visualizing networks: cytoscapebarc.wi.mit.edu/education/hot_topics/cytoscape/cytoscape.pdf ·...
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Visualizing Networks: Cytoscape
Prat Thiru
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Outline• Introduction to Networks
• Network Basics
• Visualization
• Inferences
• Cytoscape
• Demo
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Why (Biological) Networks?
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Networks: An Integrative Approach
Zvelebil, M., and Baum, O.J. Understanding Bioinformatics ch. 17Barabasi, A., and Oltavi, Z. Life's Complexity Pyramid Science Science 298:763‐764 (2002)
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Examples
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What are Networks?• Representation of relationships
– Physical Interactions
– Regulatory Interactions
– Genetic Interactions
– Similarity Relationships
6Bader, G.D., et al. How to visually interpret biological data using networks Nature Biotechnology 27:921‐924 (2009)
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Network Basics• Graphs with nodes (or vertices) and edges
• Nodes: Proteins, Genes, RNA, or other
biomolecule
• Edges: nature of interaction
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Network Basics• Directed vs Undirected Network• Degree (k): number of links the node
has to other nodes– Incoming degree kin
– Outgoing degree kout
• Shortest Path: fewest links or edges between two nodes
A
D
B
C
E
F
Barabasi, A., and Oltavi, Z. Network Biology: Understanding the Cell’s Functional Organization Nature Reviews Genetics 5:101‐113 (2004)8
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Network Basics: Biological Network Properties
• Scale‐free– degree distribution follows the
power‐law– few highly interconnected nodes
• Small‐world– most nodes can be reached from
every other by a small number of steps
• Modular– group of physically or functionally
linked molecules that work together to achieve a distinct function
Barabasi, A., and Oltavi, Z. Network Biology: Understanding the Cell’s Functional Organization Nature Reviews Genetics 5:101‐113 (2004)9
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Network Basics: Motifs• A pattern that occurs more often than in randomized networks
• eg. feed‐forward loop
Milo, R., et al. Network Motifs: Simple Building Blocks of Complex Networks Science 298:824‐287 (2002)10
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Visualization: Layout• Use layout algorithm
– Force‐directed– Spring‐embedded
• Most visualization software contains many layout options
• Large networks with many edges/nodes results in hairball – breakdown the network into smaller parts.
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Visualization: Features• Draw edges and nodes with different visual features (eg. shapes, colors, sizes, edge thickness)
• Examples:– Node color to represent cellular localization
– Protein colored based on similar function
– Edge thickness based on correlation data
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Visualization: Layout and Features
Bader, G.D., et al. How to visually interpret biological data using networks Nature Biotechnology 27:921‐924 (2009)13
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Visualization: Layout and Features
Gehlenborg, N., et al. Visualization of omics data for systems biology Nature Methods 7:S56‐S68 (2010)14
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Inferences of Neworks• Protein Function Prediction
– guilt by association– Infer protein function based on interactions– Neighboring nodes should be annotated
• Highly Interconnected Nodes– hubs– dense cluster => characteristic of protein complexes or pathways
– Indispensable• Global System Relationships
Bader, G.D., et al. How to visually interpret biological data using networks Nature Biotechnology 27:921‐924 (2009) 15
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Limitations• Difficult to capture temporal and concentration information in a static representation
• All relationships might not be represented in pairwise edges
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Cytoscape• Freely available open source Java‐based software for
visualizing and analyzing network• Made public in July 2002• Latest version is 2.7.0• Win/Mac/Linux• Easy to install• 918 citations (Apr 2010)• Core functions:
– network layout and querying– expression profile integration– linking of network to different databases
• Additional functionality by pluginshttp://www.cytoscape.org/plugins2.php
CytoscapeConsortium
Shannon, P., Markiel, A., Ozier, O., Baliga, N.S., Wang, J.T., Ramage, D., Amin, N., Schwikowski, B., Ideker, T. Cytoscape: A Software Environment for Integrated Models of Biomolecular Interaction Networks Genome Research 13:2498‐504 (2003)
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Cytoscape
File Formats Web Service Clients Visualization
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Network Visualization SoftwareName Cost Description URL
BioLayout Express 3D FreeGeneration and cluster analysis of networks with 2D/3D visualization
http://www.biolayout.org/
BiologicalNetworks FreeAnalysis suite; visualizes networks and heat map; abundance data
http://www.biologicalnetworks.org/
Cytoscape FreeNetwork analysis; extensive list of plug‐ins for advanced visualization
http://www.cytoscape.org/
Ingenuity Pathways $Full analysis suite; network and pathway a
http://www.ingenuity.com/
Medusa Free Basic network visualization tool http://coot.embl.de/medusa/
GeneGO $Full analysis suite; network and pathway visualizations
http://www.genego.com/
Ondex FreeIntegrative workbench: large network visualizations; abundance data
http://www.ondex.org/
Osprey FreeTool for visualization of interaction networks
http://tinyurl.com/osprey1/
Pajek FreeGeneric network visualization and analysis tool
http://pajek.imfm.si/
ProViz FreeSoftware for visualization and exploration of interaction networks
http://tinyurl.com/proviz/
Gehlenborg, N., et al. Visualization of omics data for systems biology Nature Methods 7:S56‐S68 (2010)Schneider, R., et al. A survey of visualization tools for biological network analysis BMC: BioData Mining I:1‐12 (2008)
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Visualization Tools Comparison
Cline, M.S., et al. Integration of biological networks and gene expression data using Cytoscape Nature Protocols 2:2366‐2382 (2007)20
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Cytoscape Example
Emili, A., et al. Pathway analysis of dilated cardiomyopathy using global proteomic profiling and enrichment maps. Proteomics 10:1316‐1327 (2010)
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Cytoscape Example
Emili, A., et al. Pathway analysis of dilated cardiomyopathy using global proteomic profiling and enrichment maps. Proteomics 10:1316‐1327 (2010)
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Pathway Databases• BioCyc
http://biocyc.org/• Kyoto Encyclopedia of Genes and Genomes (KEGG)
http://www.genome.jp/kegg/• Pathguide
http://www.pathguide.org/• Reactome
http://www.reactome.org/
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Demo• Uploading Network
• Adding annotation
• Viewing gene expression data
• BiNGO plugin