TranscriptomeBrowser and InteractomeBrowser

Category Cross-Omics>Pathway Analysis/Gene Regulatory Networks/Tools and Cross-Omics>Knowledge Bases/Databases/Tools

Abstract TranscriptomeBrowser (TBrowser) hosts a large database of transcriptional signatures (TS) extracted from the Gene Expression Omnibus (GEO) public microarray repository.

Transcriptional signatures (TS) have been produced using a new algorithm called “Density Based Filtering And Markov Clustering” (DBF-MCL).

The current database contains about 40,000 Transcriptional Signatures (TS) derived from ~ 4 000 microarray datasets (~222 million expression values).

Each TS was tested for functional enrichment using annotation obtained from numerous ontologies or annotation databases such as, Gene Ontology (GO), KEGG, BioCarta, Swiss-Prot, BBID, SMART, NIH Genetic Association DB, COG/KOG, TargetScan, PicTar, TFBS_conserv.ed., MSigDB, GeneSigDB, etc.

TBrowser comes with a sophisticated search engine so that users can search for the biological contexts in which several genes were concomitantly regulated and combined queries using Boolean operators.

InteractomeBrowser --

The InteractomeBrowser plugin is an advanced tool that lets you get quick access to a knowledge database that includes both predicted and validated molecular interactions.

InteractomeBrowser is available through the TranscriptomeBrowser framework.

To create the InteractomeBrowser portion of the database, the manufacturers extended the previously developed TranscriptomeBrowser database with a set of tables containing ~ 1,594,978 human and mouse molecular interactions.

The database includes:

1) Predicted regulatory interactions (computed by scanning vertebrate alignments with a set of 1,213 position weight matrices);

2) Potential regulatory interactions inferred from systematic analysis of ChIP-seq experiments;

3) Regulatory interactions curated from the literature;

4) Predicted post-transcriptional regulation by micro-RNA;

5) Protein kinase-substrate interactions; and

6) Physical protein-protein interactions.

In order to easily retrieve and efficiently analyze these interactions, the manufacturers developed InteractomeBrowser, a graph-based knowledge browser that comes as a plug-in for TranscriptomeBrowser (as stated above...).

The first objective of InteractomeBrowser is to provide a user-friendly tool to get new insight into any gene list, by providing a context-specific display of putative regulatory and physical interactions.

To achieve this, InteractomeBrowser relies on a “cell compartments-based layout” that makes use of a subset of the Gene Ontology (GO) to map gene products onto relevant cell compartments.

This layout is particularly advanced for visual integration of heterogeneous biological information and is a productive avenue in generating new hypotheses.

The second objective of InteractomeBrowser is to fill the gap between interaction databases and dynamic modeling.

It is thus compatible with the network analysis software tool Cytoscape and with the Gene Interaction Network simulation software (GINsim).

InteractomeBrowser’s main use is to display networks, given an input list of genes (as stated above...).

The interactions represented in these networks are mined from several databases (see list below...) and are of different natures (proteins belonging to the same complex, kinase-substrate relations, transcriptional regulations, etc.).

Currently, InteractomeBrowser integrates the following interaction databases:

Physical interactions:

1) HPRD (v. 9 - 04/13/2010);

2) Intact (11/15/2010); and

3) KEA (2009).

Regulatory interactions:

1) CHEA (10/06/2010);

2) LymphTF-DB (12/02/2009);

3) OREGANNO (11/2009);

4) TFBSConserved (based on hg18 - 07/2007);

5) TranscriptomeBrowser motif conservation (TBMC, 05/2011); and

6) TargetScan (06/2011)

InteractomeBrowser features an original “cell compartments-based layout”. It provides a hierarchical representation of cellular compartments, and genes of the network are placed in their respective compartments (as stated above...).

More precisely, the manufacturer's defined an Ontology describing cell compartments (with some accurate terms, and some more general terms), which is a subset of GeneOntology:Cell Compartment.

The layout is a direct representation of this ontology: small compartments included in bigger compartments correspond to accurate terms that have an “is_a” relationship with another more general term.

InteractomeBrowser Display options -- The “nodes placement” is controlled by a force-based layout: the nodes are repulsive to each other, they are attracted to their respective compartments, and edges act like springs.

The force-based layout can be switched off or on at any moment through the Display menu. Some parameters of the force-based layout (edge length and edge torsion) can be modified in the same menu.

The network area can be maximized by pressing Alt+F, or by selecting “Full window” in the Display menu. In order to “clean” the network from orphan nodes and empty compartments, you can select the “Hide orphan nodes” option.

An option called “Hide intercompartmental edges” allows you to remove several unlikely edges of the network, when they involve genes belonging to distant compartments.

Interacting with the network -- You can select a gene by clicking on its name (in the list), or clicking on its representing node in the network display.

The Edit menu provides several options for selection and removal of genes. When your mouse is over a node or an edge, you can read information about it, via the “Infos” tab.

Right-clicking on a node will open a context menu, allowing you to:

1) Open the NCBI web page for this gene;

2) Add regulatory interactions involving this gene and other genes of the network; and

3) Move the node to another compartment.

The action menu provides other tools to expand the network:

1) Add all the interactors of the selected genes; and

2) Add common interactors of the selected genes; etc.

InteractomeBrowser also provides an on-the-fly enrichment analysis tool.

Select several nodes and click on the “Biological process enrichment analysis” option, and it will pop up a window(s) with the results of this analysis.

InteractomeBrowser Export options -- Networks created with InteractomeBrowser can be exported in various formats:

1) Images (jpg, bmp, gif, png);

2) XML format suitable for Cytoscape; and

3) GINML format, to import it into GINsim.

System Requirements

Contact manufacturer.

Manufacturer

Manufacturer Web Site TranscriptomeBrowser and InteractomeBrowser

Price Contact manufacturer.

G6G Abstract Number 20711

G6G Manufacturer Number 104288