cells in peripheral blood are represented by clones that persist and generally preserve their frequencies for 3 y. We further characterize the extremes of lifelong TCR repertoire evolution, analyzing samples ranging from umbilical cord blood to centenarian peripheral blood. We show that the fetal TCR repertoire, albeit structurally maintained within regulated borders due to the lower numbers of randomly added nucleotides, is not limited with respect to observed functional diversity. We reveal decreased efficiency of nonsense-mediated mRNA decay in umbilical cord blood, which may reflect specific regulatory mechanisms in development. Furthermore, we demonstrate that human TCR repertoires are functionally more similar at birth but diverge during life, and we track the lifelong behavior of CMV- and EBV-specific T cell clonotypes. Finally, we reveal gender differences in dynamics of TCR diversity constriction, which come to naught in the oldest age. Based on our data, we propose a more general explanation for the previous observations on the relationships between longevity and immunity.

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High‐throughput sequencing of immune repertoires in multiple sclerosis

Lossius

Johansen

Vartdal

et al. 2016

Ann Clin Transl Neurol

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T cells and B cells are crucial in the initiation and maintenance of multiple sclerosis (MS), and the activation of these cells is believed to be mediated through specific recognition of antigens by the T‐ and B‐cell receptors. The antigen receptors are highly polymorphic due to recombination (T‐ and B‐cell receptors) and mutation (B‐cell receptors) of the encoding genes, which can therefore be used as fingerprints to track individual T‐ and B‐cell clones. Such studies can shed light on mechanisms driving the immune responses and provide new insights into the pathogenesis. Here, we summarize studies that have explored the T‐ and B‐cell receptor repertoires using earlier methodological approaches, and we focus on how high‐throughput sequencing has provided new knowledge by surveying the immune repertoires in MS in even greater detail and with unprecedented depth.

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VDJtools: Unifying Post-analysis of T Cell Receptor Repertoires

Cited by 528 publications

References 62 publications

Immune rebound associates with a favorable clinical response to autologous HSCT in systemic sclerosis patients

Immune rebound associates with a favorable clinical response to autologous HSCT in systemic sclerosis patients

Dynamics of Individual T Cell Repertoires: From Cord Blood to Centenarians

High‐throughput sequencing of immune repertoires in multiple sclerosis

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