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DC-ATLAS: a systems biology resource to dissect receptor specific signal transduction in dendritic cells

Duccio Cavalieri1*, Damariz Rivero1, Luca Beltrame1, Sonja I Buschow2, Enrica Calura13, Lisa Rizzetto1, Sandra Gessani4, Maria C Gauzzi4, Walter Reith5, Andreas Baur6, Roberto Bonaiuti1, Marco Brandizi7, Carlotta De Filippo1, Ugo D'Oro8, Sorin Draghici9, Isabelle Dunand-Sauthier5, Evelina Gatti10, Francesca Granucci11, Michaela Gündel7, Matthijs Kramer12, Mirela Kuka8, Arpad Lanyi13, Cornelis JM Melief14, Nadine van Montfoort14, Renato Ostuni11, Philippe Pierre10, Razvan Popovici15, Eva Rajnavolgyi13, Stephan Schierer6, Gerold Schuler6, Vassili Soumelis16, Andrea Splendiani7, Irene Stefanini1, Maria G Torcia17, Ivan Zanoni11, Raphael Zollinger16, Carl G Figdor2 and Jonathan M Austyn18

Author Affiliations

1 Department of Pharmacology, University of Firenze, Firenze, Italy

2 Department of Tumor Immunology, NCMLS, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

3 Department of Biology, University of Padua, Padova, Italy

4 Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Roma, Italy

5 Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland

6 Department of Dermatology, University of Erlangen, Erlangen, Germany

7 Leaf Bioscience, Milano, Italy

8 Novartis Vaccines, Siena, Italy

9 Department of Computer Science, Wayne State University, Michigan, USA

10 Marseille-Luminy Immunology Center, Université de la Méditerranée, Marseille, France

11 Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milano, Italy

12 Department of Gastroenterology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

13 Institute of Immunology, University of Debrecen, Debrecen, Hungary

14 Department of Immunohematology and Bloodtransfusion, Leiden University Medical Center, Leiden, The Netherlands

15 Miravtech Corporation, Michigan, USA

16 Department of Immunology, Institute Curie, Paris, France

17 Department of Clinic Physiopathology, University of Firenze, Firenze, Italy

18 Nuffield Department of Surgery, University of Oxford, Oxford, UK

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Immunome Research 2010, 6:10  doi:10.1186/1745-7580-6-10

Published: 19 November 2010

Abstract

Background

The advent of Systems Biology has been accompanied by the blooming of pathway databases. Currently pathways are defined generically with respect to the organ or cell type where a reaction takes place. The cell type specificity of the reactions is the foundation of immunological research, and capturing this specificity is of paramount importance when using pathway-based analyses to decipher complex immunological datasets. Here, we present DC-ATLAS, a novel and versatile resource for the interpretation of high-throughput data generated perturbing the signaling network of dendritic cells (DCs).

Results

Pathways are annotated using a novel data model, the Biological Connection Markup Language (BCML), a SBGN-compliant data format developed to store the large amount of information collected. The application of DC-ATLAS to pathway-based analysis of the transcriptional program of DCs stimulated with agonists of the toll-like receptor family allows an integrated description of the flow of information from the cellular sensors to the functional outcome, capturing the temporal series of activation events by grouping sets of reactions that occur at different time points in well-defined functional modules.

Conclusions

The initiative significantly improves our understanding of DC biology and regulatory networks. Developing a systems biology approach for immune system holds the promise of translating knowledge on the immune system into more successful immunotherapy strategies.