Abstract
BACKGROUND The number of antigen receptors, immunoglobulins (IG) or antibodies and T cell receptors (TR) of the adaptive immune response in vertebrates with jaws is almost unlimited (2.10 12 per individual in humans). This huge diversity results from complex mechanisms in the synthesis of the variable (V) domains, that include DNA molecular rearrangements of the V, diversity (D) and joining (J) genes, N-diversity at the V-(D)-J junctions and, for IG, somatic hypermutations. The specificity of the V domains is conferred by the complementarity determining regions (CDR) and more particularly the CDR3. IMGT®, the international ImMunoGeneTics information system®, has developed online tools that provide a detailed and accurate sequence analysis of the V domains (IMGT/V-QUEST) and CDR3 (IMGT/JunctionAnalysis), based on IMGT-ONTOLOGY. However online analyses are limited to 50 sequences per batch. The challenge was to provide identical high quality analysis for the huge number of sequences obtained by Next Generation Sequencing (NGS) high throughput and deep sequencing. Results IMGT® has developed IMGT/HighV-QUEST that analyses up to 150,000 IG or TR V domain sequences per batch and performs statistical analysis on the results of up to 450,000 sequences. IMGT/HighV-QUEST provides users with: (i) a friendly web interface for submission and results retrieval, (ii) high quality detailed results of IMGT/V-QUEST and IMGT/JunctionAnalysis, based on the IMGT-ONTOLOGY concepts and IMGT Scientific chart rules, (iii) a standardized frame for NGS statistical analysis, based on ‘Results category’ (‘1 copy’, ‘More than 1’, ‘single allele’, ‘several alleles (or genes)’, (iv) detailed standardized statistical analysis tables and histograms (e.g., V, D and J usage, CDR3-IMGT lengths). Conclusions
Highlights
The number of antigen receptors, immunoglobulins (IG) or antibodies and T cell receptors (TR) of the adaptive immune response in vertebrates with jaws is almost unlimited (2.1012 per individual in humans)
IMGT/HighV-QUEST has been freely available for use for academics on the IMGT® Home page since October 2010
More than 123 million sequences were submitted during its first year
Summary
The number of antigen receptors, immunoglobulins (IG) or antibodies and T cell receptors (TR) of the adaptive immune response in vertebrates with jaws is almost unlimited (2.1012 per individual in humans). This huge diversity results from complex mechanisms in the synthesis of the variable (V) domains, that include DNA molecular rearrangements of the V, diversity (D) and joining (J) genes, N-diversity at the V-(D)-J junctions and, for IG, somatic hypermutations. The potential repertoire of each individual is estimated to comprise about 2.1012 different IG and TR, and the limiting factor is only the number of B and T cells that an organism is genetically programmed to produce [1,2] Concepts were generated that led to the IMGT Scientific chart rules (http://www.imgt.org): standardized keywords (concepts of identification) [12], standardized labels (concepts of description) [13], standardized gene and allele name and nomenclature (concepts of classification) [14], IMGT unique numbering and IMGT Colliers de Perles (concepts of numerotation) [15-
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