ArticleMolecular immunology2011
Somatic hypermutation targeting is influenced by location within the immunoglobulin V region.
Article in Molecular immunology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 26 citations in OpenAlex.
- Article
- Article
- Deep learning model of somatic hypermutation reveals importance of sequence context beyond hotspot targeting.iScience · 2022Article
- Position-Dependent Differential Targeting of Somatic Hypermutation.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Article
- AID Overlapping and Polη Hotspots Are Key Features of Evolutionary Variation Within the Human Antibody Heavy Chain (IGHV) Genes.Frontiers in immunology · 2020Article
- Survival analysis of DNA mutation motifs with penalized proportional hazards.The annals of applied statistics · 2019Article
- The Bayesian optimist's guide to adaptive immune receptor repertoire analysis.Immunological reviews · 2018Review
- The Versatility of Framework Regions of Chicken VImmune network · 2018Article
- Beyond Hot Spots: Biases in Antibody Somatic Hypermutation and Implications for Vaccine Design.Frontiers in immunology · 2018Review
- Gene-Specific Substitution Profiles Describe the Types and Frequencies of Amino Acid Changes during Antibody Somatic Hypermutation.Frontiers in immunology · 2017Article
- Long-lived antigen-induced IgM plasma cells demonstrate somatic mutations and contribute to long-term protection.Nature communications · 2016Article
- The restricted DH gene reading frame usage in the expressed human antibody repertoire is selected based upon its amino acid content.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
- Models of somatic hypermutation targeting and substitution based on synonymous mutations from high-throughput immunoglobulin sequencing data.Frontiers in immunology · 2013Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
The observed mutation pattern in immunoglobulin (Ig) V genes from peripheral B cells is influenced by several mechanisms, including the targeting of AID to specific DNA motifs, negative selection of B cells unable to express Ig receptor, and positive selection of B cells that carry affinity-increasing mutations. These influences, combined with biased codon usage, produce the well-known pattern of increased replacement mutation frequency in the CDR regions, and decreased replacement frequency in the framework regions. Through the analysis of over 12,000 mutated sequences, we show that the specific location in the V gene also significantly influences mutation accumulation. While this position-specific effect is partially explained by selection, it appears independently of the CDR/FWR structure. To further explore the specific targeting of SHM, we propose a statistical formalism describing the mutation probability of a sequence through the multiplication of independent probabilities. Using this model, we show that C→G (or G→C) mutations are almost as frequent as C→T and G→A mutations, in contrast with C→A (or G→T) mutations, which are as any other mutation. The proposed statistical framework allows us to precisely quantify the effect of V gene position, mutation substitution type, and micro-sequence specificity on the observed mutation pattern.
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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.