OBIYagns: a grid-based biochemical simulator with a parameter estimator

SUMMARY: OBIYagns (yet another gene network simulator) is a biochemical system simulator that comprises a multiple-user Web-based graphical interface, an ordinary differential equation solver and a parameter estimators distributed over an open bioinformatics grid (OBIGrid). This grid-based biochemical simulation system can achieve high performance and provide a secure simulation environment for estimating kinetic parameters in an acceptable time period. OBIYagns can be applied to larger system biology-oriented simulation projects. AVAILABILITY: OBIYagns example models, methods and user guide are available at https://access.obigrid.org/yagns/ SUPPLEMENTARY INFORMATION: Please refer to Bioinformatics online.     

The Physiome Model Repository 2

MOTIVATION: The Physiome Model Repository 2 (PMR2) software was created as part of the IUPS Physiome Project (Hunter and Borg, 2003), and today it serves as the foundation for the CellML model repository. Key advantages brought to the end user by PMR2 include: facilities for model exchange, enhanced collaboration and a detailed change history for each model. AVAILABILITY: PMR2 is available under an open source license at http://www.cellml.org/tools/pmr/; a fully functional instance of this software can be accessed at http://models.physiomeproject.org/.     

Tav4SB: integrating tools for analysis of kinetic models of biological systems

ABSTRACT: BACKGROUND: Progress in the modeling of biological systems strongly relies on the availability of specialized computer-aided tools. To that end, the Taverna Workbench eases integration of software tools for life science research and provides a common workflow-based framework for computational experiments in Biology. RESULTS: The Taverna services for Systems Biology (Tav4SB) project provides a set of new Web service operations, which extend the functionality of the Taverna Workbench in a domain of systems biology. Tav4SB operations allow you to perform numerical simulations or model checking of, respectively, deterministic or stochastic semantics of biological models. On top of this functionality, Tav4SB enables the construction of high-level experiments. As an illustration of possibilities offered by our project we apply the multi-parameter sensitivity analysis. To visualize the results of model analysis a flexible plotting operation is provided as well. Tav4SB operations are executed in a simple grid environment, integrating heterogeneous software such as Mathematica, PRISM and SBML ODE Solver. The user guide, contact information, full documentation of available Web service operations, workflows and other additional resources can be found at the Tav4SB project's Web page: http://bioputer.mimuw.edu.pl/tav4sb/. CONCLUSIONS: The Tav4SB Web service provides a set of integrated tools in the domain for which Web-based applications are still not as widely available as for other areas of computational biology. Moreover, we extend the dedicated hardware base for computationally expensive task of simulating cellular models. Finally, we promote the standardization of models and experiments as well as accessibility and usability of remote services.     

Rintact: enabling computational analysis of molecular interaction data from the IntAct repository

MOTIVATION: The IntAct repository is one of the largest and most widely used databases for the curation and storage of molecular interaction data. These datasets need to be analyzed by computational methods. Software packages in the statistical environment R provide powerful tools for conducting such analyses. RESULTS: We introduce Rintact, a Bioconductor package that allows users to transform PSI-MI XML2.5 interaction data files from IntAct into R graph objects. On these, they can use methods from R and Bioconductor for a variety of tasks: determining cohesive subgraphs, computing summary statistics, fitting mathematical models to the data or rendering graphical layouts. Rintact provides a programmatic interface to the IntAct repository and allows the use of the analytic methods provided by R and Bioconductor. AVAILABILITY: Rintact is freely available at http://bioconductor.org     

Intervertebral reaction force prediction using an enhanced assembly of OpenSim models

OpenSim offers a valuable approach to investigating otherwise difficult to assess yet important biomechanical parameters such as joint reaction forces. Although the range of available models in the public repository is continually increasing, there currently exists no OpenSim model for the computation of intervertebral joint reactions during flexion and lifting tasks. The current work combines and improves elements of existing models to develop an enhanced model of the upper body and lumbar spine. Models of the upper body with extremities, neck and head were combined with an improved version of a lumbar spine from the model repository. Translational motion was enabled for each lumbar vertebrae with six controllable degrees of freedom. Motion segment stiffness was implemented at lumbar levels and mass properties were assigned throughout the model. Moreover, body coordinate frames of the spine were modified to allow straightforward variation of sagittal alignment and to simplify interpretation of results. Evaluation of model predictions for level L1–L2, L3–L4 and L4–L5 in various postures of forward flexion and moderate lifting (8 kg) revealed an agreement within 10% to experimental studies and model-based computational analyses. However, in an extended posture or during lifting of heavier loads (20 kg), computed joint reactions differed substantially from reported in vivo measures using instrumented implants. We conclude that agreement between the model and available experimental data was good in view of limitations of both the model and the validation datasets. The presented model is useful in that it permits computation of realistic lumbar spine joint reaction forces during flexion and moderate lifting tasks. The model and corresponding documentation are now available in the online OpenSim repository.     

The maize genetics and genomics database. The community resource for access to diverse maize data

The Maize Genetics and Genomics Database (MaizeGDB) serves the maize (Zea mays) research community by making a wealth of genetics and genomics data available through an intuitive Web-based interface. The goals of the MaizeGDB project are 3-fold: to provide a central repository for public maize information; to present the data through the MaizeGDB Web site in a way that recapitulates biological relationships; and to provide an array of computational tools that address biological questions in an easy-to-use manner at the site. In addition to these primary tasks, MaizeGDB team members also serve the community of maize geneticists by lending technical support for community activities, including the annual Maize Genetics Conference and various workshops, teaching researchers to use both the MaizeGDB Web site and Community Curation Tools, and engaging in collaboration with individual research groups to make their unique data types available through MaizeGDB.     

Plant-based microarray data at the European Bioinformatics Institute. Introducing AtMIAMExpress, a submission tool for Arabidopsis gene expression data to ArrayExpress

ArrayExpress is a public microarray repository founded on the Minimum Information About a Microarray Experiment (MIAME) principles that stores MIAME-compliant gene expression data. Plant-based data sets represent approximately one-quarter of the experiments in ArrayExpress. The majority are based on Arabidopsis (Arabidopsis thaliana); however, there are other data sets based on Triticum aestivum, Hordeum vulgare, and Populus subsp. AtMIAMExpress is an open-source Web-based software application for the submission of Arabidopsis-based microarray data to ArrayExpress. AtMIAMExpress exports data in MAGE-ML format for upload to any MAGE-ML-compliant application, such as J-Express and ArrayExpress. It was designed as a tool for users with minimal bioinformatics expertise, has comprehensive help and user support, and represents a simple solution to meeting the MIAME guidelines for the Arabidopsis community. Plant data are queryable both in ArrayExpress and in the Data Warehouse databases, which support queries based on gene-centric and sample-centric annotation. The AtMIAMExpress submission tool is available at http://www.ebi.ac.uk/at-miamexpress/. The software is open source and is available from http://sourceforge.net/projects/miamexpress/. For information, contact miamexpress@ebi.ac.uk.     

DNAssist: the integrated editing and analysis of molecular biology sequences in windows

MOTIVATION: The programs currently available for the analysis of nucleic acid and protein sequences suffer from a variety of problems: Web-based programs often require inconvenient reformatting of sequences when proceeding from one analysis to the next, and commercial-console-based programs are cost prohibitive. Here, we report the development of DNASSIST:, an inexpensive, multiple-document, interface program for the fully integrated editing and analysis of nucleic acid and protein sequences in the familiar environment of Microsoft Windows.     

ColBuilder: A server to build collagen fibril models

Type I collagen is the main structural component of many tissues in the human body. It provides excellent mechanical properties to connective tissue and acts as a protein interaction hub. There is thus a wide interest in understanding the properties and diverse functions of type I collagen at the molecular level. A precondition is an atomistic collagen I structure as it occurs in native tissue. To this end, we built full-atom models of cross-linked collagen fibrils by integrating the low-resolution structure of collagen fibril available from x-ray fiber diffraction with high-resolution structures of short collagen-like peptides from x-ray crystallography and mass spectrometry data. We created a Web resource of collagen models for 20 different species with a large variety of cross-link types and localization within the fibril to facilitate structure-based analyses and simulations of type I collagen in health and disease. To easily enable simulations, we provide parameters of the modeled cross-links for an Amber force field. The repository of collagen models is available at https://colbuilder.h-its.org.     

The CellML Model Repository

SUMMARY: The CellML Model Repository provides free access to over 330 biological models. The vast majority of these models are derived from published, peer-reviewed papers. Model curation is an important and ongoing process to ensure the CellML model is able to accurately reproduce the published results. As the CellML community grows, and more people add their models to the repository, model annotation will become increasingly important to facilitate data searches and information retrieval. AVAILABILITY: The CellML Model Repository is publicly accessible at http://www.cellml.org/models.     

Computing graphlet signatures of network nodes and motifs in Cytoscape with GraphletCounter

Biological network analysis can be enhanced by examining the connections between nodes and the rest of the network. For this purpose we have developed GraphletCounter, an open-source software tool for computing graphlet degree signatures that can operate on its own or as a plug-in to the network analysis environment Cytoscape. A unique characteristic of GraphletCounter is its ability to compute the graphlet signatures of network motifs, which can be specified by files generated by the motif-finding tool mfinder. GraphletCounter displays graphlet signatures for visual inspection within Cytoscape, and can output graphlet data for integration with larger workflows. AVAILABILITY AND IMPLEMENTATION: GraphletCounter is implemented in Java. It can be downloaded from the Cytoscape plugin repository, and is also available at http://sonmezsysbio.org/software/ graphletcounter.     

Gene-Expression Omnibus integration and clustering tools in SeqExpress

SeqExpress, a gene-expression analysis suite, has been extended to offer a number of cluster generation, refinement and visualization techniques. The cluster generation methods have been specialized to deal with aspects of the sparseness and extreme values that occur within microarray data. The results of such cluster analysis can then be refined using either: a functional enrichment based procedure, which examines each cluster to see if it possesses an unusually high or low concentration of ontology terms; or by using Expectation-Maximization to find a mixture of model based distributions within the datasets. Visualizations are provided both to explore and compare the results of the cluster generation algorithms. In addition, a tool has been developed which integrates SeqExpress with the Gene-Expression Omnibus repository. The tool provides seamless access to the large number of experimental results in the repository, so that they can be visualized and analysed locally using SeqExpress. AVAILABILITY: SeqExpress is available as a 6 MB download from http://www.seqexpress.com and runs under Windows. A server-based version is available and is required for the GEO integration. SeqExpress is not affiliated with any academic institution, funding body or commercial organization and is free to use by all.     

Dasty3, a WEB framework for DAS

MOTIVATION: Dasty3 is a highly interactive and extensible Web-based framework. It provides a rich Application Programming Interface upon which it is possible to develop specialized clients capable of retrieving information from DAS sources as well as from data providers not using the DAS protocol. Dasty3 provides significant improvements on previous Web-based frameworks and is implemented using the 1.6 DAS specification. AVAILABILITY: Dasty3 is an open-source tool freely available at http://www.ebi.ac.uk/dasty/ under the terms of the GNU General public license. Source and documentation can be found at http://code.google.com/p/dasty/. CONTACT: hhe@ebi.ac.uk.     

A systematic comparative and structural analysis of protein phosphorylation sites based on the mtcPTM database

mtcPTM is an online repository of human and mouse phosphosites in which data are hierarchically organized to preserve biologically relevant experimental information, thus allowing straightforward comparisons of phosphorylation patterns found under different conditions. The database also contains the largest available collection of atomic models of phosphorylatable proteins. Detailed analysis of this structural dataset reveals that phosphorylation sites are found in a heterogeneous range of structural and sequence contexts. mtcPTM is available on the web .     

affylmGUI: a graphical user interface for linear modeling of single channel microarray data

SUMMARY: affylmGUI is a graphical user interface (GUI) to an integrated workflow for Affymetrix microarray data. The user is able to proceed from raw data (CEL files) to QC and pre-processing, and eventually to analysis of differential expression using linear models with empirical Bayes smoothing. Output of the analysis (tables and figures) can be exported to an HTML report. The GUI provides user-friendly access to state-of-the-art methods embodied in the Bioconductor software repository. AVAILABILITY: affylmGUI is an R package freely available from http://www.bioconductor.org. It requires R version 1.9.0 or later and tcl/tk 8.3 or later and has been successfully tested on Windows 2000, Windows XP, Linux (RedHat and Fedora distributions) and Mac OS/X with X11. Further documentation is available at http://bioinf.wehi.edu.au/affylmGUI CONTACT: keith@wehi.edu.au.     

Mouse tumor biology database (MTB): enhancements and current status

The Mouse Tumor Biology Database (MTB) is a Web-based resource that provides access to information on tumor frequency and latency, genetics and pathology in genetically defined mice (transgenics, targeted mutations and inbred strains). MTB is designed to serve as an information resource for cancer genetics researchers who use the laboratory mouse as a model system for understanding human disease processes. Data in MTB are obtained from the primary scientific literature and direct submissions by the research community. MTB is accessible from the Mouse Genome Informatics Web site (http://www. informatics.jax.org). User support is available for MTB via Email at mgi-help@informatics.jax.org     

An Open Source 3-D Printed Modular Micro-Drive System for Acute Neurophysiology

Current, commercial, electrode micro-drives that allow independent positioning of multiple electrodes are expensive. Custom designed solutions developed by individual laboratories require fabrication by experienced machinists working in well equipped machine shops and are therefore difficult to disseminate into widespread use. Here, we present an easy to assemble modular micro-drive system for acute primate neurophysiology (PriED) that utilizes rapid prototyping (3-d printing) and readily available off the shelf-parts. The use of 3-d printed parts drastically reduces the cost of the device, making it available to labs without the resources of sophisticated machine shops. The direct transfer of designs from electronic files to physical parts also gives researchers opportunities to easily modify and implement custom solutions to specific recording needs. We also demonstrate a novel model of data sharing for the scientific community: a publicly available repository of drive designs. Researchers can download the drive part designs from the repository, print, assemble and then use the drives. Importantly, users can upload their modified designs with annotations making them easily available for others to use.     

PSAMM: A Portable System for the Analysis of Metabolic Models

The genome-scale models of metabolic networks have been broadly applied in phenotype prediction, evolutionary reconstruction, community functional analysis, and metabolic engineering. Despite the development of tools that support individual steps along the modeling procedure, it is still difficult to associate mathematical simulation results with the annotation and biological interpretation of metabolic models. In order to solve this problem, here we developed a Portable System for the Analysis of Metabolic Models (PSAMM), a new open-source software package that supports the integration of heterogeneous metadata in model annotations and provides a user-friendly interface for the analysis of metabolic models. PSAMM is independent of paid software environments like MATLAB, and all its dependencies are freely available for academic users. Compared to existing tools, PSAMM significantly reduced the running time of constraint-based analysis and enabled flexible settings of simulation parameters using simple one-line commands. The integration of heterogeneous, model-specific annotation information in PSAMM is achieved with a novel format of YAML-based model representation, which has several advantages, such as providing a modular organization of model components and simulation settings, enabling model version tracking, and permitting the integration of multiple simulation problems. PSAMM also includes a number of quality checking procedures to examine stoichiometric balance and to identify blocked reactions. Applying PSAMM to 57 models collected from current literature, we demonstrated how the software can be used for managing and simulating metabolic models. We identified a number of common inconsistencies in existing models and constructed an updated model repository to document the resolution of these inconsistencies.