SBMLeditor: effective creation of models in the Systems Biology Markup Language (SBML)
© Rodriguez et al; licensee BioMed Central Ltd. 2007
Received: 30 November 2006
Accepted: 06 March 2007
Published: 06 March 2007
The 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.
SBMLeditor 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.
SBMLeditor contains many improvements compared to a generic XML editor, and allow users to create an SBML model quickly and without syntactic errors.
Systems Biology Markup Language – SBML
In Systems Biology, complementary computational tools are often used to model and analyse different characteristics of a particular system. Most tools have their own specific format for entering and storing models, and switching tools not long ago most often required re-writing the model from scratch. Moreover, when a tool was no longer supported, models could be lost forever.
The Systems Biology Markup Language (SBML) is a free, open, XML-based format designed to promote interoperability between different tools . Model descriptions produced by one tool can be read and processed by other programs. It also offers a standard representation for model storage, transmission, and re-use. SBML can be used for describing models of (but not restricted to) signalling pathways, metabolic networks, gene regulation networks, etc. SBML is specified as a set of class descriptions, and can be implemented in very different ways. Currently it is mainly instantiated as an XML language .
Although SBML is text-based, and can be edited in a simple text editor, it is intended to be written and read by machines, not by human beings. As such, it requires specific user-interfaces to translate modeller's intentions into its computer representation.
The main target users of this SBML editor are scientists using different software to develop and simulate their models and who spend significant time editing by hand their models, either to enter small modifications or even to write complete models. The need to build a specific tool to facilitate the quick creation and editing of correct SBML files has been growing both with the number of SBML users, and the increased complexity of the SBML Level 2 format  (a problem that will increase with the future Level 3). SBMLeditor tries to answer these needs 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 and consistency of the final SBML file. In addition, SBMLeditor provides a tool covering 100% of the SBML specifications, either Level 1 or Level 2, without being hindered by software-specific constraints. Finally, this editor allows investigators to implement and test quickly new SBML proposals, such as the controlled annotations part of SBML Level 2 Version 2 .
SBMLeditor is written with the Java GUI toolkit Swing. Xerces  is used to parse the SBML files through the Document Object Model (DOM) . JCompneur, a library written by Marco Donizelli, is then used to display and edit this DOM tree as a Java JTree. JCompneur has already been used in several projects to edit file according to differents XML schemas, and is quite easy to use and customize for any need. It offers a serie of Java interfaces that one can use to create, edit and filter XML nodes. The creation and editing of XML nodes is made following the Template pattern  with preAction(), action() and postAction() methods. During the action, a customized JPanel is displayed to the user, where he can enter the required information. Wherever it is possible, the choice offered to the user is restricted with lists of choices, reducing the selection errors. However, many constraints on a SBML file are only defined in the SBML specification, and not in the XML schema. Therefore, some errors can go through despite the built-in constraints. We use libSBML , the library written by the SBML Team, to check the consistency of the resulting SBML file. This library is written in C, with a Java interface using the Simplified Wrapper and Interface Generator (SWIG) .
LibSBML is also used to manipulate the Mathematical Markup Language (MathML)  content, included in some of the SBML elements. A function is used to transform the MathML into an infix formula and conversely. All the references to SBML elements in MathML expressions are made to the attribute "id" of the elements. The value of these ids is restricted by a pattern (see section 3.1.7 of the SBML specifications) and some software might create unique ids without meaning. Each relevant SBML element also possess an attribute "name", supposed to be human readable. Each id is substitued by the corresponding name if it exists. The resulting formula is then displayed in a customize Jex  panel, where some coloring is added to distinguish between the different types of SBML element.
Library for XML editing
In order to facilitate the development of several projects involving the editing of XML files, we developed a generic library, JCompneur. SBMLeditor is built on top of the library, with only a limited number of additions. A custom dialog is created to allow one to create or edit SBML elements. The NodeTreeCellRenderer class has been extended to customize the display of the tree. For instance, SBMLeditor does not display the complete DOM tree of the elements notes, annotation or math, containing XML elements that do not belong to SBML namespace. Instead, the editor displays the sub-tree inside a TextArea. In turn, this allows users to customise the rendering of some subtree in the editor. For instance, the content of the element notes is XHTML. In the tree, the XHTML is interpreted and the notes are displayed as they would be in a web browser, the XHTML tags being only visible in the editing window. The methods create and process node are based on the Template Pattern. For example, the create method is splitted into the following steps:
Set some properties (size, location, etc.) of the dialog.
Make the dialog visible.
Wait until the dialog is no longer visible.
If the OK button was pressed, invoke postCreate otherwise invoke resetCreate
Return the newly created XML DOM element.
As a consequence of the use of pull-down lists of existing values, a user is forced to build the model hierarchicaly, in the order compartment>species>parameter>reaction etc., minimizing the risk of syntactic errors. An exception is the use of the graphical MathML editor (see below).
All SBML elements can be annotated in a controled manner  using the Resource Description Framework (RDF) . The editor can parse each annotation element to see if it contains, at the top level, an RDF element, and that this RDF element complies with the format cited above. Additional annotation is entered through a dialog that displays predefined resources. Those predefined resources are stored in an XML file provided with the distribution (in the main installation folder), and that can be extended by the user. In addition, custom resources can be added directly as free text.
The definition of a resource in the XML file follows the syntax described below:
resource name="Gene Ontology"
elements="model compartment species reaction event algebraicRule assignmentRule rateRule"
The only mandatory fields are name, uri and elements. The attribute elements is a list of the different SBML elements with which the resource can be associated. The attribute name is the only information displayed to the user. The uri is a stable string representing the data type, as described in the MIRIAM standard . MIRIAM, standing for Minimal Information Requested In the Annotation of Models, is an effort to standardize the minimal metadata so that different groups can collaborate on annotating and curating computational models in biology. On the contrary of the uri, location and action are dependent of the user configuration and could vary from one user to the other. The idInputHelper and idPattern fields help in defining a valid identifier.
A number of rules must be checked to be sure of the complete validity of the SBML model. A web page regrouping all these rules has been created to help software developers in checking all of them . We implemented some of these consistency checks in SBMLeditor, but most of them are performed using the function checkConsistency of libSBML.
System Biology Workbench (SBW)
Problems and future developments
The XML parsing using DOM is not efficient for large files. SBMLeditor was not originally conceived to manipulate large models. Since large models already exist and will become more frequent (in particular when model composition will become mainstream), we have to think about some way to help their editing.
More methods need to be developed to check the consistency of the model. Some will be developed within libSBML, while some will have to be included in the editor itself.
Support for the forthcoming SBML Level 2 Version 2 has to be completed.
Contextual help has to be added for each dialog, that will include both the relevant part of the SBML specification and the SBMLeditor specific help.
Support for the Systems Biology Ontology (SBO)  has to be implemented.
SBMLeditor is a fully functional editor for modellers who want to develop a model de novo in SBML, but also for scientists who need to read an SBML model generated by another tool. As an example, SBMLeditor is used by the curators of BioModels Database  to encode models, or to curate models submitted to the database by third-parties. SBMLeditor allows users to develop a model more quickly and with less errors than a generic XML editor.
Availability and requirements
The SBMLeditor is distributed the GNU General Public License (GPL). Distribution for several environments including the code source and some data can be downloaded at http://www.ebi.ac.uk/compneur-srv/SBMLeditor.html.
This work was supported by the European Molecular Biology Laboratory. Authors are grateful to Alex Golubev and Compugen for the development of SBW support.
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