Bioinformatics Advance Access originally published online on November 16, 2007
Bioinformatics 2008 24(6):876-877; doi:10.1093/bioinformatics/btm553
BiNoM: a Cytoscape plugin for manipulating and analyzing biological networks
Institut Curie, Service de Bioinformatique, 26 rue d’Ulm, F-75248 Paris Cedex 05, France
*To whom correspondence should be addressed.
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ABSTRACT |
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 TOP ABSTRACT 1 INTRODUCTION2 METHODS AND IMPLEMENTATIONACKNOWLEDGEMENTSREFERENCES |
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BiNoM (Biological Network Manager) is a new bioinformatics software that significantly facilitates the usage and the analysis of biological networks in standard systems biology formats (SBML, SBGN, BioPAX). BiNoM implements a full-featured BioPAX editor and a method of ‘interfaces’ for accessing BioPAX content. BiNoM is able to work with huge BioPAX files such as whole pathway databases. In addition, BiNoM allows the analysis of networks created with CellDesigner software and their conversion into BioPAX format. BiNoM comes as a library and as a Cytoscape plugin which adds a rich set of operations to Cytoscape such as path and cycle analysis, clustering sub-networks, decomposition of network into modules, clipboard operations and others.
Availability: Last version of BiNoM distributed under the LGPL licence together with documentation, source code and API are available at http://bioinfo.curie.fr/projects/binom
Contact: andrei.zinovyev{at}curie.fr
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1 INTRODUCTION |
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TOPABSTRACT1 INTRODUCTION2 METHODS AND IMPLEMENTATIONACKNOWLEDGEMENTSREFERENCES |
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Importance of biological network knowledge standardization and representation is widely accepted in the systems biology community (Klipp et al., 2007). Several standards with different specialties (e.g. SBML and BioPAX) have been proposed and are actively promoted in many softwares (Stromback and Lambrix, 2005), such as CellDesigner in which the Systems Biology Graphical Notation standard (SBGN, http://sbgn.org) was proposed and implemented (Kitano et al., 2005).
The Cytoscape environment (Shannon et al., 2003) is an open-source project aimed at creating universal and flexible biological network visualization tool. It has attracted a lot of attention and collected a large and active community around it due to the possibility of extending its base functionality with user-made plugins. A number of plugins are already developed and used in practice (see the list at http://cytoscape.org). In the recent versions of Cytoscape there is an option to import BioPAX and SBML files, however, these capabilities remain limited to a simple visualization of the file content.
BiNoM (Biological Network Manager) plugin was developed to facilitate manipulating files in BioPAX and SBML formats (including CellDesigner SBML extension). BiNoM allows to read, edit, extract parts, merge and save systems biology files. Together with this function, a large set of structure analysis tools is proposed. In addition, BiNoM supports conversion of CellDesigner to BioPAX and BioPAX to SBML formats. BiNoM was used in several projects on analyzing complex biological networks [e.g. see Calzone et al., 2007].
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2 METHODS AND IMPLEMENTATION |
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TOPABSTRACT1 INTRODUCTION2 METHODS AND IMPLEMENTATIONACKNOWLEDGEMENTSREFERENCES |
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The first guiding principle of BiNoM is to provide control in Cytoscape over the content of a systems biology file without complete conversion of the file into the Cytoscape internal format. Second, BiNoM aims at dissecting and reducing the complexity of the visual network presentation with help of a number of graph structural analysis methods, some of them taking into account the biological semantics connected to the graph elements.
To access the content of a file, the BiNoM engine first maps it onto a labeled directed graph, called index. Index represents the totality of objects and their relations, but with a minimum amount of information necessary for their visual representation. The whole index is a highly connected graph that is usually not visualized explicitly. The user interacts with subgraphs extracted from the global index, called network interfaces. For example, during BioPAX import operation, BiNoM proposes to generate three standard interfaces: Reaction Network (RN), Pathway Structure (PS) and Protein–Protein interaction (PP). These subgraphs represent three different aspects of information contained in BioPAX file (see Fig. 1). For full description of a BiNoM data model, go to the BiNoM web-site.
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Starting from these subgraphs and using operations proposed by BiNoM such as copy-paste, graph merging and extracting graph parts, the user can construct his or her own arbitrary interface. Any node or edge in the interface can be assigned one or several URI attributes which BiNoM uses to access and modify the file content. To do so, the interface should be first associated to the file through BiNoM menu. After that, the user can save the whole object hierarchy or export to a file only a part of the content represented in the interface. When doing this, it is possible to merge the new information with already existing files. The BioPAX Reaction Network interface can be exported to SBML format and serve as a first draft for the creation of a pathway computational model. Any interface or the whole index can be stored as XGMML (standard labeled graph description format supported by Cytoscape) file and used later.
If the BioPAX file is huge such as a whole pathway database [e.g. Reactome (Joshi-Tope et al., 2005)], the user can use the BiNoM querying mechanism to extract part of the database and export it into a separate self-containing BioPAX file for further analysis. This mechanism enables using Cytoscape viewer and a big BioPAX file as a pathway database with a flexible interface.
Simplification and analysis of the network representation are achieved by use of the build-in library of graph analysis tools, including analysis of connected and strongly connected components, path analysis (finding shortest, suboptimal, all paths), modular decomposition of the network using node semantics, cycle analysis, subnetwork clustering and clipboard operations.
The logic implementation in the BiNoM code is completely decoupled from the Cytoscape interface. That way, BiNoM can be used as an independent biological graph analysis library. Using run-time object inspection in Java allows the reuse of BiNoM code with practically any ontology schema, even completely different from BioPAX (for example, Systems Biology Ontology). BiNoM was tested with 2.3, 2.4 and 2.5 versions of Cytoscape and with 3.* versions of CellDesigner.
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ACKNOWLEDGEMENTS |
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TOPABSTRACT1 INTRODUCTION2 METHODS AND IMPLEMENTATIONACKNOWLEDGEMENTSREFERENCES |
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This project was partly funded by the EC contract ESBIC-D (LSHG-CT-2005-518192), the PIC Bioinformatique et Biostatistiques from Institut Curie, and the Research Networks Program in Bioinformatics from the High Council for Scientific and Technological Cooperation between France and Israël.
Conflict of Interest: none declared.
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FOOTNOTES |
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Associate Editor: Trey Ideker
Received on October 5, 2007; revised on October 5, 2007; accepted on October 31, 2007
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REFERENCES |
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TOPABSTRACT1 INTRODUCTION2 METHODS AND IMPLEMENTATIONACKNOWLEDGEMENTSREFERENCES |
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Calzone L, et al. A Comprehensive Modular Map of Molecular Interactions in RB/E2F Pathway. In: Molecular Systems Biology. (2008) Available at http://bioinfo.curie.fr/projects/rbpathway.
Joshi-Tope G, et al. Reactome: a knowledgebase of biological pathways. Nucl. Acids Res (2005) 33:D428–432.
Kitano H, et al. Using process diagrams for the graphical representation of biological networks. Nat. Biotechnol (2005) 23:961–966.[CrossRef][Web of Science][Medline]
Klipp E, et al. Systems biology standards–the community speaks. Nat. Biotechnol (2007) 25:390–391.[CrossRef][Web of Science][Medline]
Shannon P, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res (2003) 13:2498–2504.
Stromback L, Lambrix P. Representations of molecular pathways: an evaluation of SBML, PSI MI and BioPAX. Bioinformatics (2005) 21:4401–4407.
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