Systems Biology Markup Language Files Research Articles

The Systems Biology Markup Language (SBML) Level 3 Package: Layout, Version 1 Core

SummaryMany software tools provide facilities for depicting reaction network diagrams in a visual form. Two aspects of such a visual diagram can be distinguished: the layout (i.e.: the positioning and connections) of the elements in the diagram, and the graphical form of the elements (for example, the glyphs used for symbols, the properties of the lines connecting them, and so on). For software tools that also read and write models in SBML (Systems Biology Markup Language) format, a common need is to store the network diagram together with the SBML representation of the model. This in turn raises the question of how to encode the layout and the rendering of these diagrams. The SBML Level 3 Version 1 Core specification does not provide a mechanism for explicitly encoding diagrams, but it does provide a mechanism for SBML packages to extend the Core specification and add additional syntactical constructs. The Layout package for SBML Level 3 adds the necessary features to SBML so that diagram layouts can be encoded in SBML files, and a companion package called SBML Rendering specifies how the graphical rendering of elements can be encoded.The SBML Layout package is based on the principle that reaction network diagrams should be described as representations of entities such as species and reactions (with direct links to the underlying SBML elements), and not as arbitrary drawings or graphs; for this reason, existing languages for the description of vector drawings (such as SVG) or general graphs (such as GraphML) cannot be used.

Version 6 of the consensus yeast metabolic network refines biochemical coverage and improves model performance.

Updates to maintain a state-of-the art reconstruction of the yeast metabolic network are essential to reflect our understanding of yeast metabolism and functional organization, to eliminate any inaccuracies identified in earlier iterations, to improve predictive accuracy and to continue to expand into novel subsystems to extend the comprehensiveness of the model. Here, we present version 6 of the consensus yeast metabolic network (Yeast 6) as an update to the community effort to computationally reconstruct the genome-scale metabolic network of Saccharomyces cerevisiae S288c. Yeast 6 comprises 1458 metabolites participating in 1888 reactions, which are annotated with 900 yeast genes encoding the catalyzing enzymes. Compared with Yeast 5, Yeast 6 demonstrates improved sensitivity, specificity and positive and negative predictive values for predicting gene essentiality in glucose-limited aerobic conditions when analyzed with flux balance analysis. Additionally, Yeast 6 improves the accuracy of predicting the likelihood that a mutation will cause auxotrophy. The network reconstruction is available as a Systems Biology Markup Language (SBML) file enriched with Minimium Information Requested in the Annotation of Biochemical Models (MIRIAM)-compliant annotations. Small- and macromolecules in the network are referenced to authoritative databases such as Uniprot or ChEBI. Molecules and reactions are also annotated with appropriate publications that contain supporting evidence. Yeast 6 is freely available at http://yeast.sf.net/ as three separate SBML files: a model using the SBML level 3 Flux Balance Constraint package, a model compatible with the MATLAB® COBRA Toolbox for backward compatibility and a reconstruction containing only reactions for which there is experimental evidence (without the non-biological reactions necessary for simulating growth).Database URL: http://yeast.sf.net/

Glycosylation Network Analysis Toolbox: a MATLAB-based environment for systems glycobiology

Systems glycobiology studies the interaction of various pathways that regulate glycan biosynthesis and function. Software tools for the construction and analysis of such pathways are not yet available. We present GNAT, a platform-independent, user-extensible MATLAB-based toolbox that provides an integrated computational environment to construct, manipulate and simulate glycans and their networks. It enables integration of XML-based glycan structure data into SBML (Systems Biology Markup Language) files that describe glycosylation reaction networks. Curation and manipulation of networks is facilitated using class definitions and glycomics database query tools. High quality visualization of networks and their steady-state and dynamic simulation are also supported. The software package including source code, help documentation and demonstrations are available at http://sourceforge.net/projects/gnatmatlab/files/.

JSBML: a flexible and entirely Java-based library for working with SBML

AbstractThe XML-based Systems Biology Markup Language (SBML) is the de facto standard file format for the storage and exchange of biochemical network models, and is supported by more than 180 software packages to date. Much of this success is due to its clearly defined specifications and the availability of libSBML, a portable, robust, and easy-to-use library.LibSBML provides many methods for manipulating and validating SBML files through its Application Programming Interface (API). Originally written in C and C++, libSBML also provides automatically-generated language bindings for Java, MATLAB, Perl, and many more. However, the platform independence of Java is compromised in libSBML due to the fact that the language binding is a wrapper around the C/C++ core. The real-world experiences of many software developers has been that the deployment of portable libSBML-based Java applications is difficult. Further, the libSBML API and type hierarchy are not sufficiently intuitive from a Java programmer's perspective just because they were not designed directly for Java. For these reasons, several groups in the SBML community have mounted an open-source effort to develop a pure Java library for SBML. Here we present the JSBML project, whose products are freely available at the web site http://sourceforge.net/projects/jsbml.

SBML and MathML support for the stochastic reaction-diffusion simulator STEPS

STEPS is a stochastic signaling pathway simulator based on the “spatial Gillespie” method for reaction-diffusion simulation, within a Python interface [1]. STEPS supports tetrahedral meshes, which allow for complex boundary representation absent from simulators based on cubic voxels. A powerful addition to STEPS, the membrane potential calculation, is under development. The potential of nodes throughout the tetrahedral mesh are simulated, which allows for the inclusion of voltage-gated membrane channels with molecular channel currents within the simulation. STEPS supports spatial and non-spatial simulations, and future versions will even allow for a combination of spatial and well-mixed compartments in one simulation. The Systems Biology Markup Language (SBML) is a widely used format for representing models of networks of biochemical interactions. The neuronal signaling pathways that STEPS is designed to simulate in a well-mixed context fall under this umbrella. While it was found that the Python interfaces to STEPS and libSBML makes it an ease to support most components of SBML, in some models there may be hurdles that cannot be overcome in a STEPS context and also any other stochastic simulation context. Stochastic simulation approaches, including the SSA that STEPS is based on, assumes that each reaction is the most fundamental with no intermediate, non-simulated steps. Therefore the expected form of the mathematics for the reaction rate is easily definable, but may differ from the explicit mathematics specified in some SBML files. If STEPS were to ignore alternate reaction kinetic law mathematics then any model that included such would be represented incorrectly. An example is a catalyst reaction that may often be described as a single reaction whose kinetic mathematics is influenced by the catalyst, which should typically be broken down into three or more separate reactions in the stochastic description. STEPS performs a comparison of the reaction kinetic law mathematics to the form that is expected, which means that a model will never be simulated incorrectly. This is achieved by converting the MathML components in SBML, including reaction kinetic law mathematics, to Python objects with no limit on depth. MathML support in the Python interface then makes it easy to support other features of SBML that are based on MathML, which are numerous. This is because the MathML Python objects are available during simulation and may reference any variable in the model including those whose value is not constant during simulation. This extends SBML support in STEPS to many components that other stochastic simulators cannot support because they ignore MathML, including important features such as Initial Assignments, Assignment Rules, Rate Rules and Events.

JSBML

AbstractThe XML-based Systems Biology Markup Language (SBML) is the de facto standard file format for the storage and exchange of biochemical network models, and is supported by more than 180 software packages to date. Much of this success is due to SBML's clearly defined specifications and the availability of libSBML, a portable, robust and easy-to-use library.LibSBML provides many methods for manipulating and validating SBML files through its Application Programming Interface (API). Originally written in C and C++, libSBML also provides automatically-generated language bindings for Java, MATLAB, Perl, Python, and many more. However, the platform independence of Java is compromised in libSBML due to the fact that the language binding is a wrapper around the C/C++ core. The real-world experiences of many software developers has been that the deployment of portable libSBML-based Java applications is difficult. Further, the libSBML API and type hierarchy are not sufficiently intuitive from a Java programmer's perspective simply because they were not designed directly for Java.For these reasons, several groups in the SBML community have mounted an open-source effort to develop a pure Java library for SBML. Here we present the JSBML project, whose products are freely available at the website "http://jsbml.sourceforge.net/":http://jsbml.sourceforge.net/. The JSBML project's aim is to provide an SBML parser and programming library that maps all SBML elements to a flexible and extended type hierarchy. Where possible, JSBML strives to attain 100% API compatibility with the libSBML Java API, to facilitate a switch from one library to the other for those who desire it.Currently, JSBML supports all constructs for SBML up to the latest Level 3 Version 1 release candidate specification, including an API to add SBML extensions. There are no plans to re-implement some of the more complex functions of libSBML, since separate community efforts are expected to make them available to JSBML via web services. These more complex functions include model consistency checking, SBML validation, and the conversion between different SBML Levels and Versions.In summary, JSBML is a young, ongoing software project that provides comprehensive and entirely Java-based data structures to read, write, and manipulate SBML files. Its layered architecture allows for the creation of Java web start applications and CellDesigner plug-ins based on stand-alone programs with very little effort. One program, SBMLsqueezer 1.3, has already been re-implemented and released using JSBML, and many others are planned.

JSBML

The XML-based Systems Biology Markup Language (SBML) is the de facto standard file format for the storage and exchange of biochemical network models, and is supported by more than 180 software packages to date. Much of this success is due to SBML's clearly defined specifications and the availability of libSBML, a portable, robust and easy-to-use library.LibSBML provides many methods for manipulating and validating SBML files through its Application Programming Interface (API). Originally written in C and C++, libSBML also provides automatically-generated language bindings for Java, MATLAB, Perl, Python, and many more. However, the platform independence of Java is compromised in libSBML due to the fact that the language binding is a wrapper around the C/C++ core. The real-world experiences of many software developers has been that the deployment of portable libSBML-based Java applications is difficult. Further, the libSBML API and type hierarchy are not sufficiently intuitive from a Java programmer's perspective simply because they were not designed directly for Java.For these reasons, several groups in the SBML community have mounted an open-source effort to develop a pure Java library for SBML. Here we present the JSBML project, whose products are freely available at the website "http://jsbml.sourceforge.net/":http://jsbml.sourceforge.net/. The JSBML project's aim is to provide an SBML parser and programming library that maps all SBML elements to a flexible and extended type hierarchy. Where possible, JSBML strives to attain 100% API compatibility with the libSBML Java API, to facilitate a switch from one library to the other for those who desire it.Currently, JSBML supports all constructs for SBML up to the latest Level 3 Version 1 release candidate specification, including an API to add SBML extensions. There are no plans to re-implement some of the more complex functions of libSBML, since separate community efforts are expected to make them available to JSBML via web services. These more complex functions include model consistency checking, SBML validation, and the conversion between different SBML Levels and Versions.In summary, JSBML is a young, ongoing software project that provides comprehensive and entirely Java-based data structures to read, write, and manipulate SBML files. Its layered architecture allows for the creation of Java web start applications and CellDesigner plug-ins based on stand-alone programs with very little effort. One program, SBMLsqueezer 1.3, has already been re-implemented and released using JSBML, and many others are planned.

LibAnnotationSBML: a library for exploiting SBML annotations

Summary: The Systems Biology Markup Language (SBML) is an established community XML format for the markup of biochemical models. With the introduction of SBML level 2 version 3, specific model entities, such as species or reactions, can now be annotated using ontological terms. These annotations, which are encoded using the resource description framework (RDF), provide the facility to specify definite terms to individual components, allowing software to unambiguously identify such components and thus link the models to existing data resources.libSBML is an application programming interface library for the manipulation of SBML files. While libSBML provides the facilities for reading and writing such annotations from and to models, it is beyond the scope of libSBML to provide interpretation of these terms. The libAnnotationSBML library introduced here acts as a layer on top of libSBML linking SBML annotations to the web services that describe these ontological terms. Two applications that use this library are described: SbmlSynonymExtractor finds name synonyms of SBML model entities and SbmlReactionBalancer checks SBML files to determine whether specifed reactions are elementally balanced.Availability: http://mcisb.sourceforge.net/Contact: neil.swainston@manchester.ac.uk

Curation and annotation for BioModels Database, a resource of published quantitative kinetic models

AbstractBioModels Database ("http://www.ebi.ac.uk/biomodels/":http://www.ebi.ac.uk/biomodels/) is a free resource for storing, viewing and retrieving published, peer-reviewed, quantitative models of biochemical and cellular systems. As a storage format, BioModels Database uses the Systems Biology Markup Language (SBML), but also allows submission and export of models in various other commonly used formats.To offer scientists reliable information, models are curated to comply with the MIRIAM (Minimal Information Requested In the Annotation of biochemical Models) standard. This curation process involves verification of the model structure, the parameter and variable values and its mathematical relations. Furthermore reproduction of results in the reference publication is checked.The different elements of the models are extensively annotated with references to controlled vocabularies and links to other databases, to allow for identification and search. Those references and links are provided in the exported SBML files as a URN (Uniform Resource Name), identifying the data-type and the data-set, and a qualifier, indicating the relation between the element and the referenced data-set. The URNs follow the MIRIAM scheme and are resolved, for instance to URLs, using the Web Services of MIRIAM Resources ("http://www.ebi.ac.uk/miriam/":http://www.ebi.ac.uk/miriam/).

Curation and annotation for BioModels Database, a resource of published quantitative kinetic models

BioModels Database ("http://www.ebi.ac.uk/biomodels/":http://www.ebi.ac.uk/biomodels/) is a free resource for storing, viewing and retrieving published, peer-reviewed, quantitative models of biochemical and cellular systems. As a storage format, BioModels Database uses the Systems Biology Markup Language (SBML), but also allows submission and export of models in various other commonly used formats.To offer scientists reliable information, models are curated to comply with the MIRIAM (Minimal Information Requested In the Annotation of biochemical Models) standard. This curation process involves verification of the model structure, the parameter and variable values and its mathematical relations. Furthermore reproduction of results in the reference publication is checked.The different elements of the models are extensively annotated with references to controlled vocabularies and links to other databases, to allow for identification and search. Those references and links are provided in the exported SBML files as a URN (Uniform Resource Name), identifying the data-type and the data-set, and a qualifier, indicating the relation between the element and the referenced data-set. The URNs follow the MIRIAM scheme and are resolved, for instance to URLs, using the Web Services of MIRIAM Resources ("http://www.ebi.ac.uk/miriam/":http://www.ebi.ac.uk/miriam/).

SBML2LaTEX: Conversion of SBML files into human-readable reports

Summary: The XML-based Systems Biology Markup Language (SBML) has emerged as a standard for storage, communication and interchange of models in systems biology. As a machine-readable format XML is difficult for humans to read and understand. Many tools are available that visualize the reaction pathways stored in SBML files, but many components, e.g. unit declarations, complex kinetic equations or links to MIRIAM resources, are often not made visible in these diagrams. For a broader understanding of the models, support in scientific writing and error detection, a human-readable report of the complete model is needed. We present SBML2LaTEX, a Java-based stand-alone program to fill this gap. A convenient web service allows users to directly convert SBML to various formats, including DVI, LaTEX and PDF, and provides many settings for customization.Availability: Source code, documentation and a web service are freely available at http://www.ra.cs.uni-tuebingen.de/software/SBML2LaTeX.Contact:andreas.draeger@uni-tuebingen.deSupplementary information:Supplementary data are available at Bioinformatics online.

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. 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.

SBMLeditor: effective creation of models in the Systems Biology Markup language (SBML).

BackgroundThe need to build a tool to facilitate the quick creation and editing of models encoded in the Systems Biology Markup language (SBML) has been growing with the number of users and the increased complexity of the language. SBMLeditor tries to answer this need by providing a very simple, low level editor of SBML files. Users can create and remove all the necessary bits and pieces of SBML in a controlled way, that maintains the validity of the final SBML file.ResultsSBMLeditor is written in JAVA using JCompneur, a library providing interfaces to easily display an XML document as a tree. This decreases dramatically the development time for a new XML editor. The possibility to include custom dialogs for different tags allows a lot of freedom for the editing and validation of the document. In addition to Xerces, SBMLeditor uses libSBML to check the validity and consistency of SBML files. A graphical equation editor allows an easy manipulation of MathML. SBMLeditor can be used as a module of the Systems Biology Workbench.ConclusionSBMLeditor contains many improvements compared to a generic XML editor, and allow users to create an SBML model quickly and without syntactic errors.