The IBD interactome: an integrated view of aetiology, pathogenesis and therapy

IBD is a complex disease characterized by multiple interacting pathogenic components. In this Perspectives, the authors advocate studying the 'IBD interactome' to build a molecular network of IBD, and discuss new concepts and tools to implement an unbiased systems approach that could facil...

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Published inNature reviews. Gastroenterology & hepatology Vol. 14; no. 12; pp. 739 - 749
Main Authors de Souza, Heitor S. P., Fiocchi, Claudio, Iliopoulos, Dimitrios
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 01.12.2017
Nature Publishing Group
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Summary:IBD is a complex disease characterized by multiple interacting pathogenic components. In this Perspectives, the authors advocate studying the 'IBD interactome' to build a molecular network of IBD, and discuss new concepts and tools to implement an unbiased systems approach that could facilitate development of novel therapies. Crohn's disease and ulcerative colitis are prototypical complex diseases characterized by chronic and heterogeneous manifestations, induced by interacting environmental, genomic, microbial and immunological factors. These interactions result in an overwhelming complexity that cannot be tackled by studying the totality of each pathological component (an '–ome') in isolation without consideration of the interaction among all relevant –omes that yield an overall 'network effect'. The outcome of this effect is the 'IBD interactome', defined as a disease network in which dysregulation of individual –omes causes intestinal inflammation mediated by dysfunctional molecular modules. To define the IBD interactome, new concepts and tools are needed to implement a systems approach; an unbiased data-driven integration strategy that reveals key players of the system, pinpoints the central drivers of inflammation and enables development of targeted therapies. Powerful bioinformatics tools able to query and integrate multiple –omes are available, enabling the integration of genomic, epigenomic, transcriptomic, proteomic, metabolomic and microbiome information to build a comprehensive molecular map of IBD. This approach will enable identification of IBD molecular subtypes, correlations with clinical phenotypes and elucidation of the central hubs of the IBD interactome that will aid discovery of compounds that can specifically target the hubs that control the disease.
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ISSN:1759-5045
1759-5053
DOI:10.1038/nrgastro.2017.110