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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.

Alleles↗

Development of grid frameworks for clinical trials and epidemiological studies.

E-Health initiatives such as electronic clinical trials and epidemiological studies require access to and usage of a range of both clinical and other data sets. Such data sets are typically only available over many heterogeneous domains where a plethora of often legacy based or in-house/bespoke IT solutions exist. Considerable efforts and investments are being made across the UK to upgrade the IT infrastructures across the National Health Service (NHS) such as the National Program for IT in the NHS (NPFIT) [1]. However, it is the case that currently independent and largely non-interoperable IT solutions exist across hospitals, trusts, disease registries and GP practices - this includes security as well as more general compute and data infrastructures. Grid technology allows issues of distribution and heterogeneity to be overcome, however the clinical trials domain places special demands on security and data which hitherto the Grid community have not satisfactorily addressed. These challenges are often common across many studies and trials hence the development of a re-usable framework for creation and subsequent management of such infrastructures is highly desirable. In this paper we present the challenges in developing such a framework and outline initial scenarios and prototypes developed within the MRC funded Virtual Organisations for Trials and Epidemiological Studies (VOTES) project [2].

Access to Information↗

[More paper--less research?].

Since the implementation of EU directive 2001/20/EF in May 2004, clinical research has become increasingly complicated to perform. The legal requirements are extensive with the result that clinical researchers find themselves spending more and more time on administrative procedures. The consequences will probably be that the amount of research will decline as a result of the new laws. We describe what the basic requirements for clinical researchers are today.

Biomedical Research↗

List update processing (LUP)--solving the sequence database update problem.

Sequence databases of today require frequent updating. Mirror procedures to copy incrementally updated databases as cumulative sets are the preferred method and can be implemented by straightforward scripting. However, limited bandwidth of networks and the increase of data require more powerful paradigms to reduce the workload reliably. We suggest the List Update Processing (LUP) principle. The system has been implemented on an experimental basis to update the Swiss EMBnet Node (BioComputing Basel, CH) with data from the European Bioinformatics Institute (EMBL Outstation, Hinxton Hall, UK). The results obtained from the prototype suggest to expand the system to several sites.

CD-ROM↗

Ubiquitous distributed objects with CORBA.

Database interoperation is becoming a bottleneck for the research community in biology. In this paper, we first discuss the question of interoperability and give a brief overview of CORBA. Then, an example is explained in some detail: a simple but realistic data bank of STSs is implemented. The Object Request Broker is the media for communication between an object server (the data bank) and a client (possibly a genome center). Since CORBA enables easy development of networked applications, we meant this paper to provide an incentive for the bioinformatics community to develop distributed objects.

Base Sequence↗

An approach to detection of protein structural motifs using an encoding scheme of backbone conformations.

This paper presents an approach to detection of protein structural motifs. In our approach, first all protein backbone conformations are converted into character strings using an encoding scheme. Then we use the Smith-Waterman local alignment algorithm to detect common structural motifs. By comparing results with the PROSITE regular expression patterns, our method can detect several motifs which the PROSITE patterns fail to detect.

Amino Acid Sequence↗

Using the radial distributions of physical features to compare amino acid environments and align amino acid sequences.

We have performed a comprehensive analysis of the microenvironments surrounding the twenty amino acids. Our analysis includes comparison of amino acid environments with random control environments as well as with each of the other amino acid environments. We describe the amino acid environments with a set of 21 features summarizing atomic, chemical group, residue, and secondary structural features. The environments are divided into radial shells of 1 A thickness to represent the distance of the features from the amino acid C beta atoms. We make the results of our analysis available graphically over the world wide web. To illustrate the validity and utility of our analysis, we used the amino acid comparative profiles to construct a substitution matrix, the WAC matrix, based on a simple summary of the computed environmental differences. We compared our matrix to BLOSUM62 and PAM250 in BLAST searches with query sequences selected from 39 protein families found in the PROSITE database. Although BLOSUM62 was the most sensitive matrix overall, our matrix was more sensitive for some families, and exhibited overall performance similar to PAM250. Our results suggest that the radial distribution of biochemical and biophysical features is useful for comparing amino acid environments, and that similarity matrices based on the geometric distribution of features around amino acids may produce improved search sensitivity.

Amino Acid Sequence↗

"Virtual" clinical trials: case control experiments utilizing a health services research workstation.

We created an interface to a growing repository of clinical and administrative information to facilitate the design and execution of case-control experiments. The system enables knowledgeable users to generate and test hypotheses regarding associations among diseases and outcomes. The intuitive interface allows the user to specify criteria for selecting cases and defining putative risks. The repository contains comprehensive administrative and selected clinical information on all ambulatory and emergency department visits as well as hospital admissions since 1994. We tested the workstation's ability to determine relationships between outpatient diagnoses including hypertension, osteoarthritis and hypercholesterolemia with the occurrence of admissions for stroke and myocardial infarction and achieved results consistent with published studies. Successful implementation of this Health Services Research Workstation will allow "virtual" clinical trials to validate the results of formal clinical trials on a local population and may provide meaningful analyses of data when formal clinical trials are not feasible.

Case-Control Studies↗