geWorkbench

Outline

This tutorial contains

1. . an overview of the Cellular Networks KnowledgeBase and
2. . instructions....

(This tutorial is under construction 5/18/2007)

Overview

The Cellular Network Knowledge Base (CNKB) is a repository of interactions between pairs of proteins (these interactions can be either computationally or experimentally derived). Both direct, physical interactions can be captured as well as indirect transcriptional relationships (where an interaction is between a transcription factor and its gene target). Each pairwise interaction has an associated confidence indicator (a value between 0 and 1) reflecting the strength of the underlying data, whether experimental or computational.

This component allows the user to select a group of markers and specify for each the interaction type of interest (Protein-Protein and/or Protein-DNA). All interactions (of the designated types) involving the selected markers are retrieved from the CNKB and displayed (along with associated information such as GO annotation, interaction attributes, etc) both in the CNKB component and also in Cytoscape.

GUI

The CNKB component displays a list of markers that have been activated in the Markers component. The user can select from these markers by double-clicking them; those selected will be added to the Selected Marker List just below.

Activated Marker List

This table contains three columns: Marker, Gene (the gene name corresponding to the marker, if available), and Gene Type. The possible values in the Gene Type column are

1. TF - Transcription Factor,
2. K - Kinase,
3. P - Phosphatase, and
4. (no entry) - type is unknown.

These gene types are derived from the GO annotation associated with a gene name.

Selected Marker List

The Selected Markers List table contains activated markers moved over from the Activated Markers table. In addition to the columns defined for the Activated Marker List, the Selected Marker List adds the following:

1. Entrez Id: The Entrez ID of the gene name. When present, the Entrez ID is hyperlinked to the relevant entry within Entrez Gene .
2. GO Term: Associated GO Term. Users can browse the GO terms associated with a gene (using an AmiGO browser-like interface) and select one of those terms for display.
3. Prot-Prot #: number of protein-protein interactions (reported in the CNKB) involving the gene.
4. Prot-DNA #: number of protein-DNA interactions (reported in the CNKB) involving the gene.

Additionally, each row has check-boxes that can be used to designate whether protein-protein, protein-DNA, or both types of interactions should be used.

Items that have been added to the Selected Markers list are initially shown in red, using an italic font, to indicate the CKNB has not yet been queried to retrieve their interaction information. After the query has been completed they are displayed in a black, normal font.

Items that have been added to the Selected Markers list can be removed and sent back to the Activated Markers list by double clicking on their entries.

Preferences

Using a “preferences”-type tab, the user can control how many of the columns listed above are visible within the Selected Markers table.

Throttle Graph

This interactive graph allows users to "throttle" (for the genes in the Selected Markers table) which interactions to work with, using as a criterion the interactions’ confidence indicator. As the required threshold of likelihood of the interactions is increased, the sum of interactions meeting this criterion decreases.

Cytoscape Viewer

The network created using the selected interactions can be displayed in the Cytoscape component.

Create Network

Once the desired set of markers is present and its interation data has been retrieved from the database, an adjacency matrix can be computed by clicking the "Create Network" button. The resulting matrix is placed in the Project Folders component under its parent microarray dataset.

Example

1. Select markers in Markers component to add to a marker set.
2. Activate the set. Its members will now appear in the Activate Marker List in the CNKB component.
3. Select markers to move to the Select Marker List by double clicking.
4. (Markers in the Selected Marker List can be removed by double-clicking on them, sending them back to the Activated Marker list).
5. Mark the check-boxes for the type of interactions desired.
6. Hit the refresh button to query the database for interacton information for these markers.
7. Adjust the throttle graph if desired to limit the interactions to be used in building an adjacency matrix based on the assigned confidence values.
8. Hit the Create Network button.
9. View the result in Cytoscape.

Data Sources

Cellular Network Knowledge Base (CNKB) Source Descriptions & Interaction Statistics

B-cell lymphoma Interactome (Della Favera/ Califano labs, collected by Celine Lefebvre)

• 12,902 protein-dna interactions
• 22,734 protein-protein interactions

Munich Information Center for Protein Sequences

• http://mips.gsf.de/proj/ppi/
• 322 protein-protein interactions

Protein-protein interaction database at EBI. No species restriction.

• http://www.ebi.ac.uk/intact/site/index.jsf
• 7,701 interactions

The Molecular INTeraction database

• http://mint.bio.uniroma2.it/mint/Welcome.do
• 3,196 human interactions
• MINT focuses on experimentally verified protein interactions mined from the scientific literature by expert curators.

The Biomolecular Interaction Network Database

• http://bond.unleashedinformatics.com/Action?pg=23299#BIND
• 48,573 protein-protein interactions (various species)

Database of Interacting Proteins

• http://dip.doe-mbi.ucla.edu/dip/Guide.cgi
• 820 human protein-protein interaction pairs

Reactome knowledgebase

• http://www.reactome.org/
• Reactome knowledgebase
• 27,534 human protein-protein interaction pairs

Human Protein Reference Database

• http://www.hprd.org/
• 36,501 protein-protein interactions

Geneways

• http://geneways.genomecenter.columbia.edu/
• 27,938 interactions
• GeneWays is a system for automatically extracting, analzying, visualizing and integrating molecular pathway data from the research literature.