Bioinformatics Advance Access originally published online on June 6, 2007
Bioinformatics 2007 23(16):2193-2195; doi:10.1093/bioinformatics/btm304
The MiSink Plugin: Cytoscape as a graphical interface to the Database of Interacting Proteins
UCLA-DOE Institute for Genomics & Proteomics, Departments of Chemistry & Biochemistry & Biological Chemistry, Howard Hughes Medical Institute, Box 951570, UCLA, Los Angeles, CA 90095, USA
*To whom correspondence should be addressed.
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ABSTRACT |
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 TOP ABSTRACT 1 INTRODUCTION2 OVERVIEW3 CONFIGURATIONACKNOWLEDGEMENTSREFERENCES |
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Summary: The MiSink Plugin converts Cytoscape, an open-source bioinformatics platform for network visualization, to a graphical interface for the database of interacting proteins (DIP: http://dip.doe-mbi.ucla.edu). Seamless integration is possible by providing bi-directional communication between Cytoscape and any Web site supplying data in XML or tab-delimited format.
Availability: MiSink is freely available for download at http://dip.doe-mbi.ucla.edu/Software.cgi
Contact: lukasz{at}mbi.ucla.edu
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1 INTRODUCTION |
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TOPABSTRACT1 INTRODUCTION2 OVERVIEW3 CONFIGURATIONACKNOWLEDGEMENTSREFERENCES |
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Genome-wide studies of proteins interactions, particularly large-scale two-hybrid and mass-spectrometric studies (Causier, 2004; Dziembowski and Seraphin, 2004; Parrish et al., 2006 for review) have rapidly increased the amount of data available from interaction databases such as DIP (Salwinski et al., 2004), IntAct (Hermjakob et al., 2004b) and many others (Rohl et al., 2006). However, interactive access and analysis of the interaction data remain difficult because of the text-oriented, static nature of Web interfaces which are often centered on a single protein at a time. As a result, gathering and analyzing information about entire sets of functionally related proteins can be a tedious task. It often involves downloading and off-line processing of numerous data files which in the end are transformed into a format recognizable by Cytoscape (Shannon et al., 2003). The data pre-processing step often requires hands-on programming experience and thorough knowledge of diverse data exchange formats. The process of data import can be partially simplified by using Java Web Start application-deployment technology, as demonstrated, e.g. on the Reactome site (Vastrik et al., 2007; URL: http://www.reactome.org). However, even in this case, preassembled, large datasets can be loaded into Cytoscape only one at a time. Thus, merging of the data still requires multiple Cytoscape runs and time-consuming removal of the data not needed in each particular case. Either way, the procedure results in slowed down analysis and discovery of the underlying biological processes.
These limitations are addressed by MiSink Plugin—an add-on module to Cytoscape which converts this standalone, protein-network centered bioinformatic platform for data integration, visualization and analysis into an enhanced interface to the DIP database (URL: http://dip.doe-mbi.ucla.edu). Besides accepting data in the MIF 2.5 format, as currently provided by DIP and other interaction databases, MiSink can be easily customized to accept practically arbitrary XML and tab-delimited text files. Thus, especially when accompanied by straightforward modifications to the already existing Web sites, it can serve as the foundation of a generic, network-based framework for integration of diverse data from numerous other databases.
MiSink does not strive to create any system of global identifiers in an attempt to unify the constantly growing body of biological data but rather serves a tool that can be used by a group of collaborating databases to unify access to the data they provide. Thus, in contrast to the currently available alternatives, such as cPath (Cerami et al., 2006), PIANA (Aragues et al., 2006) or BioNetBuilder (URL: http://err.bio.nyu.edu/cytoscape/bionetbuilder/), MiSink does not require deployment of local mirrors of the community databases nor relies on a third party integrators providing unified, but often delayed, access to the diverse resources on the Web. Instead, it encourages community cooperation by enabling direct data transfer utilizing MiSink dedicated links provided on MiSink/Cytoscape-enabled Web sites.
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2 OVERVIEW |
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TOPABSTRACT1 INTRODUCTION2 OVERVIEW3 CONFIGURATIONACKNOWLEDGEMENTSREFERENCES |
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MiSink Plugin adds new functionality to Cytoscape by providing bi-directional, interactive communication and data exchange between the Cytoscape platform and an arbitrary Web-based database. This goal is attained by converting a running copy of the Cytoscape program into a minimal HTTP server/client that, in response to queries issued by a local Web browser requests interaction data from a remote database. The data, provided in XML format, is processed by the MiSink Plugin according to user-defineable rules and incorporated into current Cytoscape interaction network.
The new functionality is demonstrated on the Web site of the Database of Interacting Proteins (DIP: http://dip.doe-mbi.ucla.edu). The ‘cDIP’ links (Fig. 1A, Step I) were recently added to the site to provide information about the interactions shown on individual pages in the community-supported MIF 2.5 format (Hermjakob et al., 2004a). Clicking on the cDIP icons results in loading of the corresponding fragment of the protein interaction network into Cytoscape (Fig. 1A, Step I). The incoming file contains basic annotation of the proteins and interactions, including cross-references to the relevant protein and interaction data repositories. These cross-references are, in turn, available within Cytoscape through a set of context-sensitive pop-up menus. They can be used to connect to the relevant databases to obtain up-to date information on the proteins and interactions of interest (Fig. 1A, Step II). Some of the links within the context-sensitive menus lead back to the DIP site (Fig. 1A, Step III) thus closing the circle needed for the return back to the DIP site. It is thus possible, by seamlessly moving back and forth between Cytoscape and a properly modified Web site, such as DIP, to travel along an arbitrary path within the interaction network.
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The data imported during this process into Cytoscape can then be saved locally and used for further analysis.
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3 CONFIGURATION |
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TOPABSTRACT1 INTRODUCTION2 OVERVIEW3 CONFIGURATIONACKNOWLEDGEMENTSREFERENCES |
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The behavior of the MiSink plugin is controlled by a single XML-based file describing a set of filters used to extract the relevant information from the incoming data and to store it within Cytoscape data structure. The file utilizes XPath expression language (http://www.w3.org/TR/xpath) to identify elements of the incoming file that correspond to individual proteins, interactions and their annotation. For example, the configuration file shown in Figure 1B provides all information that is needed to interpret key data in the incoming MIF 2.5 files, such as these returned by the dedicated links on the DIP Web site. Here, the xpath attributes within <node>, <edge> and <vertex> elements identify locations within an incoming MIF file that contain information about individual proteins and interactions. <attribute> elements provide, also as an XPath expression, information about location of data to be used for annotation as well as expressions to be used to construct links to the cross-reference databases.
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ACKNOWLEDGEMENTS |
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TOPABSTRACT1 INTRODUCTION2 OVERVIEW3 CONFIGURATIONACKNOWLEDGEMENTSREFERENCES |
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We thank DOE (grant DE-FC03-02ER63421) and NIH (grant 1 R01 GM071909) for support.
Conflict of Interest: none declared.
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FOOTNOTES |
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Associate Editor: Olga Troyanskaya
Received on March 28, 2007; revised on May 21, 2007; accepted on May 31, 2007
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REFERENCES |
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TOPABSTRACT1 INTRODUCTION2 OVERVIEW3 CONFIGURATIONACKNOWLEDGEMENTSREFERENCES |
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Aragues R, et al. PIANA: protein interactions and network analysis. Bioinformatics (2006) 22:1015–1057.
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Dziembowski A, Seraphin B. Recent developments in the analysis of protein complexes. FEBS Lett (2004) 556:1–6.[CrossRef][Web of Science][Medline]
Hermjakob H, et al. The HUPO PSI's molecular interaction format–a community standard for the representation of protein interaction data. Nat. Biotechnol (2004a) 22:177–183.[CrossRef][Web of Science][Medline]
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Parrish JR, et al. Yeast two-hybrid contributions to interactome mapping. Curr. Opin. Biotechnol (2006) 17:387–393.[CrossRef][Web of Science][Medline]
Rohl C, et al. Cataloging the relationships between proteins: a review of interaction databases. Mol. Biotechnol (2006) 34:69–93.[CrossRef][Web of Science][Medline]
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Shannon P, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res (2003) 13:2498–2504.
Vastrik I, et al. Reactome: a knowledge base of biologic pathways and processes. Genome Biol (2007) 8:R39.[CrossRef][Medline]
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