ArticleGenome research2021
Individualized VDJ recombination predisposes the available Ig sequence space.
Article in Genome research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 36 citations in OpenAlex.
- Immunoglobulin gene polymorphisms shape the naïve B-cell receptor repertoire; relevance to celiac disease.Genes and immunity · 2026Article
- ClareV: a contrastive learning framework for context-aware TRBV representations in TCR repertoires.Frontiers in immunology · 2026Article
- Simulation of adaptive immune receptors and repertoires with complex immune information to guide the development and benchmarking of AIRR machine learning.Nucleic acids research · 2025Article
- Mathematical Characterization of Private and Public Immune Receptor Sequences.Bulletin of mathematical biology · 2023Article
- IGHV allele similarity clustering improves genotype inference from adaptive immune receptor repertoire sequencing data.Nucleic acids research · 2023Article
- Genetic variation in the immunoglobulin heavy chain locus shapes the human antibody repertoire.Nature communications · 2023Article
- Article
- Human thymopoiesis produces polyspecific CD8eLife · 2023Article
- simAIRR: simulation of adaptive immune repertoires with realistic receptor sequence sharing for benchmarking of immune state prediction methods.GigaScience · 2022Article
- Comparing T cell receptor repertoires using optimal transport.PLoS computational biology · 2022Article
- Reference-based comparison of adaptive immune receptor repertoires.Cell reports methods · 2022Article
- Profiling the baseline performance and limits of machine learning models for adaptive immune receptor repertoire classification.GigaScience · 2022Article
- T cell receptor beta germline variability is revealed by inference from repertoire data.Genome medicine · 2022Article
- Machine Learning Approaches to TCR Repertoire Analysis.Frontiers in immunology · 2022Review
- Echidna: integrated simulations of single-cell immune receptor repertoires and transcriptomes.Bioinformatics advances · 2022Article
- Germline polymorphisms and alternative splicing of human immunoglobulin light chain genes.iScience · 2021Article
- Immunoglobulin germline gene variation and its impact on human disease.Genes and immunity · 2021Review
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- Review
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The process of recombination between variable (V), diversity (D), and joining (J) immunoglobulin (Ig) gene segments determines an individual's naive Ig repertoire and, consequently, (auto)antigen recognition. VDJ recombination follows probabilistic rules that can be modeled statistically. So far, it remains unknown whether VDJ recombination rules differ between individuals. If these rules differed, identical (auto)antigen-specific Ig sequences would be generated with individual-specific probabilities, signifying that the available Ig sequence space is individual specific. We devised a sensitivity-tested distance measure that enables inter-individual comparison of VDJ recombination models. We discovered, accounting for several sources of noise as well as allelic variation in Ig sequencing data, that not only unrelated individuals but also human monozygotic twins and even inbred mice possess statistically distinguishable immunoglobulin recombination models. This suggests that, in addition to genetic, there is also nongenetic modulation of VDJ recombination. We demonstrate that population-wide individualized VDJ recombination can result in orders of magnitude of difference in the probability to generate (auto)antigen-specific Ig sequences. Our findings have implications for immune receptor-based individualized medicine approaches relevant to vaccination, infection, and autoimmunity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.