Similarity-based search of model organism, disease and drug effect phenotypes.

Background: Semantic similarity measures over phenotype ontologies have been demonstrated to provide a powerful approach for the analysis of model organism phenotypes, the discovery of animal models of human disease, novel pathways, gene functions, druggable therapeutic targets, and determination of pathogenicity.

Results: We have developed PhenomeNET 2, a system that enables similarity-based searches over a large repository of phenotypes in real-time. It can be used to identify strains of model organisms that are phenotypically similar to human patients, diseases that are phenotypically similar to model organism phenotypes, or drug effect profiles that are similar to the phenotypes observed in a patient or model organism.

Anatomy ontologies and potential users: bridging the gap.

Motivation: To evaluate how well current anatomical ontologies fit the way real-world users apply anatomy terms in their data annotations.

Methods: Annotations from three diverse multi-species public-domain datasets provided a set of use cases for matching anatomical terms in two major anatomical ontologies (the Foundational Model of Anatomy and Uberon), using two lexical-matching applications (Zooma and Ontology Mapper).

Results: Approximately 1500 terms were identified; Uberon/Zooma mappings provided 286 matches, compared to the control and Ontology Mapper returned 319 matches.

The European radiobiological archives: online access to data from radiobiological experiments.

For financial and ethical reasons, the large-scale radiobiological animal studies conducted over the past 50 years are, to a large extent, unrepeatable experiments. It is therefore important to retain the primary data from these experiments to allow reanalysis, reinterpretation and re-evaluation of results from, for example, carcinogenicity studies, in the light of new knowledge in radiation biology. Consequently, there is an imperative need to keep these data available for the research community.

Finding and sharing: new approaches to registries of databases and services for the biomedical sciences.

The recent explosion of biological data and the concomitant proliferation of distributed databases make it challenging for biologists and bioinformaticians to discover the best data resources for their needs, and the most efficient way to access and use them. Despite a rapid acceleration in uptake of syntactic and semantic standards for interoperability, it is still difficult for users to find which databases support the standards and interfaces that they need. To solve these problems, several groups are developing registries of databases that capture key metadata describing the biological scope, utility, accessibility, ease-of-use and existence of web services allowing interoperability between resources.

Mouse Resource Browser--a database of mouse databases.

The laboratory mouse has become the organism of choice for discovering gene function and unravelling pathogenetic mechanisms of human diseases through the application of various functional genomic approaches. The resulting deluge of data has led to the deployment of numerous online resources and the concomitant need for formalized experimental descriptions, data standardization, database interoperability and integration, a need that has yet to be met. We present here the Mouse Resource Browser (MRB), a database of mouse databases that indexes 217 publicly available mouse resources under 22 categories and uses a standardised database description framework (the CASIMIR DDF) to provide information on their controlled vocabularies (ontologies and minimum information standards), and technical information on programmatic access and data availability.

Pathbase and the MPATH ontology. Community resources for mouse histopathology.

Pathbase, the database of mouse histopathology images, was developed as a resource to provide free access to representative images of lesions in background and mutant strains of laboratory mice. When utilized with diagnostic workups or phenotyping of mutant mice, it can provide a "virtual second opinion" for those working without access to groups of experienced pathologists. This is a community resource, and it facilitates the sharing of expertise and data among members of the pathology community worldwide.

Phenotype ontologies for mouse and man: bridging the semantic gap.

A major challenge of the post-genomic era is coding phenotype data from humans and model organisms such as the mouse, to permit the meaningful translation of phenotype descriptions between species. This ability is essential if we are to facilitate phenotype-driven gene function discovery and empower comparative pathobiology. Here, we review the current state of the art for phenotype and disease description in mice and humans, and discuss ways in which the semantic gap between coding systems might be bridged to facilitate the discovery and exploitation of new mouse models of human diseases.

Towards the integration of mouse databases - definition and implementation of solutions to two use-cases in mouse functional genomics.

Background: The integration of information present in many disparate biological databases represents a major challenge in biomedical research. To define the problems and needs, and to explore strategies for database integration in mouse functional genomics, we consulted the biologist user community and implemented solutions to two user-defined use-cases.

Results: We organised workshops, meetings and used a questionnaire to identify the needs of biologist database users in mouse functional genomics.

A data-capture tool for mouse pathology phenotyping.

The Mouse Disease Information System is a free Microsoft Access database (http://research.jax.org/faculty/sundberg/index.

Progress in updating the European Radiobiology Archives.

Purpose: The European Radiobiology Archives (ERA), together with corresponding Japanese and American databases, hold data from nearly all experimental animal radiation biology studies carried out between 1960 and 1998, involving more than 300,000 animals. The Federal Office for Radiation Protection, together with the University of Cambridge have undertaken to transfer the existing ERA archive to a web-based database to maximize its usefulness to the scientific community and bring data coding and structure of this legacy database into congruence with currently accepted semantic standards for anatomy and pathology.

Methods: The accuracy of the primary data input was assessed and improved.

The newsletter 'European Research in Radiological Sciences'.

The newsletter 'European Research in Radiological Sciences' is jointly published by the European Late Effects Project Group and the European Radiation Dosimetry Group to disseminate information about research projects and activities carried out under the EURATOM Framework Programme. Since May 2003, the Newsletter is operated interactively from the Internet. The new site uses a dedicated database that automatically generates HTML pages.

Pathbase: a new reference resource and database for laboratory mouse pathology.

Pathbase (http://www.pathbase.net) is a web accessible database of histopathological images of laboratory mice, developed as a resource for the coding and archiving of data derived from the analysis of mutant or genetically engineered mice and their background strains.

Pathbase: a database of mutant mouse pathology.

Pathbase is a database that stores images of the abnormal histology associated with spontaneous and induced mutations of both embryonic and adult mice including those produced by transgenesis, targeted mutagenesis and chemical mutagenesis. Images of normal mouse histology and strain-dependent background lesions are also available. The database and the images are publicly accessible (http://www.

Recombinant soluble low density lipoprotein receptor fragment inhibits minor group rhinovirus infection in vitro.

A fragment of the low density lipoprotein receptor encompassing the seven ligand binding repeats was expressed in Sf9 insect cells as a fusion protein with a carboxyl-terminally linked hexa-his tag by using a baculovirus vector. Up to 10 mg/l of the fusion protein was secreted into the medium. The material was soluble in the absence of detergent and active in binding beta very low density lipoprotein and a member of the minor group of human rhinoviruses (HRV2) in ligand blots from sodium dodecyl sulfate-polyacrylamide gels run under nonreducing conditions.

Avian homologs of the mammalian low-density lipoprotein receptor family bind minor receptor group human rhinovirus.

Avian oocyte-specific very low density lipoprotein receptor specifically binds human rhinovirus of the minor receptor group on ligand blots and in solution. The solubilized receptor protects cell against infection in a dose-dependent manner.

Members of the low density lipoprotein receptor family mediate cell entry of a minor-group common cold virus.

A protein binding to a minor-group human rhinovirus (HRV2) was purified from HeLa cell culture supernatant. The amino acid sequences of tryptic peptides showed identity with the human low density lipoprotein (LDL) receptor (LDLR). LDL and HRV2 mutually competed for binding sites on human fibroblasts.

Shedding of a rhinovirus minor group binding protein: evidence for a Ca(2+)-dependent process.

Soluble rhinovirus minor group binding activity was found to be shed into the medium upon incubation of HeLa cells at 37 degrees C. Although substantial amounts of this protein were released, no decrease of virus binding to the cell surface was seen. When the membrane-associated receptor was stripped from the cells with trypsin, virus binding was rapidly restored from an intracellular pool even in the absence of de novo protein synthesis.

Stabilization of human rhinovirus serotype 2 against pH-induced conformational change by antiviral compounds.

Four WIN compounds with anti-picornavirus activities were tested for their ability to stabilize human rhinovirus serotype 2 (HRV-2) against low pH-induced conformational changes in vitro, as determined by specific immunoprecipitation. These results were compared to the minimal inhibitory concentration (MIC) as measured in a plaque reduction assay. A direct relationship was observed between the concentration of the compound that prevented the low pH-induced conformational changes and the MIC, indicating that stabilization is an important element in the mode of action of these drugs against HRV-2.