DC-ATLAS

Category Cross-Omics>Pathway Analysis/Gene Regulatory Networks/Tools

Abstract DC-ATLAS is a systems biology approach to signal transduction pathways in dendritic cells (DCs).

The major scientific and technological goal of DC-ATLAS is to generate complete maps of the intracellular signaling pathways and regulatory networks that govern DC maturation/activation and function.

DC-ATLAS is composed of DC-PATH, an extensively curated signal transduction pathway database, and DC-BASE, a repository for DC microarray experiments.

The crosstalk between these databases allows the analysis of high throughput data in a DC-specific manner using a set of highly standardized and reproducible procedures.

Enabling a systems biology approach to DC biology holds the promise for spinning molecular immunology into more successful immunotherapy strategies.

DC-ATLAS motivation/features --

Studying DCs using an immune systems biology approach facilitated by DC-ATLAS, holds promise to dissect the integrated signals from these cells.

This allows one to build models of the complex process of DC regulation and generate predictions and hypotheses about DC function under physiological and pathological conditions.

However, the road forward is Not without obstacles. There is a strong need of a greater coverage of network data, improved accuracy and standardization of annotation.

The extraction of signal transduction maps from gene expression data requires well-structured pathway definitions.

Similarly to the recently published DC pathway map, DC ATLAS is an integrated project incorporating both immunology and bioinformatics, focused on signaling pathways in DCs (as stated above...).

Yet, with respect to other existing resources, DC-ATLAS denotes major advancements. It describes the reactions based on consensus reached by a large number of leading European immunological scientists with expertise in DCs.

The pathways represent a valuable tool to emphasize established facts as well as to highlight limitations in ones knowledge with respect to the hierarchy of events leading to effective immune responses.

DC-ATLAS is one of the first SBGN compliant pathway databases implemented using the Biological Connection Markup Language (BCML).

DC-ATLAS integrates detailed pathway information with experimental data allowing data analysis in a DC-specific manner. It is one of the first examples of a modular approach to describe signal transduction pathways.

In DC-ATLAS, sets of reactions that participate in a common regulatory unit were functionally categorized as part of what the manufacturer’s defined as a “module”.

The interconnected modules, which describe the DC-ATLAS pathways from receptors to effectors via signal mediators, overcome a major limitation of the current pathway structures, in which specific events are masked by a plethora of generic interactions.

DC-PATH - DC-Atlas Signaling Pathways repository --

DC-ATLAS aims at generating a complete and integrated description of the intracellular signaling pathways operating in DCs.

Seventeen (17) pathways (see below...) have been curated so far (as of January 2011), on the basis of information available in existing databases and literature, as well as experimental evidence generated in the laboratories of the researchers involved in the DC-ATLAS project.

Pathways have been curated by carefully annotating the species in which relevant data have been generated and exclusively describe interactions proven in DCs.

DC-PATH contains an initial panel of pathways critical for DC maturation, migration, antigen presentation and interactions with other immune cells.

Curators described each pathway by creating a gene list, a graphical representation and a text file containing a controlled vocabulary compliant detailed description of the pathway itself.

To view correctly the various files associated to a pathway, you will need additional software:

1) A Portable Document Format (PDF) viewer.

2) GenMAPP Pathway Markup Language (GPML) format: PathVisio - PathVisio is a tool for displaying and editing biological pathways in the GPML format.

3) INOH format: INOH Client - The INOH Client is the client software for retrieving diagram data from a signaling pathway database system and editing them.

4) Excel files: An Excel compatible spreadsheet program.

Controlled Vocabularies of the Dendritic Cell --

Controlled vocabularies have been built to clearly annotate the components of the pathways, their interactions and their location.

These vocabularies have been created using the Open Biomedical Ontologies, integrated with DC-specific terms.

This process reduced the complexity of molecular interactions, such as complex formation, nuclear translocation and post-translational modifications to a widely accepted representation.

DC-ATLAS Pathway list (as of January 2011) --

TLR1-2 Signaling Pathway; TLR3 Signaling Pathway; TLR4 Signaling Pathway;

TLR5 Signaling Pathway; TLR2-6 Signaling Pathway; TLR7 Signaling Pathway;

TLR8 Signaling Pathway; TLR9 Signaling Pathway; DC-SIGN Signaling Pathway;

DECTIN-1 Signaling Pathway; Fc-gamma Receptor Signaling Pathway; MDA5 Signaling Pathway;

PPAR-gamma Signaling Pathway; Regulation of actin cytoskeleton and Phagosome Involvement Pathway;

SLAM Receptor-CD84 Signaling Pathway; MHCI Pathway; and MHCII Pathway.

DC-ATLAS additional info --

For additional info on DC-ATLAS please see the following paper:

D Cavalieri, D Rivero, L Beltrame, et al; DC-ATLAS: a systems biology resource to dissect receptor specific signal transduction in dendritic cells; Immunome Research 2010, 6:10.

System Requirements

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Manufacturer

Manufacturer Web Site DC-ATLAS

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G6G Abstract Number 20741

G6G Manufacturer Number 104327