VBASE2, an integrative V gene database

Retter, Ida

doi:10.1093/nar/gki088

Cited by 166 publications

(129 citation statements)

References 8 publications

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“…Eleven putative novel alleles (Table 2) were identified by applying the regression-based approach and filtering (described above) to the Ig sequencing data from seven subjects listed in Table 1. These alleles were missing from the IMGT database, and were also not present in VBASE2 (22) or the UNSWIg human heavy chain repertoire (23). Excluded from Table 2 are six alleles that were sequencing artifacts (further discussed in SI Text), and which were eventually removed by the genotyping process described later.…”

Section: Automated Methods Detects Novel Ighv Alleles From Experimentalmentioning

confidence: 99%

“…However, recent studies have discovered the presence of numerous V segments and alleles not reported in any published databases (6,(19)(20)(21), as well as a several novel D and J alleles (19). Some of these V alleles have been incorporated into the IMGT database or alternative databases of germline alleles [such as VBASE2 (22) or the UNSWIg human heavy chain repertoire (23)]. The completeness of the germline V(D)J database may greatly influence downstream analysis results, including clinically relevant decision processes (24), as unreported alleles can skew estimated segment distributions and because novel polymorphisms will appear as recurrent somatic mutations.…”

Section: Significancementioning

confidence: 99%

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Automated analysis of high-throughput B-cell sequencing data reveals a high frequency of novel immunoglobulin V gene segment alleles

Gadala-Maria

Yaari

Uduman³

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

212

250

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Individual variation in germline and expressed B-cell immunoglobulin (Ig) repertoires has been associated with aging, disease susceptibility, and differential response to infection and vaccination. Repertoire properties can now be studied at large-scale through next-generation sequencing of rearranged Ig genes. Accurate analysis of these repertoire-sequencing (Rep-Seq) data requires identifying the germline variable (V), diversity (D), and joining (J) gene segments used by each Ig sequence. Current V(D)J assignment methods work by aligning sequences to a database of known germline V(D)J segment alleles. However, existing databases are likely to be incomplete and novel polymorphisms are hard to differentiate from the frequent occurrence of somatic hypermutations in Ig sequences. Here we develop a Tool for Ig Genotype Elucidation via Rep-Seq (TIgGER). TIgGER analyzes mutation patterns in Rep-Seq data to identify novel V segment alleles, and also constructs a personalized germline database containing the specific set of alleles carried by a subject. This information is then used to improve the initial V segment assignments from existing tools, like IMGT/HighV-QUEST. The application of TIgGER to Rep-Seq data from seven subjects identified 11 novel V segment alleles, including at least one in every subject examined. These novel alleles constituted 13% of the total number of unique alleles in these subjects, and impacted 3% of V(D)J segment assignments. These results reinforce the highly polymorphic nature of human Ig V genes, and suggest that many novel alleles remain to be discovered. The integration of TIgGER into Rep-Seq processing pipelines will increase the accuracy of V segment assignments, thus improving B-cell repertoire analyses.next-generation sequencing | B-cell repertoire | adaptive immunity | somatic hypermutation | variable gene segment T he production by B cells of immunoglobulin (Ig) proteins, which are expressed on the cell surface as B-cell receptors and secreted by subsets of B cells as antibodies, is a key component of the adaptive immune system in humans. Through their specific binding to an enormously diverse range of foreign bodies, Ig proteins are able to elicit further immunological response and provide protection. These proteins are assembled in B cells from two pairs of polypeptide chains, termed heavy and light. The antigen-binding portions of these genes are created through the somatic recombination of gene segments, termed variable (V), diversity (D), and joining (J). During the recombination process, one each of the ∼46 V, 23 D, and 6 J gene segments (1) recombine to make the antigen-binding region of the heavy chain; the light chain is created by a similar process, although involving one of two different loci (λ and κ) containing V and J genes only. Over three million different Ig sequences can be created through this V(D)J recombinatorial process alone (2). The potential diversity of these sequences is further expanded to the order of trillions (2) when combined with the random insert...

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Section: Automated Methods Detects Novel Ighv Alleles From Experimentalmentioning

confidence: 99%

Section: Significancementioning

confidence: 99%

Automated analysis of high-throughput B-cell sequencing data reveals a high frequency of novel immunoglobulin V gene segment alleles

Gadala-Maria

Yaari

Uduman³

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

212

250

View full text Add to dashboard Cite

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“…The D and J H gene segments were identified using FUZZNUC software to search for heptamerenonamer like motifs. The V gene segments were detected by a BLAST search of the BAC sequence in combination with a procedure developed for the automatic generation of the database VBASE2 [34], and with manual sequence analyses. The positions and exon boundaries of IgH C domains were determined …”

Section: Screening Of Bac Library and Annotation Of Igh Gene Locusmentioning

confidence: 99%

Ig heavy chain genes and their locus in grass carp Ctenopharyngodon idella

Xiao

Wang

Yan

et al. 2010

Fish & Shellfish Immunology

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“…In case 1, sequence analysis was performed on RNA extracted from peripheral blood mononuclear cells. In order to determine the level of somatic mutation, patients' sequences were aligned to the germline sequences in the V-BASE 2 database (Retter et al, 2005). The IGHV mutation status was designated as unmutated if there were fewer than 2% mutations (>98% homology to germline sequences), or as mutated if there were 2% or more mutations (£98% homology to germline sequences) compared to the germ-line sequences (Fais et al, 1998).…”

Section: Sequence Analysis Of the Ighv Genesmentioning

confidence: 99%

MYC translocation in chronic lymphocytic leukaemia is associated with increased prolymphocytes and a poor prognosis

Huh¹,

Lin²,

Vega³

et al. 2008

Br J Haematol

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SummaryChromosomal translocations that involve MYC, characteristic of Burkitt lymphoma, are rare in chronic lymphocytic leukaemia (CLL). We report the clinical, morphological, immunophenotypic, cytogenetic and molecular genetic features of eight CLL cases with MYC rearrangement. The patients, five men and three women (median age, 71 years) had bone marrow involvement and an absolute peripheral blood lymphocytosis; five had lymphadenopathy; seven had splenomegaly. Prolymphocytes were increased (≥10%) in all cases. Six cases were classified as CLL with increased prolymphocytes (CLL/PL; prolymphocytes 10–55%), and two were classified as CLL in prolymphocytic transformation (CLL/PT; prolymphocytes >55%). All cases co‐expressed CD5, CD19, and CD23; five of eight expressed ZAP‐70. Of seven cases tested, four had mutated and three had unmutated IGHV genes. Conventional cytogenetic studies demonstrated t(8;14)(q24·1;q32) in five cases, t(8;22)(q24·1;q11) in two cases, and t(2;8)(p12;q24·1) in one case. Seven cases contained additional chromosomal abnormalities. All patients received combination chemotherapy. Two developed Epstein–Barr virus (EBV)‐associated diffuse large B‐cell lymphomas (DLBCL) that were clonally unrelated to the CLL. At follow‐up, two patients are alive, four died of underlying disease, one died of EBV‐associated DLBCL, and one died of an unrelated cancer. In summary, MYC rearrangement, which occurs rarely in CLL patients, is associated with increased prolymphocytes, complex cytogenetic abnormalities, and a poor prognosis.

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VBASE2, an integrative V gene database

Cited by 166 publications

References 8 publications

Automated analysis of high-throughput B-cell sequencing data reveals a high frequency of novel immunoglobulin V gene segment alleles

Automated analysis of high-throughput B-cell sequencing data reveals a high frequency of novel immunoglobulin V gene segment alleles

Ig heavy chain genes and their locus in grass carp Ctenopharyngodon idella

MYC translocation in chronic lymphocytic leukaemia is associated with increased prolymphocytes and a poor prognosis

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