IMPre: An Accurate and Efficient Software for Prediction of T- and B-Cell Receptor Germline Genes and Alleles from Rearranged Repertoire Data

Zhang, Wei; Wang, I‐Ming; Wang, Changxi; Lin, Liya; Chai, Xianghua; Wu, Jinghua; Bett, Andrew J.; Govindarajan, Dhanasekaran; Casimiro, Danilo R.; Liu, Xiao

doi:10.3389/fimmu.2016.00457

Cited by 40 publications

(38 citation statements)

References 20 publications

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“…However, SHM needs to be distinguished from germline alleles present in an individual that are not recorded in a reference database. Germline genes may be inferred from sequencing data (through programmes such as IMPre 126 ), against which SHM may be determined.…”

Section: Box 2 Somatic Hypermutation (Shm)mentioning

confidence: 99%

Antibody repertoire analysis in polygenic autoimmune diseases

2018

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SummaryHigh‐throughput sequencing of the DNA/RNA encoding antibody heavy‐ and light‐chains is rapidly transforming the field of adaptive immunity. It can address key questions, including: (i) how the B‐cell repertoire differs in health and disease; and (ii) if it does differ, the point(s) in B‐cell development at which this occurs. The advent of technologies, such as whole‐genome sequencing, offers the chance to link abnormalities in the B‐cell antibody repertoire to specific genomic variants and polymorphisms. Here, we discuss the current research using B‐cell antibody repertoire sequencing in three polygenic autoimmune diseases where there is good evidence for a pathological role for B‐cells, namely systemic lupus erythematosus, multiple sclerosis and rheumatoid arthritis. These autoimmune diseases exhibit significantly skewed B‐cell receptor repertoires compared with healthy controls. Interestingly, some common repertoire defects are shared between diseases, such as elevated IGHV4‐34 gene usage. B‐cell clones have effectively been characterized and tracked between different tissues and blood in autoimmune disease. It has been hypothesized that these differences may signify differences in B‐cell tolerance; however, the mechanisms and implications of these defects are not clear.

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Section: Box 2 Somatic Hypermutation (Shm)mentioning

confidence: 99%

Antibody repertoire analysis in polygenic autoimmune diseases

2018

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“…When such mismatches are repeatedly seen in a large set of VDJ rearrangements involving multiple IGHJ genes, having diverse CDR3 regions and amplified from a single individual, the inference of a previously undiscovered gene polymorphism may be made with confidence. The discovery of allelic variants by inference is now a feature of most human repertoire studies, and this is facilitated by a number of recently developed utilities 24,25,26,27 (https://arxiv.org/abs/1711.05843). When this approach was applied to the mouse, the outcome was quite unexpected.…”

Section: Introductionmentioning

confidence: 99%

A comparison of immunoglobulin IGHV, IGHD and IGHJ genes in wild-derived and classical inbred mouse strains

Watson

Kos

Gibson

et al. 2019

Preprint

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To better understand the subspecies origin of antibody genes in classical inbred mouse strains, the IGH gene loci of four wild-derived mouse strains were explored by analysis of VDJ gene rearrangements. A total of 341 unique IGHV gene sequences were inferred in the wild-derived strains, including 247 sequences that have not previously been reported. The genes of the Non-Obese Diabetic (NOD) strain were also documented, and all but one of the 84 inferred NOD IGHV genes have previously been observed in C57BL/6 mice. This is surprising because the Swiss mouse-derived NOD strain and the C57BL/6 strain have no known shared ancestry. The relationships between the genes of the wild-derived inbred strains and of the C57BL/6, NOD and BALB/c classical inbred strain were then explored. The IGH loci of the C57BL/6 and the MSM/MsJ strains share many sequences, but analysis showed that few sequences are shared with wild-derived strains representing the three major subspecies of the house mouse. There were also few IGHV sequences that were shared by the BALB/c strain and any of the four wild-derived strains. The origins of IGHV genes in the C57BL/6, MSM/MsJ and BALB/c strains therefore remain unclear. These unexpected similarities and differences highlight our lack of understanding of the antibody gene loci of the laboratory mouse, with implications for the interpretation of strain-specific differences in models of antibody-mediated diseases, and of Adaptive Immune Receptor Repertoire sequencing (AIRR-seq) data. These results also suggest that a position-based immunoglobulin gene nomenclature may be unworkable in the mouse.

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“…The discovery of allelic variants by inference is now a feature of many human repertoire studies, and this is facilitated by a number of recently developed utilities. [22][23][24][25] When this approach was applied to the mouse, the outcome was quite unexpected.…”

Section: Introductionmentioning

confidence: 99%

A comparison of immunoglobulin IGHV, IGHD and IGHJ genes in wild‐derived and classical inbred mouse strains

et al. 2019

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The genomes of classical inbred mouse strains include genes derived from all three major subspecies of the house mouse, Mus musculus. We recently posited that genetic diversity in the immunoglobulin heavy chain (IGH) gene loci of C57BL/6 and BALB/c mice reflects differences in subspecies origin. To investigate this hypothesis, we conducted high‐throughput sequencing of IGH gene rearrangements to document IGH variable (IGHV), joining (IGHJ) and diversity (IGHD) genes in four inbred wild‐derived mouse strains (CAST/EiJ, LEWES/EiJ, MSM/MsJ and PWD/PhJ) and a single disease model strain (NOD/ShiLtJ), collectively representing genetic backgrounds of several major mouse subspecies. A total of 341 germline IGHV sequences were inferred in the wild‐derived strains, including 247 not curated in the international ImMunoGeneTics information system. By contrast, 83/84 inferred NOD IGHV genes had previously been observed in C57BL/6 mice. Variability among the strains examined was observed for only a single IGHJ gene, involving a description of a novel allele. By contrast, unexpected variation was found in the IGHD gene loci, with four previously unreported IGHD gene sequences being documented. Very few IGHV sequences of C57BL/6 and BALB/c mice were shared with strains representing major subspecies, suggesting that their IGH loci may be complex mosaics of genes of disparate origins. This suggests a similar level of diversity is likely present in the IGH loci of other classical inbred strains. This must now be documented if we are to properly understand interstrain variation in models of antibody‐mediated disease.

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IMPre: An Accurate and Efficient Software for Prediction of T- and B-Cell Receptor Germline Genes and Alleles from Rearranged Repertoire Data

Cited by 40 publications

References 20 publications

Antibody repertoire analysis in polygenic autoimmune diseases

Antibody repertoire analysis in polygenic autoimmune diseases

A comparison of immunoglobulin IGHV, IGHD and IGHJ genes in wild-derived and classical inbred mouse strains

A comparison of immunoglobulin IGHV, IGHD and IGHJ genes in wild‐derived and classical inbred mouse strains

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