DomainGraph: Visual Analysis of the Effects of Alternative Splicing on Protein and Domain Interaction Networks

Dorothea Emig1, Melissa S. Cline2, Thomas Lengauer1, and Mario Albrecht1

1 Department of Computational Biology and Applied Algorithmics, Max Planck Institute for Informatics, Campus E1.4, 66123 Saarbrücken, Germany

2 Department of Molecular Cell and Developmental Biology, University of California, Santa Cruz, CA 95064, USA

Biological Use Case: Visualize the domain interactions that actually form a protein interaction network. Integrate exon expression data to visualize occurrences of alternative splicing events and the impact on the interactions.

Recipe

Cytoscape version: 2.5, 2.6

Plugins to Load: DomainGraph (http://domaingraph.bioinf.mpi-inf.mpg.de)

GUI steps:

Describe each step (story), the GUI action to take, and probable remarks

Story

Action

Remarks

Create local database

Plugins -> DomainGraph -> Create Database

has to be done the first time, the db is stored locally in the Cytoscape plugins directory

Import the sample protein network and decompose it into underlying domain interactions

Plugins -> DomainGraph -> Create Domain Graph: 1. import protein interactions: select to import your own ppi network ('sample_ppi.sif') 2. select the species of the network ('H.sapiens') 3. select the domain interaction dataset ('InterDom') 4. select initial network view ('extended')

small subnetwork of protein interactions by Rual et al.

Get additional information on proteins and domains

Hover the mouse over LCP2 protein node to get tooltip information on constituent domains and to highlight neighboring nodes

Right-click on LCP2 protein node: DomainGraph Options -> Detailed Information. Displays information on protein/constituent domains, GO and OMIM annotation

Right-click on LCP2 protein node: DomainGraph Options -> UniProt description. Links to the external webpage.

Graphical representation of protein domain architecture

Double-click on LCP2 protein node

Tooltip information for graphics

Hover the mouse over a domain box

Customizing/ exporting graphics

Right-click in the Data Panel (save as png, change domain colors)

Change network view

Plugins -> DomainGraph -> Change View. Select ppi network view.

The ppi network view can be used to explore the domain interactions in a stepwise manner

Stepwise exploration of protein and domain interaction network

Select protein nodes LCP2 and GRAP2: Get into the options dialog (Plugins -> DomainGraph -> Options). Choose to show domains for selected proteins.

Exon expression data integration

Plugins -> DomainGraph -> Integrate Affymetrix exon expression data

Import rma-sketch and dabg files for spleen and testis

Data obtained from Affymetrix, must be downloaded from their webpage! Data is stored in the local db.

Integrate testis expression data into sample network

select testis expression and pvalue data

Visualize domain/exon/probeset structures of proteins and present/absent probesets

double-click on LCP2 protein

Additional Information on domains/exons/probesets

hover the mouse over the boxes in the graphical representation

Compare similarities/dissimilarities in expression pattern across different tissues

create a new domain graph using the same sample network, this time integrate spleen tissue data.

DomainGraph -> Analysis -> intersection. Choose the two domain graphs for the analysis.

Nodes/edges with different biological types are highlighted.

Data / Session Files: sample_ppi.sif, DomainGraph_Session.cys (DomainGraph features like graphical representation cannot be saved!), Affymetrix data must be downloaded from Affymetrix directly.

Presentation: Attach your presentation

Webstart: Attach a webstart

Video: Attach a video link

DomainGraphRecipe (last edited 2009-02-12 01:03:01 by localhost)

Funding for Cytoscape is provided by a federal grant from the U.S. National Institute of General Medical Sciences (NIGMS) of the Na tional Institutes of Health (NIH) under award number GM070743-01. Corporate funding is provided through a contract from Unilever PLC.

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