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PubMed2004

Towards the automatic generation of biomedical sources schema.

Biologists and physicians need to access biological and medical data for their experimentations and researches. This information is available on the Internet and is scattered over many heterogeneous data sources. Collecting information is consequently tedious, time consuming and must be improved. To cope with this difficulty, our overall objective is to realize a mediator-based system to integrate heterogeneous biomedical data sources. This requires first an automatic generation of source schema, which is the goal of this work. For that, we describe an algorithm which is based on information extraction. It consists of the extraction of meta-information from each source to infer their schema. Our system enables users to access relevant and specific data, which are up-to-date. To solve the semantic heterogeneity of data sources, we are considering the creation of an ontology. Finally, the management of source evolution is discussed

Algorithms↗
PubMed2004

Strategies for supporting consumer health information seeking.

Despite a growing number of available Web-based health information resources, consumers continue to face a variety of barriers as they attempt to access these resources. Developing a system that appropriately responds to user queries poses several challenges. Guided by an earlier study that analyzed a large number of queries submitted to ClinicalTrials.gov, we developed a variety of techniques to assist user information seeking. We tested the efficacy of these techniques by submitting the original user queries to our new search engine to determine if these techniques would result in better system performance. Overall, the number of query failures was reduced, but the largest improvement was found in the system's query suggestion capability. For a subset of query failures, the current system was able to cut the earlier failure rate almost in half, in most cases providing a suggestion rather than directly finding records. The techniques described here provide a new approach for responding to user queries. The techniques are tolerant of certain types of errors and provide feedback to assist users in reformulating their queries.

Abstracting and Indexing↗
PubMed2004

Design, implementation and management of a web-based data entry system for ClinicalTrials.gov.

We describe the development and deployment of a web-based authoring capability, the first implementation of which is used for data entry and management in support of the ClinicalTrials.gov web site. The system facilitates efficient collection of summary protocol information from multiple geographically-dispersed organizations. We explain the motivation for developing this capability, and cite critical design goals. We then describe system design, implementation and operation, focusing on essential aspects of each. We conclude with a summary of the extent to which we met our stated objectives.

Clinical Trials as Topic↗
PubMed2004

New approach for the identification of folate-related pathways in human embryogenesis.

The role of natural folate intake and synthetic folic acid supplementation in the prevention of some congenital malformations is known, but on a molecular biological level poorly understood. In a first approach to identify folate-regulated pathways in human embryogenesis, tryptic digests of Epstein Barr Virus-immortalized B-lymphoblasts proteins from 6 cleft lip and/or palate patients and 2 controls were compared using matrix assisted laser desorption ionisation--time of flight (MALDI-TOF) mass spectrometry. After immortalisation, the lymphoblasts were cultured for 22 days in folate-rich, i.e. 5-methyltetrahydrofolate (5-mTHF), or folate-free medium. On day 22, 5-mTHF was added to the folate-free cultures and the profiles on day 22 and 23 were compared. After background correction for the peptide profiles of the folate-rich cultures, we found in the folate-free mediaseveral differentially expressed peptide peaks upon addition of 5-mTHF. These peptide peaks were mass annotated and matched withthe MSDB human database. The results suggest some folate-regulated protein candidates as Frizzled and the Rho GTP-ases WRCH and Chp that are known in human embryogenesis. Differential folate expressed proteins in patients and controls, however, have to be further investigated.

B-Lymphocytes↗
PubMed2005

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↗
PubMed1996

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1998

"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↗
PubMed1998

Automatic query mapping among genomic databases: a pilot exploration.

As databases in the human genome project proliferate, it is important for users of one genomic database to identify similar or inconsistent data in other autonomously developed genomic databases. To do so, the user needs to issue the same query across multiple databases. We describe an approach that allows a query issued against one database to be automatically mapped to an equivalent query against another structurally different database. Our approach features two components: 1) a database designed to capture knowledge (metadata) that describes the correspondences among individual database components and 2) a module that utilizes the metadata to perform query mappings. As a demonstration, we apply our query mapping approach to two chromosome map databases (DB/12 and GDB).

Algorithms↗