SBMLToolbox: an SBML toolbox for MATLAB users

SUMMARY: We present SBMLToolbox, a toolbox that facilitates importing and exporting models represented in the Systems Biology Markup Language (SBML) in and out of the MATLAB environment and provides functionality that enables an experienced user of either SBML or MATLAB to combine the computing power of MATLAB with the portability and exchangeability of an SBML model. SBMLToolbox supports all levels and versions of SBML. AVAILABILITY: SBMLToolbox is freely available from http://sbml.org/software/sbmltoolbox     

LibSBML: an API library for SBML

Summary: LibSBML is an application programming interface libraryfor reading, writing, manipulating and validating content expressedin the Systems Biology Markup Language (SBML) format. It iswritten in ISO C and C++, provides language bindings for CommonLisp, Java, Python, Perl, MATLAB and Octave, and includes manyfeatures that facilitate adoption and use of both SBML and thelibrary. Developers can embed libSBML in their applications,saving themselves the work of implementing their own SBML parsing,manipulation and validation software. Availability: LibSBML 3 was released in August 2007. Sourcecode, binaries and documentation are freely available underLGPL open-source terms from http://sbml.org/software/libsbml. Contact: sbml-team{at}caltech.edu Associate Editor: Olga Troyanskaya The first two authors should be regarded as First Author.     

Systems Biology Toolbox for MATLAB: a computational platform for research in systems biology

We present a Systems Biology Toolbox for the widely used general purpose mathematical software MATLAB. The toolbox offers systems biologists an open and extensible environment, in which to explore ideas, prototype and share new algorithms, and build applications for the analysis and simulation of biological and biochemical systems. Additionally it is well suited for educational purposes. The toolbox supports the Systems Biology Markup Language (SBML) by providing an interface for import and export of SBML models. In this way the toolbox connects nicely to other SBML-enabled modelling packages. Models are represented in an internal model format and can be described either by entering ordinary differential equations or, more intuitively, by entering biochemical reaction equations. The toolbox contains a large number of analysis methods, such as deterministic and stochastic simulation, parameter estimation, network identification, parameter sensitivity analysis and bifurcation analysis.     

Cyto-Sim: a formal language model and stochastic simulator of membrane-enclosed biochemical processes

MOTIVATION: Compartments and membranes are the basis of cell topology and more than 30% of the human genome codes for membrane proteins. While it is possible to represent compartments and membrane proteins in a nominal way with many mathematical formalisms used in systems biology, few, if any, explicitly model the topology of the membranes themselves. Discrete stochastic simulation potentially offers the most accurate representation of cell dynamics. Since the details of every molecular interaction in a pathway are often not known, the relationship between chemical species in not necessarily best described at the lowest level, i.e. by mass action. Simulation is a form of computer-aided analysis, relying on human interpretation to derive meaning. To improve efficiency and gain meaning in an automatic way, it is necessary to have a formalism based on a model which has decidable properties. RESULTS: We present Cyto-Sim, a stochastic simulator of membrane-enclosed hierarchies of biochemical processes, where the membranes comprise an inner, outer and integral layer. The underlying model is based on formal language theory and has been shown to have decidable properties (Cavaliere and Sedwards, 2006), allowing formal analysis in addition to simulation. The simulator provides variable levels of abstraction via arbitrary chemical kinetics which link to ordinary differential equations. In addition to its compact native syntax, Cyto-Sim currently supports models described as Petri nets, can import all versions of SBML and can export SBML and MATLAB m-files. AVAILABILITY: Cyto-Sim is available free, either as an applet or a stand-alone Java program via the web page (http://www.cosbi.eu/Rpty_Soft_CytoSim.php). Other versions can be made available upon request.     

CellML2SBML: conversion of CellML into SBML

CellML and SBML are XML-based languages for storage and exchange of molecular biological and physiological reaction models. They use very similar subsets of MathML to specify the mathematical aspects of the models. CellML2SBML is implemented as a suite of XSLT stylesheets that, when applied consecutively, convert models expressed in CellML into SBML without significant loss of information. The converter is based on the most recent stable versions of the languages (CellML version 1.1; SBML Level 2 Version 1), and the XSLT used in the stylesheets adheres to the XSLT version 1.0 specification. Of all 306 models in the CellML repository in April 2005, CellML2SBML converted 91% automatically into SBML. Minor manual changes to the unit definitions in the originals raised the percentage of successful conversions to 96%. Availability: http://sbml.org/software/cellml2sbml/. Supplementary information: Instructions for use and further documentation available on http://sbml.org/software/cellml2sbml/     

Tools for the SBML Community

MOTIVATION: SBML is quickly becoming the standard format to exchange biochemical models. The tools presented in this paper are loosely-coupled, and are intended to be incorporated into SBML aware applications. The rationale for this is to reduce the amount of repeated work carried out within the community and to create tools that offer a greater number of features to the end-user. AVAILABILITY: All tools described are available from http://www.basis.ncl.ac.uk/software and are licensed under GNU General Public License.     

MIRACH: efficient model checker for quantitative biological pathway models

Model checking is playing an increasingly important role in systems biology as larger and more complex biological pathways are being modeled. In this article we report the release of an efficient model checker MIRACH 1.0, which supports any model written in popular formats such as CSML and SBML. MIRACH is integrated with a Petri-net-based simulation engine, enabling efficient online (on-the-fly) checking. In our experiment, by using Levchenko et al. model, we reveal that timesaving gains by using MIRACH easily surpass 400% compared with its offline-based counterpart. AVAILABILITY AND IMPLEMENTATION: MIRACH 1.0 was developed using Java and thus executable on any platform installed with JDK 6.0 (not JRE 6.0) or later. MIRACH 1.0, along with its source codes, documentation and examples are available at http://sourceforge.net/projects/mirach/ under the LGPLv3 license.     

SBML-PET: a Systems Biology Markup Language-based parameter estimation tool

The estimation of model parameters from experimental data remains a bottleneck for a major breakthrough in systems biology. We present a Systems Biology Markup Language (SBML) based Parameter Estimation Tool (SBML-PET). The tool is designed to enable parameter estimation for biological models including signaling pathways, gene regulation networks and metabolic pathways. SBML-PET supports import and export of the models in the SBML format. It can estimate the parameters by fitting a variety of experimental data from different experimental conditions. SBML-PET has a unique feature of supporting event definition in the SMBL model. SBML models can also be simulated in SBML-PET. Stochastic Ranking Evolution Strategy (SRES) is incorporated in SBML-PET for parameter estimation jobs. A classic ODE Solver called ODEPACK is used to solve the Ordinary Differential Equation (ODE) system. AVAILABILITY: http://sysbio.molgen.mpg.de/SBML-PET/. The website also contains detailed documentation for SBML-PET.     

SBML export interface for the systems biology toolbox for MATLAB

In this application note, we present an Systems biology markup language (SBML) export interface for the Systems Biology Toolbox for MATLAB. This interface allows modelers to automatically convert models, represented in the toolbox's own format (SBmodels) to SBML files. Since SBmodels do not explicitly contain all the information that is required to generate SBML, the necessary information is gathered by parsing SBmodels. The export can be done in two different ways. First, it is possible to call the export from the command line, thereby directly converting a model to an SBML file. The second option is to inspect and edit the conversion results with the help of a graphical user interface and to subsequently export the model to SBML. Availability: The SBML export interface has been integrated into the Systems Biology Toolbox for MATLAB, which is open source and freely available from http://www.sbtoolbox.org. The website also contains a tutorial, extensive documentation and examples.     

Automated manipulation of systems biology models using libSBML within Taverna workflows

Many data manipulation processes involve the use of programming libraries. These processes may beneficially be automated due to their repeated use. A convenient type of automation is in the form of workflows that also allow such processes to be shared amongst the community. The Taverna workflow system has been extended to enable it to use and invoke Java classes and methods as tasks within Taverna workflows. These classes and methods are selected for use during workflow construction by a Java Doclet application called the API Consumer. This selection is stored as an XML file which enables Taverna to present the subset of the API for use in the composition of workflows. The ability of Taverna to invoke Java classes and methods is demonstrated by a workflow in which we use libSBML to map gene expression data onto a metabolic pathway represented as a SBML model. AVAILABILITY: Taverna and the API Consumer application can be freely downloaded from http://taverna.sourceforge.net     

Java Treeview--extensible visualization of microarray data

Open source software encourages innovation by allowing users to extend the functionality of existing applications. Treeview is a popular application for the visualization of microarray data, but is closed-source and platform-specific, which limits both its current utility and suitability as a platform for further development. Java Treeview is an open-source, cross-platform rewrite that handles very large datasets well, and supports extensions to the file format that allow the results of additional analysis to be visualized and compared. The combination of a general file format and open source makes Java Treeview an attractive choice for solving a class of visualization problems. An applet version is also available that can be used on any website with no special server-side setup.     

TO-GO: a Java-based Gene Ontology navigation environment

SUMMARY: TO-GO is a Gene Ontology (GO) navigation tool, which is implemented as a Java application. After the initial data downloading, the GO term tree can be interactively navigated without further network transfer. Local annotation can be incorporated. It supports querying by GO terms or associated gene product information, displaying the result as a table or a sub-tree. The result from the search for a set of external database accessions includes the number of gene products associated with each node, inclusive of sub-nodes. Search results can be further processed by set operations and these set operations can be quite useful for expression profile data analysis. A copy/paste function is also implemented in order to facilitate data exchange between applications. AVAILABILITY: TO-GO is freely available at http://www.ngic.re.kr/togo/index.html CONTACT: ungsik@kribb.re.kr     

UniProtJAPI: a remote API for accessing UniProt data

Programmatic access to the UniProt Knowledgebase (UniProtKB) is essential for many bioinformatics applications dealing with protein data. We have created a Java library named UniProtJAPI, which facilitates the integration of UniProt data into Java-based software applications. The library supports queries and similarity searches that return UniProtKB entries in the form of Java objects. These objects contain functional annotations or sequence information associated with a UniProt entry. Here, we briefly describe the UniProtJAPI and demonstrate its usage.     

MetaQuant: a tool for the automatic quantification of GC/MS-based metabolome data

MetaQuant is a Java-based program for the automatic and accurate quantification of GC/MS-based metabolome data. In contrast to other programs MetaQuant is able to quantify hundreds of substances simultaneously with minimal manual intervention. The integration of a self-acting calibration function allows the parallel and fast calibration for several metabolites simultaneously. Finally, MetaQuant is able to import GC/MS data in the common NetCDF format and to export the results of the quantification into Systems Biology Markup Language (SBML), Comma Separated Values (CSV) or Microsoft Excel (XLS) format. AVAILABILITY: MetaQuant is written in Java and is available under an open source license. Precompiled packages for the installation on Windows or Linux operating systems are freely available for download. The source code as well as the installation packages are available at http://bioinformatics.org/metaquant     

JDotter: a Java interface to multiple dotplots generated by dotter

Java-Dotter (JDotter) is a platform-independent Java interactive interface for the Linux version of Dotter, a widely used program for generating dotplots of large DNA or protein sequences. JDotter runs as a client-server application and can send new sequences to the Dotter program for alignment as well as rapidly access a repository of preprocessed dotplots. JDotter also interfaces with a sequence database or file system to display supplementary feature data. Thus, JDotter greatly simplifies access to dotplot data in laboratories that deal with large numbers of genomes and have a multi-platform organization. AVAILABILITY: Currently, JDotter is used via Java Web Start by the Poxvirus Bioinformatics Resource for examining dotplots of complete poxvirus genomes; http://athena.bioc.uvic.ca/pbr/jdotter/. The software is available for download from the same location. SUPPLEMENTARY INFORMATION: Installation instructions, the User's Manual, screenshots and examples are available at the JDotter home page http://athena.bioc.uvic.ca/pbr/jdotter/. The software and source code is free for non-commercial applications.     

Construction,visualization, and analysis of biological network models in Dynetica

Mathematical modeling has become an increasingly important aspect of biological research. Computer simulations help to improve our understanding of complex systems by testing the validity of proposed mechanisms and generating experimentally testable hypotheses. However, significant overhead is generated by the creation, debugging, and perturbation of these computational models and their parameters, especially for researchers who are unfamiliar with programming or numerical methods. Dynetica 2.0 is a user-friendly dynamic network simulator designed to expedite this process. Models are created and visualized in an easy-to-use graphical interface, which displays all of the species and reactions involved in a graph layout. System inputs and outputs, indicators, and intermediate expressions may be incorporated into the model via the versatile “expression variable” entity. Models can also be modular, allowing for the quick construction of complex systems from simpler components. Dynetica 2.0 supports a number of deterministic and stochastic algorithms for performing time-course simulations. Additionally, Dynetica 2.0 provides built-in tools for performing sensitivity or dose response analysis for a number of different metrics. Its parameter searching tools can optimize specific objectives of the time course or dose response of the system. Systems can be translated from Dynetica 2.0 into MATLAB code or the Systems Biology Markup Language (SBML) format for further analysis or publication. Finally, since it is written in Java, Dynetica 2.0 is platform independent, allowing for easy sharing and collaboration between researchers.