RNA-based immunoglobulin repertoire sequencing is a new tool for the management of monoclonal gammopathy of renal (kidney) significance.

AbstractThe advent and continual improvement of high-throughput sequencing technologies has made immunoglobulin repertoire sequencing accessible and informative regardless of study species. However, to fully map changes in polyclonal dynamics, precise annotation of these constantly rearranging genes is pivotal. For this reason, data agnostic tools able to learn from presented data are required. Most sequence annotation tools are designed primarily for use with human and mouse antibody sequences which use databases with fixed species lists, applying very specific assumptions which select against unique structural characteristics. We present IgMAT, which utilises a reduced amino acid alphabet, incorporates multiple HMM alignments into a single consensus and enables the incorporation of user defined databases to better represent their species of interest.Availability and implementationIgMAT has been developed as a python module, and is available on GitHub (https://github.com/TPI-Immunogenetics/igmat) for download under GPLv3 license.Supplementary informationModel Breakdowns

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Exploring Human Antimicrobial Antibody Responses on a Single B Cell Level

Clinical and Vaccine Immunology ◽

10.1128/cvi.00544-16 ◽

2017 ◽

Vol 24 (5) ◽

Cited By ~ 4

Author(s):

Daniel Hofmann ◽

Jonathan R. Lai

Keyword(s):

B Cell ◽

Vaccine Design ◽

Antibody Responses ◽

Cell Cloning ◽

Protective Antibody ◽

Functional Activities ◽

Variable Domains ◽

Repertoire Sequencing ◽

Immunoglobulin Repertoire

ABSTRACT Analysis of monoclonal antibodies (MAbs) derived from single B cell cloning has been highly beneficial for antimicrobial immunotherapy, vaccine design, and advancing our understanding of pathogen-triggered effects on the human immunoglobulin repertoire. Sequencing of variable domains of single B cells, and characterization of binding and functional activities of MAbs derived from those sequences, provides in-depth insight not only into sites of susceptibility for antibody-mediated neutralization or opsonization of the pathogen but also into the dynamics of protective antibody evolution during infection. This information can be utilized to rapidly develop novel immunotherapies of completely human origin and provides a roadmap for structure-based vaccine design that aims to elicit similar protective antibody responses. Here, we summarize recent aspects of the single B cell cloning approach.

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Antibody–antigen complex modelling in the era of immunoglobulin repertoire sequencing

Molecular Systems Design & Engineering ◽

10.1039/c9me00034h ◽

2019 ◽

Vol 4 (4) ◽

pp. 679-688 ◽

Cited By ~ 9

Author(s):

Matthew I. J. Raybould ◽

Wing Ki Wong ◽

Charlotte M. Deane

Keyword(s):

High Throughput ◽

Gene Sequencing ◽

Immunoglobulin Gene ◽

Antigen Complex ◽

Repertoire Sequencing ◽

Immunoglobulin Repertoire

This review describes a pipeline to find antigen binders in large immunoglobulin gene sequencing datasetsviahigh-throughput antibody–antigen complex modelling.

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Change-O: a toolkit for analyzing large-scale B cell immunoglobulin repertoire sequencing data: Table 1.

Bioinformatics ◽

10.1093/bioinformatics/btv359 ◽

2015 ◽

Vol 31 (20) ◽

pp. 3356-3358 ◽

Cited By ~ 223

Author(s):

Namita T. Gupta ◽

Jason A. Vander Heiden ◽

Mohamed Uduman ◽

Daniel Gadala-Maria ◽

Gur Yaari ◽

...

Keyword(s):

B Cell ◽

Large Scale ◽

Sequencing Data ◽

Data Table ◽

Repertoire Sequencing ◽

Immunoglobulin Repertoire

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Polymorphisms in immunoglobulin heavy chain variable genes and their upstream regions

10.1101/2020.01.27.921197 ◽

2020 ◽

Author(s):

Ivana Mikocziova ◽

Moriah Gidoni ◽

Ida Lindeman ◽

Ayelet Peres ◽

Omri Snir ◽

...

Keyword(s):

B Cell ◽

Disease Susceptibility ◽

Genomic Variation ◽

B Cell Receptors ◽

Sequencing Data ◽

Repertoire Sequencing ◽

V Region ◽

Immunoglobulin Repertoire ◽

Novel Alleles ◽

High Degree

ABSTRACTGermline variations in immunoglobulin genes influence the repertoire of B cell receptors and antibodies, and such polymorphisms may impact disease susceptibility. However, the knowledge of the genomic variation of the immunoglobulin loci is scarce. Here, we report 25 novel germline IGHV alleles as inferred from rearranged naïve B cell cDNA repertoires of 98 individuals. Thirteen novel alleles were selected for validation, out of which ten were successfully confirmed by targeted amplification and Sanger sequencing of non-B cell DNA. Moreover, we detected a high degree of variability upstream of the V-region in the 5’UTR, leader 1, and leader 2 sequences, and found that identical V-region alleles can differ in upstream sequences. Thus, we have identified a large genetic variation not only in the V-region but also in the upstream sequences of IGHV genes. Our findings challenge current approaches used for annotating immunoglobulin repertoire sequencing data.

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VH1 Family Immunoglobulin Repertoire Sequencing after Allogeneic Hematopoietic Stem Cell Transplantation

PLoS ONE ◽

10.1371/journal.pone.0168096 ◽

2017 ◽

Vol 12 (1) ◽

pp. e0168096 ◽

Cited By ~ 3

Author(s):

Maya K. Sethi ◽

Felicitas Thol ◽

Michael Stadler ◽

Michael Heuser ◽

Arnold Ganser ◽

...

Keyword(s):

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Hematopoietic Stem Cell ◽

Hematopoietic Stem ◽

Repertoire Sequencing ◽

Immunoglobulin Repertoire

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Polymorphisms in human immunoglobulin heavy chain variable genes and their upstream regions

Nucleic Acids Research ◽

10.1093/nar/gkaa310 ◽

2020 ◽

Vol 48 (10) ◽

pp. 5499-5510 ◽

Cited By ~ 2

Author(s):

Ivana Mikocziova ◽

Moriah Gidoni ◽

Ida Lindeman ◽

Ayelet Peres ◽

Omri Snir ◽

...

Keyword(s):

B Cell ◽

Disease Susceptibility ◽

Genomic Variation ◽

Sequencing Data ◽

Repertoire Sequencing ◽

V Region ◽

Immunoglobulin Repertoire ◽

New Perspective ◽

Novel Alleles ◽

High Degree

Abstract Germline variations in immunoglobulin genes influence the repertoire of B cell receptors and antibodies, and such polymorphisms may impact disease susceptibility. However, the knowledge of the genomic variation of the immunoglobulin loci is scarce. Here, we report 25 potential novel germline IGHV alleles as inferred from rearranged naïve B cell cDNA repertoires of 98 individuals. Thirteen novel alleles were selected for validation, out of which ten were successfully confirmed by targeted amplification and Sanger sequencing of non-B cell DNA. Moreover, we detected a high degree of variability upstream of the V-REGION in the 5′UTR, L-PART1 and L-PART2 sequences, and found that identical V-REGION alleles can differ in upstream sequences. Thus, we have identified a large genetic variation not only in the V-REGION but also in the upstream sequences of IGHV genes. Our findings provide a new perspective for annotating immunoglobulin repertoire sequencing data.

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