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Motivation: The rise of high-throughput technologies in the post-genomic era has led to the production of large amounts of biological data. Many of these datasets are freely available on the Internet. Making optimal use of these data is a significant challenge for bioinformaticians. Various strategies for integrating data have been proposed to address this challenge. One of the most promising approaches is the development of semantically rich integrated datasets. Although well suited to computational manipulation, such integrated datasets are typically too large and complex for easy visualization and interactive exploration., Results: We have created an integrated dataset for Saccharomyces cerevisiae using the semantic data integration tool Ondex, and have developed a view-based visualization technique that allows for concise graphical representations of the integrated data. The technique was implemented in a plug-in for Cytoscape, called OndexView. We used OndexView to investigate telomere maintenance in S. cerevisiae., Availability: The Ondex yeast dataset and the OndexView plug-in for Cytoscape are accessible at http://bsu.ncl.ac.uk/ondexview.

Unlabelled: Saint is a web application which provides a lightweight annotation integration environment for quantitative biological models. The system enables modellers to rapidly mark up models with biological information derived from a range of data sources., Availability and Implementation: Saint is freely available for use on the web at http://www.cisban.ac.uk/saint. The web application is implemented in Google Web Toolkit and Tomcat, with all major browsers supported. The Java source code is freely available for download at http://saint-annotate.sourceforge.net. The Saint web server requires an installation of libSBML and has been tested on Linux (32-bit Ubuntu 8.10 and 9.04).

The Functional Genomics Experiment data model (FuGE) has been developed to increase the consistency and efficiency of experimental data modeling in the life sciences, and it has been adopted by a number of high-profile standardization organizations. FuGE can be used: (1) directly, whereby generic modeling constructs are used to represent concepts from specific experimental activities; or (2) as a framework within which method-specific models can be developed. FuGE is both rich and flexible, providing a considerable number of modeling constructs, which can be used in a range of different ways. However, such richness and flexibility also mean that modelers and application developers have choices to make when applying FuGE in a given context. This paper captures emerging best practice in the use of FuGE in the light of the experience of several groups by: (1) proposing guidelines for the use and extension of the FuGE data model; (2) presenting design patterns that reflect recurring requirements in experimental data modeling; and (3) describing a community software tool kit (STK) that supports application development using FuGE. We anticipate that these guidelines will encourage consistent usage of FuGE, and as such, will contribute to the development of convergent data standards in omics research.

The analysis of microbial genome sequences can identify protein families that provide potential drug targets for new antibiotics. With the rapid accumulation of newly sequenced genomes, this analysis has become a computationally intensive and data-intensive problem. This paper describes the development of a Web-service-enabled, component-based, architecture to support the large-scale comparative analysis of complete microbial genome sequences and the subsequent identification of orthologues and protein families (Microbase). The system is coordinated through the use of Web-service-based notifications and integrates distributed computing resources together with genomic databases to realize all-against-all comparisons for a large volume of genome sequences and to present the data in a computationally amenable format through a Web service interface. We demonstrate the use of the system in searching for orthologues and candidate protein families, which ultimately could lead to the identification of potential therapeutic targets.

The selective pattern of muscle involvement is a key feature of muscular dystrophies. Dysferlinopathy is a good model for studying this process since it shows variable muscle involvement that can be highly selective even in individual patients. The transcriptomes of proximal and distal muscles from wildtype C57BL/10 and dysferlin deficient C57BL/10.SJL-Dysf mice at a prepathological stage were assessed using the Affymetrix oligonucleotide-microarray system. We detected significant variation in gene expression between proximal and distal muscle in wildtype mice. Dysferlin defiency, even in the absence of pathological changes, altered this proximal distal difference but with little specific overlap with previous microarray analyses of dysferlinopathy. In conclusion, proximal and distal muscle groups show distinct patterns of gene expression and respond differently to dysferlin deficiency. This has implications for the selection of muscles for future microarray analyses, and also offers new routes for investigating the selectivity of muscle involvement in muscular dystrophies.

We present an ontology for describing genomes, genome comparisons, their evolution and biological function. This ontology will support the development of novel genome comparison algorithms and aid the community in discussing genomic evolution. It provides a framework for communication about comparative genomics, and a basis upon which further automated analysis can be built. The nomenclature defined by the ontology will foster clearer communication between biologists, and also standardize terms used by data publishers in the results of analysis programs. The overriding aim of this ontology is the facilitation of consistent annotation of genomes through computational methods, rather than human annotators. To this end, the ontology includes definitions that support computer analysis and automated transfer of annotations between genomes, rather than relying upon human mediation.

This study examines the relationship between coping style, quality of life (QOL) and psychological distress in a sample of patients with leukaemia and lymphoma. Fifty-one consecutive in-patients, day cases and haematology out-patient attenders entered the study and completed a 10-item self-report questionnaire, the Hospital Anxiety and Depression Scale (HADS), the Mental Adjustment to Cancer Scale (MACS) and the Schedule for the Evaluation of Individual Quality of Life (SEIQOL). Fifty-one percent of patients reached caseness for moderate distress. Fourteen percent of patients reached caseness for severe distress. Twenty-seven percent of patients were identified as having adjusted poorly to their diagnosis having low scores on the Fighting Spirit subscale of the MAC and high scores on the Hopeless/Helpless subscale. There was a significant association between patients who scored highly on the HADS and dissatisfaction with the information provided. Use of a logistic regression model showed that those patients most likely to be suffering from severe psychological distress were those with a worse coping style, measured by MAC. The clinical implications of these findings are discussed.

With increasingly sophisticated chemotherapy regimes being prescribed the quality of life of cancer patients has become a key outcome measure. Little has been reported concerning the experience of patients with haematological malignancy receiving chemotherapy. The objective of this study was to evaluate the clinical usefulness of a novel quality of life measure-the Schedule for the Evaluation of Individual Quality of Life-Direct Weighting (SEIQoL-DW) in a sample of patients with either leukaemia or lymphoma. Fifty-one patients from the haematology clinic and in-patient unit at The Royal Devon and Exeter Hospital completed the SEIQoL-DW; in addition, each patient completed the Hospital Anxiety and Depression Scale (HADS) and a ten item questionnaire covering aspects of their treatment and satisfaction with information provided. The practical application of the SEIQoL-DW is described and two patients quality of life profiles are illustrated for comparison. The relationship between quality of life, satisfaction with information provided and psychological distress as measured by the HADS is discussed., (Copyright 2002 John Wiley & Sons, Ltd.)

Aims: This study sought to examine the risk posed by house mice transmitting pathogens to livestock on typical mixed-agriculture farms in the UK., Methods and Results: In a 10-month longitudinal study at one farm, 222 faecal samples were taken from mice and 57 swabs from the farm environment; 3.2% and 15.8%, respectively, were positive for Yersinia. Seventy-five intestinal samples were taken from house mice from three other farms and 9.3% were positive for Yersinia. The commonest species was Y. enterocolitica (of a wide range of serotypes); all isolates were non-pathogenic, except one of Y. pseudotuberculosis. Salmonella was not isolated from any sample., Conclusion: This study provides additional evidence that house mice are generally not significant vectors of either pathogenic Yersinia strains or Salmonella species., Significance and Impact of the Study: This is the first longitudinal study of Yersinia in any small mammal population, and shows infection to be a dynamic series of generally non-pathogenic, transient infections.

In severe falciparum malaria with high parasitaemia, removal of parasitized erythrocytes is generally considered to be of value as adjunctive therapy in addition to standard chemotherapy. Such removal is commonly achieved by exchange transfusion but this procedure is time-consuming and may be associated with haemodynamic disturbance. Current-generation automated cell-separator hardware and software allows prompt red cell exchange, erythrocytapheresis, in a single continuous-flow isovolaemic procedure. We describe the application of this procedure to 5 cases of severe falciparum malaria in travellers returning to the UK from the tropics. All patients also received quinine and conventional supportive therapy. In all cases, dramatic reduction in parasitaemia was achieved within 2 h with subsequent complete clinical recovery. Erythrocytapheresis has significant advantages over exchange transfusion in terms of speed, efficiency, haemodynamic stability and retention of plasma components such as clotting factors and may thus represent an improvement in adjunctive therapy for severe malaria.

Removal of parasitized erythrocytes is generally considered to be of value as adjunctive therapy in severe falciparum malaria with high parasitaemia. This is commonly achieved by exchange transfusion. We describe three cases of severe falciparum malaria treated by automated erythrocytapheresis (red cell exchange) in addition to quinine and conventional supportive therapy. Erythrocytapheresis consists of removal of the red-cell fraction by apheresis. Plasma, leukocyte and platelet fractions are returned to the patient. In all cases, dramatic reduction in parasitaemia was achieved within 2 h with subsequent complete clinical recovery. Erythrocytapheresis has significant advantages over exchange transfusion in terms of speed, efficiency, haemodynamic stability and retention of plasma components such as clotting factors and may thus represent an improvement in adjunctive therapy for severe malaria.

Red cell exchange is important in the care of acutely ill sickle-cell patients, and may be life-saving. An automated red cell exchange technique has been developed using a Baxter blood cell separator, enabling an isovolaemic exchange to be performed within 2.5 h. A total of 20 procedures have been performed in 15 patients, including one woman in the third trimester of pregnancy, with a mean decrease of 72% in the circulating sickle haemoglobin (HbS) level. This method enables almost all adult patients with sickle cell anaemia to have their HbS reduced to safe levels by only one procedure. The procedure was well tolerated by all patients, including those who were acutely ill. This technique provides an effective procedure for reducing the percentage of circulating HbS rapidly in acutely ill patients with complications of sickle cell anaemia.