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Bioinformatics Advance Access originally published online on June 6, 2007
Bioinformatics 2007 23(16):2193-2195; doi:10.1093/bioinformatics/btm304
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© The Author 2007. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

The MiSink Plugin: Cytoscape as a graphical interface to the Database of Interacting Proteins

Lukasz Salwinski and David Eisenberg *

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.


   ABSTRACT
TOP
 ABSTRACT
1 INTRODUCTION
 2 OVERVIEW
 3 CONFIGURATION
 ACKNOWLEDGEMENTS
 REFERENCES
 

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


   1 INTRODUCTION
TOP
 ABSTRACT
 1 INTRODUCTION
2 OVERVIEW
 3 CONFIGURATION
 ACKNOWLEDGEMENTS
 REFERENCES
 
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.


   2 OVERVIEW
TOP
 ABSTRACT
 1 INTRODUCTION
 2 OVERVIEW
3 CONFIGURATION
 ACKNOWLEDGEMENTS
 REFERENCES
 
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.


Figure 1
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  		Fig. 1. MiSink Plugin features. (A) Traversing protein interaction networks using MiSink-enabled Web site (DIP: http://dip.doe-mbi.ucla.edu) and Cytoscape. Three additional operations are possible: (i) importing interaction data into Cytoscape by following the dedicated links provided on the DIP Web pages; (ii) retrieving information about protein interactions by using the context sensitive pop-up menus option leading back to the DIP site and (iii) retrieving the most recent annotation data by following the links leading from the context sensitive pop-up menus to the primary annotation databases. (B) The default configuration file of the MiSink Plugin, sufficient for importing of the most essential information from MIF 2.5 files into Cytoscape. The compulsory elements, marked in blue, specify nodes and edges of the resulting Cytoscape network. The corresponding locations within the incoming file are specified with XPath expressions used within all XML attributes marked in red. The optional <attribute> elements are used to specify additional information, including external references, to be imported from the incoming file. The refURL attributes, if present, provide information about the location of the external references on the Web.

 
The data imported during this process into Cytoscape can then be saved locally and used for further analysis.


   3 CONFIGURATION
TOP
 ABSTRACT
 1 INTRODUCTION
 2 OVERVIEW
 3 CONFIGURATION
ACKNOWLEDGEMENTS
 REFERENCES
 
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.


   ACKNOWLEDGEMENTS
TOP
 ABSTRACT
 1 INTRODUCTION
 2 OVERVIEW
 3 CONFIGURATION
 ACKNOWLEDGEMENTS
REFERENCES
 
We thank DOE (grant DE-FC03-02ER63421) and NIH (grant 1 R01 GM071909) for support.

Conflict of Interest: none declared.


   FOOTNOTES
 
Associate Editor: Olga Troyanskaya

Received on March 28, 2007; revised on May 21, 2007; accepted on May 31, 2007

   REFERENCES
TOP
 ABSTRACT
 1 INTRODUCTION
 2 OVERVIEW
 3 CONFIGURATION
 ACKNOWLEDGEMENTS
 REFERENCES
 

    Aragues R, et al. PIANA: protein interactions and network analysis. Bioinformatics, ( (2006) ) 22, : 1015–1057.[Abstract/Free Full Text].

    Causier B. Studying the interactome with the yeast two-hybrid system and mass spectrometry. Mass Spectrom. Rev, ( (2004) ) 23, : 350–367.[CrossRef][ISI][Medline].

    Cerami EG, et al. cPath: open source software for collecting, storing, and querying biological pathways. BMC Bioinformatics, ( (2006) ) 7, : 497.[CrossRef][Medline].

    Dziembowski A, Seraphin B. Recent developments in the analysis of protein complexes. FEBS Lett, ( (2004) ) 556, : 1–6.[CrossRef][ISI][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][ISI][Medline].

    Hermjakob H, et al. IntAct: an open source molecular interaction database. Nucleic Acids Res, ( (2004b) ) 32, : D452–D455.[Abstract/Free Full Text].

    Parrish JR, et al. Yeast two-hybrid contributions to interactome mapping. Curr. Opin. Biotechnol, ( (2006) ) 17, : 387–393.[CrossRef][ISI][Medline].

    Rohl C, et al. Cataloging the relationships between proteins: a review of interaction databases. Mol. Biotechnol, ( (2006) ) 34, : 69–93.[CrossRef][ISI][Medline].

    Salwinski L, et al. The Database of Interacting Proteins: 2004 update. Nucleic Acids Res, ( (2004) ) 32, : D449–D451.[Abstract/Free Full Text].

    Shannon P, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res, ( (2003) ) 13, : 2498–2504.[Abstract/Free Full Text].

    Vastrik I, et al. Reactome: a knowledge base of biologic pathways and processes. Genome Biol, ( (2007) ) 8, : R39.[CrossRef][Medline].


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