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.

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