Cytoscape

Stewart MacArthur2010

Visualization tool for network dataFree & open sourceCross-Platform - JavaAdditional features available via Plugins

Large development community Current Version 2.6.3Original reference cited 1323 times (since 2003)

What is Cytoscape?"Cytoscape is an open source bioinformatics software platform for visualizing molecular interaction networks and integrating these interactions with gene expression profiles and other state data."

Network Visualization

A interacts BB interacts CB interacts DB interacts EC interacts BD interacts D

Core Functions

Supports standard network and annotation file formats: SIF - Simple Interaction Format GML - Graph Modelling Language XGMML -eXtensible Graph Markup and Modeling Language BioPAX - Biological Pathway Exchange PSI-MI - Proteomics Standards Initiative - Molecular Interaction SBML - Systems Biology Markup Language OBO - Open Biomedical Ontologies

.. .. Also Any delimited file (tab, comma etc) Excel

Core Functions

Search - Search nodes and edges with quick search or complex queries

Filter - Filter data based on any current data, number of interactions, shared nodes, expression level etc.

Layout - Display networks in 2D with a variety of algorithms

VizMapper - Customise display with colour mapping, e.g node colour to fold change or p-value, Edge width to significance etc.

Core Functions

Layouts

VizMapper

Plugins

Cytoscape's core functionality is extended by plugins

Data retrieval from databasesAgilent Literature Search NCBIPathway CommonsIntACTBioNet Builder

Data analysis

BiNGOClueGO VistaClaraMCODE

Data Retrieval: as a client for external databases

Protein Interaction database from EMBL-EBI

Protein Interactions from Entrez Gene

Collection of databases

Data management system, e.g. annotation

External datbases can be searched by gene or gene list, and results from multiple databases merged.

Data Analysis: BiNGO Biological Network Gene Ontology 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. PubMed

BiNGOBiological Network Gene Ontology

Plugin: BiNGOBiological Network Gene Ontology

A visualization plugin for exploratory analysis of multi-experiment microarray studies

Plugin: VistaClara

Merge Networks

Network Analysis Plugins

MCODE - Finds clusters (highly interconnected regions) in a network. jActiveModules - Finds clusters with unexpectedly high levels of differential expression and correlated expression patterns across multiple conditions

Network Analyser - Computes specific parameters describing the network topology, such as centralization, average number of neighbors and Heterogeneity etc.

MCODEAn automated method for finding molecular complexes in large protein interaction networks.Bader GD, Hogue CW. BMC Bioinformatics . 2003 Jan 13;4(1):2.

Finds clusters, highly interconnected regions, in networksDepending on context these could be:

protein complexessub-networkshigh-evidence interactions

jActiveModules

finds active subnetworksclusters with significant changes in expression over subsets of conditions

References

Integration of biological networks and gene expression data using Cytoscape Cline et. al. Nature Protocols 2, - 2366 - 2382 (2007) Cytoscape: a software environment for integrated models of biomolecular interaction networks Shannon et. al. Genome Research 13(11):2498-504. (2003) Exploring biological networks with Cytoscape software.Curr Protoc Bioinformatics. 2008 Sep;Chapter 8:Unit 8.13.

Practical

Macrophages Stimulated with LPS Expression arrays - time courseClustering revealed group of earlycoexpressed transcription factors (cluster 6)Motif Finding - ATF3 binding sites in promotersATF3 Network showed interactions withNF-KB complex (light green)Motif Finding - ATF3 and NF-KB sites in cluster2 (expressed later)Cytokines IL6 and IL12b enriched for sites near promoterLPS -> ATF3 -> Cytokines, Previously unknown interactions

Case Study

Further Information

Cytoscape.org Cytoscape Wiki

User Manual Tutorials

Bioinformatics Core Wiki - Tutorial

Network Analyser

Computing topological parameters of biological networks.Assenov, Y et. al . Bioinformatics , 24(2):282-284, 2008

analysis of biological networks calculates network topology parametersdiameter of a networkaverage number of neighborsnumber of connected pairs of nodes

distributions of network parametersnode degreesaverage clustering coefficientstopological coefficientsshortest path lengths

Plugin API and Scripting

API and tutorials for plugin development in JavaScripting support for Python,Ruby, Javascript and Groovy Scripting can:

add new functions automate analysislink new data sourcesexport information test algorithms beforecreating plugin

Other PluginsGenePro Cerebral

Cerebral

Plugin: Agilent Literature Search

Data Retrieval Plugin: Agilent Literature SearchMeta-search Tool Automatic query of text based search engines e.g. PubMed, OMIM, USPTO