Bioinformatics Advance Access originally published online on October 11, 2006
Bioinformatics 2006 22(23):2966-2967; doi:10.1093/bioinformatics/btl520
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Supporting the SBML layout extension
Keck Graduate Institute, 535 Watson Dr Claremont CA 91711, USA
*To whom correspondence should be addressed.
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ABSTRACT |
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 TOP ABSTRACT 1 INTRODUCTION2 SBMLSUPPORTLAYOUT: READING AND...3 SBWAUTOLAYOUT: GENERATING...REFERENCES |
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Motivation: Researchers studying large or complex biochemical networks would benefit from the ability to automatically create lucid visualizations and store them in a portable and widely accepted format.
Summary: Two modules, SBMLSupportLayout and SBWAutoLayout, support reading, creating, manipulating and writing layout information for biochemical models. SBMLSupportLayout can read, update, add and render model layout information. SBWAutoLayout can automatically layout models, graphically manipulate model layout and generate layout information for models without layout information.
Availability: SBMLSupportLayout and SBWAutoLayout are distributed with the Systems Biology Workbench (SBW), which can be downloaded from http://www.sys-bio.org. Additionally, their visualization and layout capabilities are available online at http://www.sys-bio.org/Layout. Both modules run on Win32, Linux and the Mac OS X version is forthcoming.
Contact: fbergman{at}kgi.edu
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1 INTRODUCTION |
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TOPABSTRACT1 INTRODUCTION2 SBMLSUPPORTLAYOUT: READING AND...3 SBWAUTOLAYOUT: GENERATING...REFERENCES |
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The Systems Biology Markup Language (SBML) (Hucka et al., 2003) is a format for storing information about biochemical kinetic models and is currently supported by over one hundred software systems (www.sbml.org). Many users wish to visualize biochemical models as graphical networks and the upcoming SBML Level 3 will include a layout extension (Gauges et al., 2006). The stored layout information includes the layout dimensions, positions and dimensions of compartments, species and text and positions and line styles of reactions. Until SBML Level 3 is finalized, this SBML extension is stored in a mechanism called an annotation. Of further interest is the Systems Biology Graphical Notation (SBGN), which attempts to define a rendering standard that complements the layout standard (Kitano et al., 2005).
The Systems Biology Workbench (SBW) (Sauro et al., 2003) is both a collection of modules for analyzing, visualizing and simulating biochemical models and a framework for reusing its modules in other applications. SBW is available freely under the BSD license and all of its modules read and write SBML. To provide support for the emerging SBML Layout Extension, the SBMLSupportLayout and SBWAutoLayout modules were added to SBW. Both modules have graphical interfaces for users and expose their core layout functionalities for use in other SBW-enabled applications. SBMLSupportLayout and SBWAutoLayout were written in C# and run on Windows and Linux, while the Mac versions are currently being ported.
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2 SBMLSUPPORTLAYOUT: READING AND WRITING LAYOUT INFORMATION |
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TOPABSTRACT1 INTRODUCTION2 SBMLSUPPORTLAYOUT: READING AND...3 SBWAUTOLAYOUT: GENERATING...REFERENCES |
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The SBMLSupportLayout module supports reading and modifying existing layout information in SBML or adding layout information to SBML. Based on the SBML Layout Extension (Gauges et al., 2006), we developed a rendering extension that specifies additional rendering information, such as color, fonts, gradients and grouping information. The module can render layout information and save bitmap images of the model. SBMLSupportLayout allows all SBW modules to take advantage of a unified layout interface. Finally, because the SBML Layout Extension is not yet widely adopted, the module provides additional support for JDesigner (Sauro et al., 2003) and CellDesigner (Kitano et al., 2005) models, as they are the most commonly used graphical model editors.
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3 SBWAUTOLAYOUT: GENERATING LAYOUT |
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TOPABSTRACT1 INTRODUCTION2 SBMLSUPPORTLAYOUT: READING AND...3 SBWAUTOLAYOUT: GENERATING...REFERENCES |
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SBWAutoLayout addresses the arduous task of manually attempting to untangle large or complex models by automatically creating coherent layouts for models. Additionally, SBWAutoLayout generates the necessary layout information for models lacking layout information, which are then saved in SBML files that conform to the SBML Layout Extension specification. The graphical interface gives the user the opportunity to visually explore models, manually adjust models and customize the automatic layout options in addition to creating and saving layouts for models. Developers of other SBW-enabled applications can use SBWAutoLayout's automatic layout and SBML Layout Extension generation capabilities. For example, JDesigner (Sauro et al., 2003) and the online SBML Layout Viewer (http://www.sys-bio.org/Layout) use this module for their layout capabilities. Jarnac scripts (Sauro, 2000) can also be submitted to SBWAutoLayout for automatic layout and rendering.
3.1 Graphical interface
From SBWAutoLayout's interface, users can work with their models by importing and exporting SBML files or by using the SBW menu, which allows the user to transfer a model between SBW-enabled applications. The model's connections are Bezier curves that are calculated automatically, including the splaying of any forked or looped connections to make them perceptible, Figure 1a and b. To examine the model, users can zoom, pan or select which node to center on the screen. Nodes can be aliased by clicking on an individual node or by selecting to alias all nodes with a degree above a specified value, which aids in simplifying complex models, Figure 1c.
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The program can automatically generate a layout for the network, where the user can adjust the layout generation parameters, such as changing the strength of gravity and the optimal distance between nodes. Additionally, users can lock individual nodes or connections so they will not be affected by layout generation. Finally, users can freely move the model's nodes and connections while the program maintains the connection's coherence by automatically recalculating all associated curves.
3.2 Loading and saving models
SBWAutoLayout relies on two other SBW modules: the Network Object Model (NOM) (Sauro et al., 2003) and SBMLSupportLayout. The NOM reads SBML and returns information about the model, such as the number, identifiers and names of compartments, species and reactions. If the model has no layout information, SBWAutoLayout requests the model information from the NOM and then creates all necessary layout information for the model. If the model already has layout information, SBWAutoLayout requests some model information from the NOM and requests the remaining model information and layout information from the SBMLSupportLayout.
To save layout information SBWAutoLayout uses SBMLSupportLayout to generate the SBML. If the SBML already contained layout information, SBMLSupportLayout is called to update the existing layout information. If the SBML did not contain layout information, SBWAutoLayout supplies the necessary layout information to SBMLSupportLayout to create SBML. Finally, the SBML is written to a file. Additionally, images can be saved separately in raster (JPG, PNG, BMP) or vector (PS) formats.
3.3 Creating a layout for the networks
The basis for SBWAutoLayout's layout algorithm is the force-directed placement algorithm from Fruchterman and Reingold, 1991, which we modified to accommodate the complexities often present in models of biochemical networks. For nodes of different sizes, the optimal distance between them is adjusted to prevent overlap. Densely connected regions are prevented from collapsing by forcing the nodes farther apart. Gravity was added to the algorithm to attract any disconnected parts of the model to one another, thereby minimizing extraneous space between the parts of the model. Magnetism aligns the arrows indicating the direction of a reaction with multiple products or reactants by moving the reactants closer to one another and moving the products closer to one another.
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Acknowledgments |
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This work was supported by generous grants from the National Science Foundation Grant No. 0432190 (A.D.) and the DOE GTL Program (F.T.B.).
Conflict of Interest: none declared.
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FOOTNOTES |
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Associate Editor: Nikolaus Rajewsky
Received on August 11, 2006; revised on October 6, 2006; accepted on October 8, 2006
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REFERENCES |
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TOPABSTRACT1 INTRODUCTION2 SBMLSUPPORTLAYOUT: READING AND...3 SBWAUTOLAYOUT: GENERATING...REFERENCES |
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Elowitz, M.B. and Leibler, S. (2000) A synthetic oscillatory network of transcriptional regulators. Nature, 403, 335–338[CrossRef][Medline].
Fruchterman, T.M.J. and Reingold, E.M. (1991) Graph drawing by force-directed placement. Software, Practice and Experience, 21, 1129–1164[CrossRef].
Gauges, R., et al. (2006) A model diagram layout extension for SBML. Bioinformatics, 22, 1879–1885
Hucka, M., et al. (2003) The systems biology markup language (SBML): a medium for representation and exchange of biochemical network models. Bioinformatics, 19, 524–531
Kholodenko, B.N. (2000) Negative feedback and ultrasensitivity can bring about oscillations, in the mitogen-activted protein kinase cascades. Eur. J. Biochem, 267, 1583–1588[Web of Science][Medline].
Kitano, H. (2005) Using process diagrams for the graphical representation of biological networks. Nat. Biotechnol, . 23, 961–966[CrossRef][Web of Science][Medline].
Sauro, H.M. (2000) JARNAC: a system for interactive metabolic analysis. In Hofmeyr, J.-H.S., Rohwer, J.M., Snoep, J.L. (Eds.). Animating the Cellular Map, , Stellenbosch Stellenbosch University Press, pp. 221–228.
Sauro, H., et al. (2003) Next generation simulation tools: the Systems Biology Workbench and BioSPICE integration. OMICS, 7, 355–72[CrossRef][Medline].
Teusink, B. (2000) Can yeast glycolysis be understood in terms of in vitro kinetics of the constituent enzymes? Testing biochemistry. Eur. J. Biochem, . 267, 5313–5329[Web of Science][Medline].
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