ArticleProceedings of the National Academy of Sciences of the United States of America2015
Automated analysis of high-throughput B-cell sequencing data reveals a high frequency of novel immunoglobulin V gene segment alleles.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 139 papers.
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Who cites it
139 citing papers in PubMed, 228 citations in OpenAlex.
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- An integrated human immunoglobulin germline resource linking allele diversity to expressed repertoire structure.bioRxiv : the preprint server for biology · 2026Article
- Population-level genomic analysis of immunoglobulin loci variation in rhesus macaques reveals extensive germline diversity.Immunity · 2026Article
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- BLIMP1 controls GC B cell expansion and exit through regulating cell cycle progression and key transcription factors BCL6 and IRF4.Cell reports · 2025Article
- Characterization of extensive diversity in immunoglobulin light chain variable germline genes across biomedically important mouse strains.ImmunoHorizons · 2025Article
- Identification of a seasonal influenza vaccine-induced broadly protective neuraminidase antibody.The Journal of experimental medicine · 2025Article
- Towards a sustainable, comprehensive and community-accepted nomenclature and naming standard of antibody and T cell receptor germline genes and alleles.Frontiers in immunology · 2025Article
- Ultrasensitive allele inference from immune repertoire sequencing data with MiXCR.Genome research · 2024Article
- Pathobiont-driven antibody sialylation through IL-10 undermines vaccination.The Journal of clinical investigation · 2024Article
- Defining a highly conserved B cell epitope in the receptor binding motif of SARS-CoV-2 spike glycoprotein.bioRxiv : the preprint server for biology · 2024Article
- An unbiased comparison of immunoglobulin sequence aligners.Briefings in bioinformatics · 2024Article
- Maturation of germinal center B cells after influenza virus vaccination in humans.The Journal of experimental medicine · 2024Article
79 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
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.
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