Active Pathways

Brief Project Description

Visualization and analysis of pathways and expression data.

Gene expression profiling is broadly used to identify genes modulated in biological processes. To gather a better understanding at the system level, available analysis methods can be used to identify (a) functional sets (e.g. DAVID, GSEA) or (b) network modules (e.g. Active Modules) enriched by modulated genes. Functional sets are often derived from Gene Ontology annotations, whereas networks capture pairwise gene relations such as protein physical interactions. Tools are also available to color static pathway maps according to gene expression (e.g. GenMAPP).

The Active Pathways project aims at integrating the two enrichment analysis strategies for BioPAX-encoded pathways within the Cytoscape network visualization environment. Pathways are queried for set enrichment using GSEA; the user can browse the pathway set hierarchy and generate different network views of selected pathways. The step network displays pathway steps and next-step relations, providing a skeleton view of information/matter fluxes. The gene network displays pairwise gene interactions mapped from more complex BioPAX interactions (following the BioPAX to SIF conversion rules defined in Pathway Commons). The BioPAX entity network displays gene products, small molecules, interactions, complexes as entities and their mutual relations as links, providing a richer but also more complex view. Every network is automatically colored according to gene expression statistics.

We are currently developing improved layout solutions for the BioPAX entity network, which will combine the logical structure of the step network with the detail of the BioPAX entity network.

Screenshots of the prototype are available at: http://baderlab.org/Software/ActivePathways.

People

Package 0.5a Release - Brief Instructions

This is the first prototype available as a plug-in, for testing in our group. What follows is a set of minimal instructions to exercise the functionality so far. As we update the package we will note changes here.

Download and Install

0. Install Cytoscape (currently testing with Cytoscape 2.7)

1. Download the applug0.5a.tgz file here: applug0.5a.tgz

2. Place the ActivePathwaysPlugin.jar and the contents of the lib directory in Cytoscape's plugins directory.

3. Place the sampleDataAP directory somewhere convenient, ideally inside Cytoscape's own sampleData directory (the plugin will look for it there automatically).

4. Launch Cytoscape and check that an "Active Pathways" sub-menu appears under the main Plugins menu.

Loading the example data sets

Some sample data is provided with the plugin to allow for easier testing and evaluation. Selecting Plugins->Active Pathways->Load Browser will bring up the data loading Wizard. To load user-supplied data, a number of files and other choices must be specified; for the example data shortcuts may be selected on the initial Wizard panel. These options will only be available once the sampleDataAP directory (or other location for the same files) has been confirmed. A location for this directory can be selected by clicking the "Choose File" button. Once done the Wizard should look something like this:

Screenshots

Browser interface in which enriched pathways may be filtered using statistics derived from (e.g.) GSEA. The hierarchical structure of pathways is shown by the tree view at left, where are enriched pathways are highlighted in green, while pathways with enriched subpathways (but not enriched overall) are highlighted in yellow. Three realizations of the same pathway (TGF-Beta signalling) generated automatically by selecting in the browser: Step network (left), BioPAX network (upper right), gene network (lower right). The same displays with node labels for pathway steps, entities, and genes respectively are shown below.