BACKGROUND: Probabilistic functional integrated networks (PFINs) are designed to aid our understanding of cellular biology and can be used to generate testable hypotheses about protein function. PFINs are generally created by scoring the quality of interaction datasets against a Gold Standard dataset, usually chosen from a separate high-quality data source, prior to their integration. Use of an external Gold Standard has several drawbacks, including data redundancy, data loss and the need for identifier mapping, which can complicate the network build and impact on PFIN performance. Additionally, there typically are no Gold Standard data for non-model organisms. RESULTS: We describe the development of an integration technique, ssNet, that scores and integrates both high-throughput and low-throughout data from a single source database in a consistent manner without the need for an external Gold Standard dataset. Using data from Saccharomyces cerevisiae we show that ssNet is easier and faster, overcoming the challenges of data redundancy, Gold Standard bias and ID mapping. In addition ssNet results in less loss of data and produces a more complete network. CONCLUSIONS: The ssNet method allows PFINs to be built successfully from a single database, while producing comparable network performance to networks scored using an external Gold Standard source and with reduced data loss.

MOTIVATION: Biological systems are complex and challenging to model and therefore model reuse is highly desirable. To promote model reuse, models should include both information about the specifics of simulations and the underlying biology in the form of metadata. The availability of computationally tractable metadata is especially important for the effective automated interpretation and processing of models. Metadata are typically represented as machine-readable annotations which enhance programmatic access to information about models. Rule-based languages have emerged as a modelling framework to represent the complexity of biological systems. Annotation approaches have been widely used for reaction-based formalisms such as SBML. However, rule-based languages still lack a rich annotation framework to add semantic information, such as machine-readable descriptions, to the components of a model. RESULTS: We present an annotation framework and guidelines for annotating rule-based models, encoded in the commonly used Kappa and BioNetGen languages. We adapt widely adopted annotation approaches to rule-based models. We initially propose a syntax to store machine-readable annotations and describe a mapping between rule-based modelling entities, such as agents and rules, and their annotations. We then describe an ontology to both annotate these models and capture the information contained therein, and demonstrate annotating these models using examples. Finally, we present a proof of concept tool for extracting annotations from a model that can be queried and analyzed in a uniform way. The uniform representation of the annotations can be used to facilitate the creation, analysis, reuse and visualization of rule-based models. Although examples are given, using specific implementations the proposed techniques can be applied to rule-based models in general. AVAILABILITY AND IMPLEMENTATION: The annotation ontology for rule-based models can be found at http://purl.org/rbm/rbmo The krdf tool and associated executable examples are available at http://purl.org/rbm/rbmo/krdf CONTACT: [email protected] or [email protected].

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.

Many biological systems can be modeled as networks. Hence, network analysis is of increasing importance to systems biology. We describe an evolutionary algorithm for selecting clusters of nodes within a large network based upon network topology together with a measure of the relevance of nodes to a set of independently identified genes of interest. We apply the algorithm to a previously published integrated functional network of yeast genes, using a set of query genes derived from a whole genome screen of yeast strains with a mutation in a telomere uncapping gene. We find that the algorithm identifies biologically plausible clusters of genes which are related to the cell cycle, and which contain interactions not previously identified as potentially important. We conclude that the algorithm is valuable for the querying of complex networks, and the generation of biological hypotheses.

Abstract Summary: 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). Contact: [email protected]; [email protected] Supplementary information: Supplementary data are available at Bioinformatics online.

SUMMARY: BioJava is a mature open-source project that provides a framework for processing of biological data. BioJava contains powerful analysis and statistical routines, tools for parsing common file formats and packages for manipulating sequences and 3D structures. It enables rapid bioinformatics application development in the Java programming language. AVAILABILITY: BioJava is an open-source project distributed under the Lesser GPL (LGPL). BioJava can be downloaded from the BioJava website (http://www.biojava.org). BioJava requires Java 1.5 or higher. All queries should be directed to the BioJava mailing lists. Details are available at http://biojava.org/wiki/BioJava:MailingLists.

BACKGROUND: There has been a dramatic increase in the amount of quantitative data derived from the measurement of changes at different levels of biological complexity during the post-genomic era. However, there are a number of issues associated with the use of computational tools employed for the analysis of such data. For example, computational tools such as R and MATLAB require prior knowledge of their programming languages in order to implement statistical analyses on data. Combining two or more tools in an analysis may also be problematic since data may have to be manually copied and pasted between separate user interfaces for each tool. Furthermore, this transfer of data may require a reconciliation step in order for there to be interoperability between computational tools. RESULTS: Developments in the Taverna workflow system have enabled pipelines to be constructed and enacted for generic and ad hoc analyses of quantitative data. Here, we present an example of such a workflow involving the statistical identification of differentially-expressed genes from microarray data followed by the annotation of their relationships to cellular processes. This workflow makes use of customised maxdBrowse web services, a system that allows Taverna to query and retrieve gene expression data from the maxdLoad2 microarray database. These data are then analysed by R to identify differentially-expressed genes using the Taverna RShell processor which has been developed for invoking this tool when it has been deployed as a service using the RServe library. In addition, the workflow uses Beanshell scripts to reconcile mismatches of data between services as well as to implement a form of user interaction for selecting subsets of microarray data for analysis as part of the workflow execution. A new plugin system in the Taverna software architecture is demonstrated by the use of renderers for displaying PDF files and CSV formatted data within the Taverna workbench. CONCLUSION: Taverna can be used by data analysis experts as a generic tool for composing ad hoc analyses of quantitative data by combining the use of scripts written in the R programming language with tools exposed as services in workflows. When these workflows are shared with colleagues and the wider scientific community, they provide an approach for other scientists wanting to use tools such as R without having to learn the corresponding programming language to analyse their own data.

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.

Abstract Life sciences research is based on individuals, often with diverse skills, assembled into research groups. These groups use their specialist expertise to address scientific problems. The in silico experiments undertaken by these research groups can be represented as workflows involving the co‐ordinated use of analysis programs and information repositories that may be globally distributed. With regards to Grid computing, the requirements relate to the sharing of analysis and information resources rather than sharing computational power. The myGrid project has developed the Taverna Workbench for the composition and execution of workflows for the life sciences community. This experience paper describes lessons learnt during the development of Taverna. A common theme is the importance of understanding how workflows fit into the scientists' experimental context. The lessons reflect an evolving understanding of life scientists' requirements on a workflow environment, which is relevant to other areas of data intensive and exploratory science. Copyright © 2005 John Wiley & Sons, Ltd.

Genome comparison and analysis can reveal the structures and junctions of genome sequences of different species. As more genomes are sequenced, genomic data sources are rapidly increasing such that their analysis is beyond the processing capabilities of most research institutes. The grid is a powerful solution to support large-scale genomic data processing and genome analysis. This paper presents the Microbase project that is developing a grid-based system for genome comparison and analysis, and discusses the first implementation of the system (called MicrobaseLite). MicrobaseLite uses a scalable computing environment to support computationally intensive microbial genome comparison and analysis, employing state-of-the-art technologies of Web services, notification, comparative genomics and parallel computing. Microbase will support not only system-defined genome comparison and analysis but also user-defined, remotely conceived genome analysis.

MOTIVATION: In silico experiments in bioinformatics involve the co-ordinated use of computational tools and information repositories. A growing number of these resources are being made available with programmatic access in the form of Web services. Bioinformatics scientists will need to orchestrate these Web services in workflows as part of their analyses. RESULTS: The Taverna project has developed a tool for the composition and enactment of bioinformatics workflows for the life sciences community. The tool includes a workbench application which provides a graphical user interface for the composition of workflows. These workflows are written in a new language called the simple conceptual unified flow language (Scufl), where by each step within a workflow represents one atomic task. Two examples are used to illustrate the ease by which in silico experiments can be represented as Scufl workflows using the workbench application.

SUMMARY: We have written a fully extensible Java application for visually browsing expression data, and clusters of genes or experimental conditions calculated from that data. The application requires a run-time environment for Java2. AVAILABILITY: http://www. sanger.ac.uk/Users/mrp/java/ExpressionBrowser

SUMMARY: We present a set of Perl modules for the flexible and robust parsing and editing of EMBL/SWISS-PROT databases. AVAILABILITY: The Web page at http://www.sanger.ac. uk/Software/PerlModule/ provides information about downloading the SPEM and PrEMBL modules, and provides links to documentation and example code.