Showing papers by "Véronique Giudicelli published in 2012"

IMGT(®) tools for the nucleotide analysis of immunoglobulin (IG) and T cell receptor (TR) V-(D)-J repertoires, polymorphisms, and IG mutations: IMGT/V-QUEST and IMGT/HighV-QUEST for NGS.

Abstract: IMGT/V-QUEST is the highly customized and integrated online IMGT(®) tool for the standardized analysis of the immunoglobulin (IG) or antibody and T cell receptor (TR) rearranged nucleotide sequences. The analysis of these antigen receptors represents a crucial challenge for the study of the adaptive immune response in normal and disease-related situations. The expressed IG and TR repertoires represent a potential of 10(12) IG and 10(12) TR per individual. This huge diversity results from mechanisms that occur at the DNA level during the IG and TR molecular synthesis. These mechanisms include the combinatorial rearrangements of the variable (V), diversity (D) and joining (J) genes, the N-diversity (deletion and addition at random of nucleotides during the V-(D)-J rearrangement) and, for IG, somatic hypermutations. IMGT/V-QUEST identifies the V, D, J genes and alleles by alignment with the germline IG and TR gene and allele sequences of the IMGT reference directory. The tool describes the V-REGION mutations and identifies the hot spot positions in the closest germline V gene. IMGT/V-QUEST integrates IMGT/JunctionAnalysis for a detailed analysis of the V-J and V-D-J junctions and IMGT/Automat for a complete annotation of the sequences and also provides IMGT Collier de Perles. IMGT/HighV-QUEST, the high-throughput version of IMGT/V-QUEST, implemented to answer the needs of deep sequencing data analysis from Next Generation Sequencing (NGS), allows the analysis of thousands of IG and TR sequences in a single run. IMGT/V-QUEST and IMGT/HighV-QUEST are available at the IMGT(®) Home page, http://www.imgt.org.

Imgt/highv-quest: the imgt® web portal for immunoglobulin (ig) or antibody and t cell receptor (tr) analysis from ngs high throughput and deep sequencing

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

Antigen receptor stereotypy across B-cell lymphoproliferations: the case of IGHV4-59/IGKV3-20 receptors with rheumatoid factor activity.

Abstract: Antigen receptor stereotypy across B-cell lymphoproliferations: the case of IGHV4-59/IGKV3-20 receptors with rheumatoid factor activity

Use of IMGT(®) databases and tools for antibody engineering and humanization.

Abstract: IMGT®, the international ImMunoGeneTics information system® ( http://www.imgt.org ), was created in 1989 by Marie-Paule Lefranc (Universite de Montpellier and CNRS) to manage the huge diversity of the antigen receptors, immunoglobulins (IG) or antibodies, and T cell receptors (TR). The founding of IMGT® marked the advent of immunoinformatics, which emerged at the interface between immunogenetics and bioinformatics. Standardized sequence and structure analysis of antibody using IMGT® databases and tools allow one to bridge, for the first time, the gap between antibody sequences and three-dimensional (3D) structures. This is achieved through the IMGT Scientific chart rules, based on the IMGT-ONTOLOGY concepts of classification (IMGT gene and allele nomenclature), description (IMGT standardized labels), and numerotation (IMGT unique numbering and IMGT Collier de Perles). IMGT® is acknowledged as the global reference for immunogenetics and immunoinformatics, and its standards are particularly useful for antibody engineering and humanization. IMGT® databases for antibody nucleotide sequences and genes include IMGT/LIGM-DB and IMGT/GENE-DB, respectively, and nucleotide sequence analysis is performed by the IMGT/V-QUEST and IMGT/JunctionAnalysis tools and for NGS by IMGT/HighV-QUEST. In this chapter, we focus on IMGT® databases and tools for amino acid sequences, two-dimensional (2D) and three-dimensional (3D) structures: the IMGT/DomainGapAlign and IMGT Collier de Perles tools and the IMGT/2Dstructure-DB and IMGT/3Dstructure-DB database. IMGT/mAb-DB provides the query interface for monoclonal antibodies (mAb), fusion proteins for immune applications (FPIA), and composite proteins for clinical applications (CPCA) and related proteins of interest (RPI) and links to the proposed and recommended lists of the World Health Organization International Nonproprietary Name (WHO INN) programme, to IMGT/2Dstructure-DB for amino acid sequences, and to IMGT/3Dstructure-DB and its associated tools (IMGT/StructuralQuery, IMGT/DomainSuperimpose) for crystallized antibodies.

Imgt-ontology 2012.

Abstract: Immunogenetics is the science that studies the genetics of the immune system and immune responses. Owing to the complexity and diversity of the immune repertoire, immunogenetics represents one of the greatest challenges for data interpretation: a large biological expertise, a considerable effort of standardization and the elaboration of an efficient system for the management of the related knowledge were required. IMGT®, the international ImMunoGeneTics information system® (http://www.imgt.org) has reached that goal through the building of a unique ontology, IMGT-ONTOLOGY, which represents the first ontology for the formal representation of knowledge in immunogenetics and immunoinformatics. IMGT-ONTOLOGY manages the immunogenetics knowledge through diverse facets that rely on the seven axioms of the Formal IMGT-ONTOLOGY or IMGT-Kaleidoscope: "IDENTIFICATION", "DESCRIPTION", "CLASSIFICATION", "NUMEROTATION", "LOCALIZATION", "ORIENTATION" and "OBTENTION". The concepts of identification, description, classification and numerotation generated from the axioms led to the elaboration of the IMGT® standards that constitute the IMGT Scientific chart: IMGT® standardized keywords (concepts of identification), IMGT® standardized labels (concepts of description), IMGT® standardized gene and allele nomenclature (concepts of classification) and IMGT unique numbering and IMGT Collier de Perles (concepts of numerotation). IMGT-ONTOLOGY has become the global reference in immunogenetics and immunoinformatics for the knowledge representation of immunoglobulins (IG) or antibodies, T cell receptors (TR) and major histocompatibility (MH) proteins of humans and other vertebrates, proteins of the immunoglobulin superfamily (IgSF) and MH superfamily (MhSF), related proteins of the immune system (RPI) of vertebrates and invertebrates, therapeutic monoclonal antibodies (mAbs), fusion proteins for immune applications (FPIA) and composite proteins for clinical application (CPCA).