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 | 
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 | Right-click on LCP2 protein node: DomainGraph Options -> Detailed Information. Displays information on protein/constituent domains, GO and OMIM annotation | 
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 | Right-click on LCP2 protein node: DomainGraph Options -> UniProt description. Links to the external webpage. | 
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| Graphical representation of protein domain architecture | Double-click on LCP2 protein node | 
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| Tooltip information for graphics | Hover the mouse over a domain box | 
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| Customizing/ exporting graphics | Right-click in the Data Panel (save as png, change domain colors) | 
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| 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. | 
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| Exon expression data integration | Plugins -> DomainGraph -> Integrate Affymetrix exon expression data | 
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 | 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 | 
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| Visualize domain/exon/probeset structures of proteins and present/absent probesets | double-click on LCP2 protein | 
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| Additional Information on domains/exons/probesets | hover the mouse over the boxes in the graphical representation | 
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| 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. | 
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 | 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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