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Integration of biological networks and gene expression data using Cytoscape

Abstract

Cytoscape is a free software package for visualizing, modeling and analyzing molecular and genetic interaction networks. This protocol explains how to use Cytoscape to analyze the results of mRNA expression profiling, and other functional genomics and proteomics experiments, in the context of an interaction network obtained for genes of interest. Five major steps are described: (i) obtaining a gene or protein network, (ii) displaying the network using layout algorithms, (iii) integrating with gene expression and other functional attributes, (iv) identifying putative complexes and functional modules and (v) identifying enriched Gene Ontology annotations in the network. These steps provide a broad sample of the types of analyses performed by Cytoscape.

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Figure 1: The Cytoscape Desktop.
Figure 2: Outline of the protocol.
Figure 3
Figure 4: The steps in creating a green-to-red node color gradient.
Figure 5: JActiveModules output with the top-scoring module selected and displayed as a separate child network.
Figure 6: MCODE output, showing a densely connected network region that is a putative complex.
Figure 7: BiNGO output, analyzing the active module shown in Figure 5.

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Acknowledgements

Many research groups have developed plugins to Cytoscape and provided them for download free of charge from http://www.cytoscape.org/. These plugins represent key contributions to the overall utility of Cytoscape, and we gratefully thank the authors for their contributions. Cytoscape is developed through an ongoing collaboration between the University of California at San Diego, the University of Toronto, the Institute for Systems Biology, Memorial Sloan-Kettering Cancer Center, Institut Pasteur, Agilent Technologies and the University of California at San Francisco. Many developers have contributed to Cytoscape, and we gratefully acknowledge the contributions of former developers including Nada Amin, Mark Anderson, Richard Bonneau, Larissa Kamenkovich, Andrew Markiel, Owen Ozier, Paul Shannon, Robert Sheridan and Jonathan Wang. We thank Tero Aittikalio and Cricket Sloan for assistance with the manuscript. Funding for Cytoscape is provided by the US National Institute of General Medical Sciences of the National Institutes of Health under award number GM070743-01. Corporate funding is provided through a contract from Unilever PLC. Cytoscape contributions by G.D.B. were funded in part by Genome Canada. The BiNGO plugin was developed at the Department of Plant Systems Biology at the University of Ghent, with partial funding through the Research Foundation Flanders in Belgium.

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Authors and Affiliations

Authors

Contributions

Cytoscape development is a large community effort, with principal efforts under the direction of A.A. at Agilent Technologies; I.S. and L.H. at the Institute for Systems Biology; C.S. at Memorial Sloan Kettering Cancer Center; B.S. at Institut Pasteur; G.J.W. at Unilever; T.I. at University of California, San Diego; B.R.C. at University of California, San Francisco; and G.D.B. at University of Toronto. Every author has made significant contributions to the software, without which this protocol would not be possible. Specific contributions are as follows. E.C., B.G., G.D.B. and C.S. developed the cPath plugin. A.K., A.V. and M.C. developed the Agilent Literature Search plugin. S.M., R.I. and M.K. developed the BiNGO plugin. M.S., T.I. and R.K. developed the jActiveModules plugin. V.P., G.D.B. and C.S. developed the MCODE plugin. N.L., R.C., I.A.C., S.K., S.L., M.S., K.O. and P.-L.W. developed much of the improvements to the Cytoscape v2.5 core, including automatic loading of plugins and the VizMapper. K.H., J.M. and A.R.P. were instrumental in the usability analysis, specification and prototyping of many of these features. This protocol was written by M.S.C., M.S., A.K., S.M., C.W., G.D.B. and T.I.

Corresponding author

Correspondence to Trey Ideker.

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Sample Data for performing the protocol as a tutorial (ZIP 972 kb)

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Cline, M., Smoot, M., Cerami, E. et al. Integration of biological networks and gene expression data using Cytoscape. Nat Protoc 2, 2366–2382 (2007). https://doi.org/10.1038/nprot.2007.324

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