Anaphylaxis is a life-threatening, generalized systemic allergic reaction, which often occurs within minutes following the exposure of antigens, such as food, drugs, insect stings and others. Classically, anaphylaxis is thought to be mainly caused by an IgE-mediated sudden activation of mast cells and basophils. Recent evidence added another layer of complexity into the pathogenesis of anaphylaxis by showing the fact that it might be also triggered by several IgE-independent mechanisms. Even in Australia and USA alone, anaphylaxis incidence has been increased over the last decades, incurring a very high eco-social burden. Therefore, it is extremely important to delineate the inter- and intra-cellular molecular networks and the various antigen-specific mechanisms following the exposure of different antigens underlying this life-threatening condition. This shall further facilitate anaphylaxis disease management that is extremely challenging due to the extremely narrow window between an unexpected antigen exposure and its rapid progression. An essential approach to leverage the holistic understanding of the underlying mechanisms and facilitate the future clinical decision making is to computationally reconstruct and manually curate a disease-specific network for anaphylaxis.
In this project, we review different pathways, interaction and clinical-knowledge databases in order to identify pathways and interactions relevant to anaphylaxis mechanisms. Then, we translate these pathways and interactions into a molecular interaction map followed by manual curation of clinical experts. Following the map construction, we intend to implement differential network analysis among anaphylaxis patients to further stratify patient subgroups using available multi-layer 'omics data. The success of this project will result in the prototype of the first comprehensive machine-readable and clinical-expert-friendly anaphylaxis disease map.
The anaphylaxis map is being developed by employing the frameworks of the AsthmaMap and the Parkinson’s disease map.
Feng He, PhD Luxembourg Institute of Health, Luxembourg Head of Immune Systems Biology Group, Department of Infection and Immunity |
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Ling Xiao, MS Luxembourg Institute of Health, Luxembourg Intern, Department of Infection and Immunity |
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Marek Ostaszewski, PhD University of Luxembourg, Luxembourg Researcher, Luxembourg Centre for Systems Biomedicine |
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Reinhard Schneider, PhD University of Luxembourg, Luxembourg Head of Bioinformatics Core, Luxembourg Centre for Systems Biomedicine |
Markus Ollert, MD Luxembourg Institute of Health, Luxembourg Professor of Molecular Dermatology and Immunology Director, Department of Infection and Immunity |
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Carsten Bindslev-Jensen, MD Odense Research Centre for Anaphylaxis, Odense, Denmark Head of Department, Chief Physician |
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Sebastian Bode, MD Luxembourg Institute of Health, Luxembourg Pediatrician, Clinician Scientist, Department of Infection and Immunity |