DC-ATLAS databaseDatabases, factual
We have been developing the DC-ATLAS DC-pathway database. For this, we have set about identifying key signalling pathways that were likely to be of most relevance to dendritic cell functions. We have designed a DC-ATLAS data model to effectively describe pathways, their genes, and their interaction. We produced a controlled vocabulary that contains at least 400 ontological terms, prepared on the basis of the proposals and discussions among the researchers involved in DC-ATLAS project. We defined the pathway representation where each pathway was described using three different means: a PDF format, a gene list, and a graphical representation. The pathways data model and controlled vocabulary was developed in collaboration with Sorin Draghici and the Leaf Bioscience group lead by A. Splendiani.
DC ATLAS integrates the signalling modules of the DC, curating specifically
(i) the pathways leading from immature dendritic cells to mature dendritic cells, and
(ii) the pathways depending on interaction between different cell types (e.g. DC and T cells interaction, leading to Th1/Th2/Th17/Treg polarisation, and apoptosis).
Given the complexity of the problem we have built a unique group of curators with the primary purpose of describing separately:
(1) the section of the pathway sensing the stimulus and transmitting the stimulus to the general signal transduction pathway;
(2) the principal signal transduction modules used by the DC; and
(3) the outcomes (e.g. cytokine production, apoptosis, migration, differentiation).
From over 200 pathways, a list of some 30-40 was prioritised for immediate attention. These were then assigned to individual curators, drawn from across the Network and including some of its Third Parties. Among the curated pathways are TCR/ slam receptor; PPAR P PPAR Gamma; TCR Ag proc/pres; TLR4; TLR7+8; TLR 2 + 1; TLR6+2; MHC1 MHC2 pathways- antigen presentation; TLR3; DC-Sign; TLR 5+; TCR – motility; Dectin-1.
The curation process revealed substantial inaccuracies and errors in publicly-available databases. For the first time, this initiative clarified differences between homologous pathways operating in dendritic cells from human versus mouse (and other species), and in dendritic cells from different sources (e.g. human monocytes-derived versus mouse bone marrow-derived DC, and different primary DC subsets). Draft manuscripts, describing this initiative and its first results were prepared and will be submitted as DC-THERA joint publications.
DC-ATLAS Curation Team:
- Francesca Granucci / Ivan Zanoni, Università di Milano-Bicocca
- Ugo D’Oro / Mirela Kuka, Novartis
- Sonja Buschow, University of Nijmegen
- Sandra Gessani / Maria Cristina Gauzzi, ISS
- Philippe Pierre, Centre d’Immunologie de Marseille-LuminyCNRS-INSERM-Univ. Med.
- Nadine Montfoort, LUMC
- Vassili Soumelis, Curie Institute
- Arpad Lanyi, University of Debrecen
- Eva Rajnavolgyi, University of Debrecen
- Walter Reith, Isabelle Dunand, University of Geneva
- Sebastian Amigorena, Curie Institute
- Herman Wagner, TUM
- Carl Figdor, University of Nijmegen
- Gabriella Torcia, University of Florence
- Matthijs Kramer, Radboud University Nijmegen Medical Centre