Biological Network Exploration with Cytoscape 3

Gang Su1, John H. Morris2, Barry Demchak3, Gary D. Bader4

1 Molecular Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, Michigan, 2 Resource for Biocomputing, Visualization, and Informatics, University of California San Francisco, San Francisco, California, 3 Department of Medicine, University of California San Diego, La Jolla, California, 4 The Donnelly Centre, University of Toronto, Toronto
Publication Name:  Current Protocols in Bioinformatics
Unit Number:  Unit 8.13
DOI:  10.1002/0471250953.bi0813s47
Online Posting Date:  September, 2014
GO TO THE FULL TEXT: PDF or HTML at Wiley Online Library

Abstract

Cytoscape is one of the most popular open‐source software tools for the visual exploration of biomedical networks composed of protein, gene, and other types of interactions. It offers researchers a versatile and interactive visualization interface for exploring complex biological interconnections supported by diverse annotation and experimental data, thereby facilitating research tasks such as predicting gene function and constructing pathways. Cytoscape provides core functionality to load, visualize, search, filter, and save networks, and hundreds of Apps extend this functionality to address specific research needs. The latest generation of Cytoscape (version 3.0 and later) has substantial improvements in function, user interface, and performance relative to previous versions. This protocol aims to jump‐start new users with specific protocols for basic Cytoscape functions, such as installing Cytoscape and Cytoscape Apps, loading data, visualizing and navigating the networks, visualizing network associated data (attributes), and identifying clusters. It also highlights new features that benefit experienced users. Curr. Protoc. Bioinform. 47:8.13.1‐8.13.24. © 2014 by John Wiley & Sons, Inc.

Keywords: Cytoscape; interactive network visualization; network analysis

     
 
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library

Table of Contents

  • Introduction
  • Basic Protocol 1: Analyzing Gene Expression Data in Cytoscape
  • Basic Protocol 2: Explore a Human Disease Network
  • Support Protocol 1: Setting Up Cytoscape
  • Support Protocol 2: Search and Install Apps
  • Guidelines for Understanding Results
  • Commentary
  • Literature Cited
  • Figures
  • Tables
     
 
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library

Materials

GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library

Figures

Videos

Literature Cited

Literature Cited
  Atkinson, H.J., Morris, J.H., Ferrin, T.E., and Babbit, P.C. 2009. Using sequence similarity networks for visualization of relationships across diverse protein superfamilies. PLoS One 4:e4345.
  Bader, G.D. and Hogue, C.W.V. 2003. An automated method for finding molecular complexes in large protein interaction networks. BMC Bioinformatics 4:2.
  Bader, G.D., Betel, D., and Hogue, C.W.V. 2001. BIND–The Biomolecular Interaction Network Database. Nucleic Acids Res. 29:242‐245.
  Barrett, T., Troup, D.B., Wilhite, S.E., Ledoux, P., Rudnev, D., Evangelista, C., Kim, I.F., Soboleva, A., Tomashevsky, M., and Edgar, R. 2007. NCBI GEO: Mining tens of millions of expression profiles—database and tools update. Nucleic Acids Res. 35:D760‐D765.
  Bastian M., Heymann S., and Jacomy M. 2009. Gephi: An open source software for exploring and manipulating networks. International AAAI Conference on Weblogs and Social Media. Association for the Advancement of Artificial Intelligence, Palo Alto, Calif.
  Batagelj, V. and Mrvar, A. 1998. Pajek‐program for large network analysis. Connections 21:47‐57.
  Chatr‐Aryamontri, A. Breitkreutz, B.J., Heinicke, S., Boucher, L., Winter, A., Stark, C., Nixon, J., Ramage, L., Kolas, N., O'Donnell, L., Reguly, T., Breitkreutz, A., Sellam, A., Chen, D., Chang, C., Rust, J., Livstone, M., Oughtred, R., Dolinski, K., and Tyers, M. 2012. The BioGRID interaction database: 2013 update. Nucleic Acids Res. 41:D816‐D823.
  Csardi, G. and Nepusz, T. 2006. The igraph software package for complex network research. InterJournal Complex Systems 1695.
  de Lichtenberg, U., Jensen, L.J., Fausbøll, A., Jensen, T.S., Bork, P., and Brunak, S. 2005. Comparison of computational methods for the identification of cell cycle‐regulated genes. Bioinformatics 21:1164‐1171.
  Doncheva, N.T., Klein, K., Domingues, F.S., and Albrecht, M. 2011. Analyzing and visualizing residue networks of protein structures. Trends Biochem. Sci. 36:179‐182.
  Doncheva, N.T., Assenov, Y., Dominiques, F.S., and Albrecht, M. 2012. Topological analysis and interactive visualization of biological networks and protein structures. Nat. Protoc. 7:670‐685.
  Dutkowski, J., Kramer, M., Surma, M.A., Balakrishnan, R., Cherry, J.M., Krogan, N.J., and Ideker, T. 2012. A gene ontology inferred from molecular networks. Nat. Biotechnol. 31:38‐45.
  Dutkowski, J., Ono, K., Kramer, M., Yu, M., Pratt, D., Demchak, B., and Ideker, T. 2014. NeXO Web: The NeXO ontology database and visualization platform. Nucleic Acids Res. 42:D1269‐D1274.
  Dutot, A., Pigne, Yoann, Dutot, Antoine, Guinand, Frederic, and Olivier, Damien. 2007. GraphStream: A tool for bridging the gap between Complex Systems and Dynamic Graphs. In Emergent Properties in Natural and Artificial Complex Systems. Satellite Conference within the 4th European Conference on Complex Systems (ECCS’2007).
  Edgar, R., Domrachev, M., and Lash, A.E. 2002. Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res. 30:207‐210.
  Fisher, D., O'Madadhain, J., Smyth, P., White, S., and Boey, Y‐B. 2005. Analysis and visualization of network data using JUNG. J. Stat. Softw. 10:1‐25.
  Franceschini, A., Szklarczyk, D., Frankild, S., Kuhn, M., Simonovic, M., Roth, A., Lin, J., Minguez, P., Bork, P., von Mering, C., and Jensen, L.J. 2013. STRING v9.1: Protein‐protein interaction networks, with increased coverage and integration. Nucleic Acids Res. 41:D808‐D815.
  Gao, J., Tarcea, V.G., Karnovsky, A., Mirel, B.R., Weymouth, T.E., Beecher, C.W., Cavalcoli, J.D., Athey, B.D., Omenn, G.S., Burant, C.F., and Jagadish, H.V. 2010. Metscape: A Cytoscape plug‐in for visualizing and interpreting metabolomic data in the context of human metabolic networks. Bioinformatics 26:971‐973.
  Gasch, A.P., Spellman, P.T., Kao, C.M., Carmel‐Harel, O., Eisen, M.B., Storz, G., Botstein, D., and Brown, P.O. 2000. Genomic expression programs in the response of yeast cells to environmental changes. Mol. Biol. Cell. 11:4241‐4257.
  Goel, R., Harsha, H.C., Pandey, A., and Prasad, T.S. 2012. Human protein reference database and human proteinpedia as resources for phosphoproteome analysis. Mol. Biosyst. 8:453‐463.
  Goh, K.‐I., Cusick, M.E., Valle, D., Childs, B., Vidal, M., and Barabási, AL. 2007. The human disease network. Proc. Natl. Acad. Sci. U.S.A. 104:8685‐8690.
  Hamosh, A., Scott, A.F., Amberger, J.S., Bocchini, C.A., and McKusick, V.A. 2005. Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders. Nucleic Acids Res. 33:D514‐D517.
  Ideker, T., Ozier, O., Schwikowski, B., and Siegel, A.F. 2002. Discovering regulatory and signalling circuits in molecular interaction networks. Bioinformatics 18:S233‐S240.
  Joshi‐Tope, G., Gillespie, M., Vastrik, I., D'Eustachio, P., Schmidt, E., de Bono, B., Jassal, B., Gopinath, G.R., Wu, G.R., Matthews, L., Lewis, S., Birney, E., and Stein, L. 2005. Reactome: A knowledgebase of biological pathways. Nucleic Acids Res. 33:D428‐D432.
  Kanehisa, M. 2002 The KEGG database. Novartis Found. Symp. 247:91‐101.
  Karnovsky, A., Weymouth, T., Hull, T., Tarcea, V.G., Scardoni, G., Laudanna, C., Sartor, M.A., Stringer, K.A., Jagadish, H.V., Burant, C., Athey, B., and Omenn, G.S. 2012. Metscape 2 bioinformatics tool for the analysis and visualization of metabolomics and gene expression data. Bioinformatics 28:373‐380.
  Kelder, T., van Iersel, M.P., Hanspers, K., Kutmon, M., Conklin, B.R., Evelo, C.T., and Pico, A.R. 2012. WikiPathways: Building research communities on biological pathways. Nucleic Acids Res. 40:D1301‐D1307.
  Kerrien, S., Aranda, B., Breuza, L., Bridge, A., Broackes‐Carter, F., Chen, C., Duesbury, M., Dumousseau, M., Feuermann, M., Hinz, U., Jandrasits, C., Jimenez, R.C., Khadake, J., Mahadevan, U., Masson, P., Pedruzzi, I., Pfeiffenberger, E., Porras, P., Raghunath, A., Roechert, B., Orchard, S., and Hermjakob, H. 2012. The IntAct molecular interaction database in 2012. Nucleic Acids Res. 40:D841‐D846.
  Lotia, S., Montojo, J., Dong, Y., Bader, G.D., and Pico, AR. 2013. Cytoscape app store. Bioinformatics 29:1350‐1351.
  Maere, S., Heymans, K., and Kuiper, M. 2005. BiNGO: A Cytoscape plugin to assess overrepresentation of gene ontology categories in biological networks. Bioinformatics 21:3448‐3449.
  Margolin, A.A., Wang, K., Lim, W.K., Kustagi, M., Nemenman, I., and Califano, A. 2006. Reverse engineering cellular networks. Nat. Protoc. 1:662‐671.
  Merico, D., Gfeller, D., and Bader, G.D. 2009. How to visually interpret biological data using networks. Nat. Biotechnol. 27:921‐924.
  Montojo, J., Zuberi, K., Rodriguez, H., Kazi, F., Wright, G., Donaldson, S.L., Morris, Q., and Bader, G.D. 2010. GeneMANIA Cytoscape plugin: Fast gene function predictions on the desktop. Bioinformatics 26:2927‐2928.
  Morris, J.H., Huang, C.C., Babbitt, P.C., and Ferrin, T.E. 2007. structureViz: Linking Cytoscape and UCSF Chimera. Bioinformatics 23:2345‐2347.
  Morris, J.H., Apeltsin, L., Newman, A.M., Baumbach, J., Wittkop, T., Su, G., Bader, G.D., and Ferrin, T.E. 2011. clusterMaker: A multi‐algorithm clustering plugin for Cytoscape. BMC Bioinformatics 12:436.
  Saito, R., Smoot, M.E., Ono, K., Ruscheinski, J., Wang, P.L., Lotia, S., Pico, A.R., Bader, G.D., and Ideker, T. 2012. A travel guide to Cytoscape plugins. Nat. Methods 9:1069‐1076.
  Scardoni, G., Petterlini, M., and Laudanna, C. 2009. Analyzing biological network parameters with CentiScaPe. Bioinformatics 25:2857‐2859.
  Shannon, P., Markiel, A., Ozier, O., Baliga, N.S., Wang, J.T., Ramage, D., Amin, N., Schwikowski, B., and Ideker, T. 2003. Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Res. 13:2498‐2504.
  Su, G., Kuchinsky, A., Morris, J.H., States, D.J., and Meng, F. 2010. GLay: Community structure analysis of biological networks. Bioinformatics 26:3135‐3137.
  Tarcea, V.G., Weymouth, T., Ade, A., Bookvich, A., Gao, J., Mahavisno, V., Wright, Z., Chapman, A., Jayapandian, M., Ozgür, A., Tian, Y., Cavalcoli, J., Mirel, B., Patel, J., Radev, D., Athey, B., States, D., and Jagadish, H.V. 2009. Michigan molecular interactions r2: From interacting proteins to pathways. Nucleic Acids Res. 37:D642‐D646.
  Turinsky, A.L. 2014. Structural Genomics. Humana Press, Totowa, New Jersey.
  Vailaya, A., Bluvas, P., Kincaid, R., Kuchinsky, A., Creech, M., and Adler, A. 2005. An architecture for biological information extraction and representation. Bioinformatics 21:430‐438.
  Yu, H. 2007. The importance of bottlenecks in protein networks: Correlation with gene essentiality and expression dynamics. PLoS Comput. Biol. 3:e59.
  Zuberi, K., Franz, M., Rodriguez, H., Montojo, J., Lopes, C.T., Bader, G.D., and Morris, Q. 2013. GeneMANIA prediction server 2013 update. Nucleic Acids Res. 41:W115‐W22.
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library