IMGT-Choreography for immunogenetics and immunoinformatics.

IMGT, the international ImMunoGeneTics information system (http://imgt.cines.fr), was created in 1989 at Montpellier, France. IMGT is a high quality integrated knowledge resource specialized in immunoglobulins (IG), T cell receptors (TR), major histocompatibility complex (MHC) of human and other vertebrates, and related proteins of the immune system (RPI) which belong to the immunoglobulin superfamily (IgSF) and MHC superfamily (MhcSF). IMGT provides a common access to standardized data from genome, proteome, genetics and three-dimensional structures. The accuracy and the consistency of IMGT data are based on IMGT-ONTOLOGY, a semantic specification of terms to be used in immunogenetics and immunoinformatics. IMGT-ONTOLOGY has been formalized using XML Schema (IMGT-ML) for interoperability with other information systems. We are developing Web services to automatically query IMGT databases and tools. This is the first step towards IMGT-Choreography which will trigger and coordinate dynamic interactions between IMGT Web services to process complex significant biological and clinical requests. IMGT-Choreography will further increase the IMGT leadership in immunogenetics and immunoinformatics for medical research (repertoire analysis of the IG antibody sites and of the TR recognition sites in autoimmune and infectious diseases, AIDS, leukemias, lymphomas, myelomas), veterinary research (IG and TR repertoires in farm and wild life species), genome diversity and genome evolution studies of the adaptive immune responses, biotechnology related to antibody engineering (single chain Fragment variable (scFv), phage displays, combinatorial libraries, chimeric, humanized and human antibodies), diagnostics (detection and follow up of residual diseases) and therapeutical approaches (grafts, immunotherapy, vaccinology). IMGT is freely available at http://imgt.cines.fr.

IMGT, the international ImMunoGeneTics information system.

The international ImMunoGeneTics information system (IMGT) (http://imgt.cines.fr), created in 1989, by the Laboratoire d'ImmunoGenetique Moleculaire LIGM (Universite Montpellier II and CNRS) at Montpellier, France, is a high-quality integrated knowledge resource specializing in the immunoglobulins (IGs), T cell receptors (TRs), major histocompatibility complex (MHC) of human and other vertebrates, and related proteins of the immune systems (RPI) that belong to the immunoglobulin superfamily (IgSF) and to the MHC superfamily (MhcSF). IMGT includes several sequence databases (IMGT/LIGM-DB, IMGT/PRIMER-DB, IMGT/PROTEIN-DB and IMGT/MHC-DB), one genome database (IMGT/GENE-DB) and one three-dimensional (3D) structure database (IMGT/3Dstructure-DB), Web resources comprising 8000 HTML pages (IMGT Marie-Paule page), and interactive tools. IMGT data are expertly annotated according to the rules of the IMGT Scientific chart, based on the IMGT-ONTOLOGY concepts. IMGT tools are particularly useful for the analysis of the IG and TR repertoires in normal physiological and pathological situations. IMGT is used in medical research (autoimmune diseases, infectious diseases, AIDS, leukemias, lymphomas, myelomas), veterinary research, biotechnology related to antibody engineering (phage displays, combinatorial libraries, chimeric, humanized and human antibodies), diagnostics (clonalities, detection and follow up of residual diseases) and therapeutical approaches (graft, immunotherapy and vaccinology). IMGT is freely available at http://imgt.cines.fr.

Mining SAGE data allows large-scale, sensitive screening of antisense transcript expression.

As a growing number of complementary transcripts, susceptible to exert various regulatory functions, are being found in eukaryotes, high throughput analytical methods are needed to investigate their expression in multiple biological samples. Serial Analysis of Gene Expression (SAGE), based on the enumeration of directionally reliable short cDNA sequences (tags), is capable of revealing antisense transcripts. We initially detected them by observing tags that mapped on to the reverse complement of known mRNAs. The presence of such tags in individual SAGE libraries suggested that SAGE datasets contain latent information on antisense transcripts. We raised a collection of virtual tags for mining these data. Tag pairs were assembled by searching for complementarities between 24-nt long sequences centered on the potential SAGE-anchoring sites of well-annotated human expressed sequences. An analysis of their presence in a large collection of published SAGE libraries revealed transcripts expressed at high levels from both strands of two adjacent, oppositely oriented, transcription units. In other cases, the respective transcripts of such cis-oriented genes displayed a mutually exclusive expression pattern or were co-expressed in a small number of libraries. Other tag pairs revealed overlapping transcripts of trans-encoded unique genes. Finally, we isolated a group of tags shared by multiple transcripts. Most of them mapped on to retroelements, essentially represented in humans by Alu sequences inserted in opposite orientations in the 3'UTR of otherwise different mRNAs. Registering these tags in separate files makes possible computational searches focused on unique sense-antisense pairs. The method developed in the present work shows that SAGE datasets constitute a major resource of rapidly investigating with high sensitivity the expression of antisense transcripts, so that a single tag may be detected in one library when screening a large number of biological samples.

A cluster of ten novel MHC class I related genes on human chromosome 6q24.2-q25.3.

We have identified a novel family of human major histocompatibility complex (MHC) class I genes. This MHC class I related gene family is defined by 10 members, among which 6 encode potentially functional glycoproteins. The 180-kb cluster containing them has been generated by serial duplication and minimal diversification of an ancestral prototype. They are not located within the MHC on 6p21.3, but near the tip of its long arm at q24.2-q25.3, close to the human equivalent of the mouse H2-linked t-complex, a subchromosomal region syntenic to a segment of mouse chromosome 10 harboring the orthologous MHC class I related retinoic acid early transcript loci, Raet1a-d. Hence we have named the identified loci RAET1E-N. Human RAET1 products are all devoid of the membrane-proximal immunoglobulin-like alpha3 domain and most, but not all, are predicted to remain membrane-anchored via glycosylphosphatidylinositol linkage and are shown to display an atypical pattern of polymorphism. RAET1 transcripts are absent from hematopoietic tissues, but largely expressed in tumors. The involvement of orthologous mouse RAET1A-D/H60 in natural killer and T-cell activation through NKG2D engagement augurs a similar function for the human RAET1 proteins.