Antigen Receptor Galaxy: A User-Friendly, Web-Based Tool for Analysis and Visualization of T and B Cell Receptor Repertoire Data

IJspeert, Hanna; Schouwenburg, Pauline A. van; Zessen, David van; Pico-Knijnenburg, Ingrid; Stubbs, Andrew; Burg, Mirjam van der

doi:10.4049/jimmunol.1601921

Cited by 44 publications

(37 citation statements)

References 30 publications

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“…Data analysis was performed as previously described by IJspeert et al 2016 13 . In short, sequences were demultiplexed based on their multiplex identifier sequence and trimmed using the Antigen Receptor Galaxy (ARGalaxy) tool 34 . Fasta files were uploaded in IMGT/High V‐Quest, 35 and subsequently, the IMGT output files were analyzed in the IGGalaxy tool.…”

Section: Methodsmentioning

confidence: 99%

“…To exclude low‐quality reads, we only included transcripts of which the exact CDR1‐CDR3 nucleotide sequence occurred twice or more 14 . Information on junction characteristics, CDR3 length, and composition were extracted from the output provided by IMGT/High V quest using ARGalaxy 34 . Of each unique clone, the position and frequency of mutations were determined within the IGHV gene (CDR1‐FR3).…”

Section: Methodsmentioning

confidence: 99%

“…13 In short, sequences were demultiplexed based on their multiplex identifier sequence and trimmed using the Antigen Receptor Galaxy (ARGalaxy) tool. 34 Fasta files were uploaded in IMGT/High V-Quest, 35 and subsequently, the IMGT output files were analyzed in the IGGalaxy tool. To exclude low-quality reads, we only included transcripts of which the exact CDR1-CDR3 nucleotide sequence occurred twice or more.…”

Section: Sanger Sequencing Of Igh Gene Rearrangements From Pbmcmentioning

confidence: 99%

“…14 Information on junction characteristics, CDR3 length, and composition were extracted from the output provided by IMGT/High V quest using ARGalaxy. 34 Of each unique clone, the position and frequency of mutations were determined within the IGHV gene (CDR1-FR3). SHM was determined as variations on the best matched V-gene and represented as the percentage of mutations of the total sequenced V-gene nucleotides.…”

Section: Sanger Sequencing Of Igh Gene Rearrangements From Pbmcmentioning

confidence: 99%

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Human IgG2‐ and IgG4‐expressing memory B cells display enhanced molecular and phenotypic signs of maturity and accumulate with age

et al. 2017

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The mechanisms involved in sequential immunoglobulin G (IgG) class switching are still largely unknown. Sequential IG class switching is linked to higher levels of somatic hypermutation (SHM) in vivo, but it remains unclear if these are generated temporally during an immune response or upon activation in a secondary response. We here aimed to uncouple these processes and to distinguish memory B cells from primary and secondary immune responses. SHM levels and IgG subclasses were studied with 454 pyrosequencing on blood mononuclear cells from young children and adults as models for primary and secondary immunological memory. Additional sequencing and detailed immunophenotyping with IgG subclass-specific antibodies was performed on purified IgG+ memory B-cell subsets. In both children and adults, SHM levels were higher in transcripts involving more downstream-located IGHG genes (esp. IGHG2 and IGHG4). In adults, SHM levels were significantly higher than in children, and downstream IGHG genes were more frequently utilized. This was associated with increased frequencies of CD27+IgG+ memory B cells, which contained higher levels of SHM, more IGHG2 usage, and higher expression levels of activation markers than CD27−IgG+ memory B cells. We conclude that secondary immunological memory accumulates with age and these memory B cells express CD27, high levels of activation markers, and carry high SHM levels and frequent usage of IGHG2. These new insights contribute to our understanding of sequential IgG subclass switching and show a potential relevance of using serum IgG2 levels or numbers of IgG2-expressing B cells as markers for efficient generation of memory responses.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Sanger Sequencing Of Igh Gene Rearrangements From Pbmcmentioning

confidence: 99%

Section: Sanger Sequencing Of Igh Gene Rearrangements From Pbmcmentioning

confidence: 99%

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Human IgG2‐ and IgG4‐expressing memory B cells display enhanced molecular and phenotypic signs of maturity and accumulate with age

et al. 2017

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“…Vidjil is also available as a webserver, as is ASAP [1]. Antigen Receptor Galaxy [16] offers online access to many analysis tools. These tools have a subset of the summary statistics described here, and do not have the comparative analysis features of sumrep.…”

Section: Resultsmentioning

confidence: 99%

sumrep: a summary statistic framework for immune receptor repertoire comparison and model validation

Olson

Moghimi

Schramm

et al. 2019

Preprint

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The adaptive immune system generates an incredible diversity of antigen receptors for B and T cells to keep dangerous pathogens at bay. The DNA sequences coding for these receptors arise by a complex recombination process followed by a series of productivity-based filters, as well as affinity maturation for B cells, giving considerable diversity to the circulating pool of receptor sequences. Although these datasets hold considerable promise for medical and public health applications, the complex structure of the resulting adaptive immune receptor repertoire sequencing (AIRR-seq) datasets makes analysis difficult. In this paper we introduce sumrep, an R package that efficiently performs a wide variety of repertoire summaries and comparisons, and show how sumrep can be used to perform model validation. We find that summaries vary in their ability to differentiate between datasets, although many are able to distinguish between covariates such as donor, timepoint, and cell type for BCR and TCR repertoires. We show that deletion and insertion lengths resulting from V(D)J recombination tend to be more discriminative characterizations of a repertoire than summaries that describe the amino acid composition of the CDR3 region. We also find that state-of-the-art generative models excel at recapitulating gene usage and recombination statistics in a given experimental repertoire, but struggle to capture many physiochemical properties of real repertoires.

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IVIg‐induced plasmablasts in patients with Guillain‐Barré syndrome

Brem

Jacobs

Rijs

et al. 2018

Ann Clin Transl Neurol

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ObjectiveThe Guillain–Barré syndrome (GBS) is an acute, immune‐mediated disease of peripheral nerves. Plasmablasts and plasma cells play a central role in GBS by producing neurotoxic antibodies. The standard treatment for GBS is high‐dose intravenous immunoglobulins (IVIg), however the working mechanism is unknown and the response to treatment is highly variable. We aimed to determine whether IVIg changes the frequency of B‐cell subsets in patients with GBS.MethodsPeripheral blood mononuclear cells were isolated from 67 patients with GBS before and/or 1, 2, 4, and 12 weeks after treatment with high‐dose IVIg. B‐cell subset frequencies were determined by flow cytometry and related to serum immunoglobulin levels. Immunoglobulin transcripts before and after IVIg treatment were examined by next‐generation sequencing. Antiglycolipid antibodies were determined by ELISA.ResultsPatients treated with IVIg demonstrated a strong increase in plasmablasts, which peaked 1 week after treatment. Flow cytometry identified a relative increase in IgG2 plasmablasts posttreatment. Within IGG sequences, dominant clones were identified which were also IGG2 and had different immunoglobulin sequences compared to pretreatment samples. High plasmablast frequencies after treatment correlated with an increase in serum IgG and IgM, suggesting endogenous production. Patients with a high number of plasmablasts started to improve earlier (P = 0.015) and were treated with a higher dose of IVIg.InterpretationHigh‐dose IVIg treatment alters the distribution of B‐cell subsets in the peripheral blood of GBS patients, suggesting de novo (oligo‐)clonal B‐cell activation. Very high numbers of plasmablasts after IVIg therapy may be a potential biomarker for fast clinical recovery.

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Antigen Receptor Galaxy: A User-Friendly, Web-Based Tool for Analysis and Visualization of T and B Cell Receptor Repertoire Data

Cited by 44 publications

References 30 publications

Human IgG2‐ and IgG4‐expressing memory B cells display enhanced molecular and phenotypic signs of maturity and accumulate with age

Human IgG2‐ and IgG4‐expressing memory B cells display enhanced molecular and phenotypic signs of maturity and accumulate with age

sumrep: a summary statistic framework for immune receptor repertoire comparison and model validation

IVIg‐induced plasmablasts in patients with Guillain‐Barré syndrome

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