Patrice Duroux

PHYML Online—a web server for fast maximum likelihood-based phylogenetic inference

PHYML Online is a web interface to PHYML, a software that implements a fast and accurate heuristic for estimating maximum likelihood phylogenies from DNA and protein sequences. This tool provides the user with a number of options, e.g. nonparametric bootstrap and estimation of various evolutionary parameters, in order to perform comprehensive phylogenetic analyses on large datasets in reasonable computing time. The server and its documentation are available at .

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

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/LIGM-DB, the IMGT® comprehensive database of immunoglobulin and T cell receptor nucleotide sequences

IMGT/LIGM-DB is the IMGT® comprehensive database of immunoglobulin (IG) and T cell receptor (TR) nucleotide sequences from human and other vertebrate species. It was created in 1989 by LIGM, Montpellier, France and is the oldest and the largest database of IMGT®. IMGT/LIGM-DB includes all germline (non-rearranged) and rearranged IG and TR genomic DNA (gDNA) and complementary DNA (cDNA) sequences published in generalist databases. IMGT/LIGM-DB allows searches from the Web interface according to biological and immunogenetic criteria through five distinct modules depending on the user interest. For a given entry, nine types of display are available including the IMGT flat file, the translation of the coding regions and the analysis by the IMGT/V-QUEST tool. IMGT/LIGM-DB distributes expertly annotated sequences. The annotations hugely enhance the quality and the accuracy of the distributed detailed information. They include the sequence identification, the gene and allele classification, the constitutive and specific motif description, the codon and amino acid numbering, and the sequence obtaining information, according to the main concepts of IMGT-ONTOLOGY. They represent the main source of IG and TR gene and allele knowledge stored in IMGT/GENE-DB and in the IMGT reference directory. IMGT/LIGM-DB is freely available at .

IMGT®, the international ImMunoGeneTics information system® 25 years on

IMGT®, the international ImMunoGeneTics information system®(http://www.imgt.org) is the global reference in immunogenetics and immunoinformatics. By its creation in 1989 by Marie-Paule Lefranc (Université de Montpellier and CNRS), IMGT® marked the advent of immunoinformatics, which emerged at the interface between immunogenetics and bioinformatics. IMGT® is specialized in the immunoglobulins (IG) or antibodies, T cell receptors (TR), major histocompatibility (MH) and proteins of the IgSF and MhSF superfamilies. IMGT® is built on the IMGT-ONTOLOGY axioms and concepts, which bridged the gap between genes, sequences and 3D structures. The concepts include the IMGT® standardized keywords (identification), IMGT® standardized labels (description), IMGT® standardized nomenclature (classification), IMGT unique numbering and IMGT Colliers de Perles (numerotation). IMGT® comprises 7 databases, 17 online tools and 15 000 pages of web resources, and provides a high-quality and integrated system for analysis of the genomic and expressed IG and TR repertoire of the adaptive immune responses, including NGS high-throughput data. Tools and databases are used in basic, veterinary and medical research, in clinical applications (mutation analysis in leukemia and lymphoma) and in antibody engineering and humanization. The IMGT/mAb-DB interface was developed for therapeutic antibodies and fusion proteins for immunological applications (FPIA). IMGT® is freely available at http://www.imgt.org.

IMGT/HighV QUEST paradigm for T cell receptor IMGT clonotype diversity and next generation repertoire immunoprofiling.

T cell repertoire diversity and clonotype follow-up in vaccination, cancer, infectious and immune diseases represent a major challenge owing to the enormous complexity of the data generated. Here we describe a next generation methodology, which combines 5′RACE PCR, 454 sequencing and, for analysis, IMGT, the international ImMunoGeneTics information system (IMGT), IMGT/HighV-QUEST web portal and IMGT-ONTOLOGY concepts. The approach is validated in a human case study of T cell receptor beta (TRB) repertoire, by chronologically tracking the effects of influenza vaccination on conventional and regulatory T cell subpopulations. The IMGT/HighV-QUEST paradigm defines standards for genotype/haplotype analysis and characterization of IMGT clonotypes for clonal diversity and expression and achieves a degree of resolution for next generation sequencing verifiable by the user at the sequence level, while providing a normalized reference immunoprofile for human TRB.

ImmunoGrid, an integrative environment for large-scale simulation of the immune system for vaccine discovery, design and optimization

Vaccine research is a combinatorial science requiring computational analysis of vaccine components, formulations and optimization. We have developed a framework that combines computational tools for the study of immune function and vaccine development. This framework, named ImmunoGrid combines conceptual models of the immune system, models of antigen processing and presentation, system-level models of the immune system, Grid computing, and database technology to facilitate discovery, formulation and optimization of vaccines. ImmunoGrid modules share common conceptual models and ontologies. The ImmunoGrid portal offers access to educational simulators where previously defined cases can be displayed, and to research simulators that allow the development of new, or tuning of existing, computational models. The portal is accessible at .

ImmunoGrid: towards agent-based simulations of the human immune system at a natural scale †

The ultimate aim of the EU-funded ImmunoGrid project is to develop a natural-scale model of the human immune system—that is, one that reflects both the diversity and the relative proportions of the molecules and cells that comprise it—together with the grid infrastructure necessary to apply this model to specific applications in the field of immunology. These objectives present the ImmunoGrid Consortium with formidable challenges in terms of complexity of the immune system, our partial understanding about how the immune system works, the lack of reliable data and the scale of computational resources required. In this paper, we explain the key challenges and the approaches adopted to overcome them. We also consider wider implications for the present ambitious plans to develop natural-scale, integrated models of the human body that can make contributions to personalized health care, such as the European Virtual Physiological Human initiative. Finally, we ask a key question: How long will it take us to resolve these challenges and when can we expect to have fully functional models that will deliver health-care benefits in the form of personalized care solutions and improved disease prevention?

dbaasp: database of antimicrobial activity and structure of peptides

The Database of Antimicrobial Activity and Structure of Peptides (DBAASP) is a manually curated database for those peptides for which antimicrobial activity against particular targets has been evaluated experimentally. The database is a depository of complete information on: the chemical structure of peptides; target species; target object of cell; peptide antimicrobial/haemolytic/cytotoxic activities; and experimental conditions at which activities were estimated. The DBAASP search page allows the user to search peptides according to their structural characteristics, complexity type (monomer, dimer and two-peptide), source, synthesis type (ribosomal, nonribosomal and synthetic) and target species. The database prediction algorithm provides a tool for rational design of new antimicrobial peptides. DBAASP is accessible at http://www.biomedicine.org.ge/dbaasp/.

IMGT/Collier de Perles: IMGT Standardized Representation of Domains (IG, TR, and IgSF Variable and Constant Domains, MH and MhSF Groove Domains)

Cold Spring Harb Protoc; François Ehrenmann, Véronique Giudicelli, Patrice Duroux and Marie-Paule Lefranc and IgSF Variable and Constant Domains, MH and MhSF Groove Domains) IMGT/Collier de Perles: IMGT Standardized Representation of Domains (IG, TR, Service Email Alerting click here. Receive free email alerts when new articles cite this article Categories Subject Cold Spring Harbor Protocols. Browse articles on similar topics from (28 articles) Sequence Database Searching (15 articles) Phylogenetic Prediction (89 articles) Immunology, general (322 articles) Genetics, general (74 articles) Computational Biology (167 articles) Characterization of Proteins (131 articles) Bioinformatics/Genomics, general (33 articles) Alignment of Sequences

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

IMGT(®), the international ImMunoGeneTics information system(®) (http://www.imgt.org), was created in 1989 to manage the huge diversity of the antigen receptors, immunoglobulins (IG) or antibodies, and T cell receptors (TR). Standardized sequence and structure analysis of antibody using IMGT(®) databases and tools allows 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 Colliers de Perles). IMGT(®) is the international reference for immunogenetics and immunoinformatics and its standards are particularly useful for antibody humanization and evaluation of immunogenicity. IMGT(®) databases for antibody nucleotide sequences and genes include IMGT/LIGM-DB and IMGT/GENE-DB, respectively, whereas nucleotide sequence analysis is performed by the IMGT/V-QUEST, IMGT/HighV-QUEST, and IMGT/JunctionAnalysis tools. 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, the IMGT/2Dstructure-DB database for amino acid sequences of monoclonal antibodies (mAb, suffix -mab) and fusion proteins for immune applications (FPIA, suffix -cept) of the World Health Organization/International Nonproprietary Name (WHO/INN) programme and other proteins of interest, and the IMGT/3Dstructure-DB database for crystallized antibodies and its associated tools (IMGT/StructuralQuery, IMGT/DomainSuperimpose).