Network analysis of inflammatory bowel disease research: Towards the interactome

Abstract

Modern views accept that Inflammatory Bowel Diseases (IBD) emerge from complex interactions among the multiple components of a biological network known as "IBD interactome". These diverse components belong to different functional levels including cells, molecules, genes and biological processes. This diversity can make it difficult to integrate available empirical information in human patients into a collective view of etiopathogenesis, a necessary step to understand the interactome. Herein, we quantitatively analyze how representativeness of components involved in human IBD and their relations have changed over time.Methods: A bibliographic search in PubMed retrieved 25971 abstracts of experimental studies on IBD in humans, published between 1990 and 2020. Abstracts were scanned automatically for 1218 IBD interactome components proposed in recent reviews. The resulting databases are freely available and were visualized as networks indicating the frequency in which different components are referenced together within each abstract. As expected, over time there was an increase in components added to the IBD network and heightened connectivity within and across functional levels. However, certain components were consistently studied together forming preserved motifs in the networks. These overrepresented and highly linked components reflect main "hypotheses" in IBD research in humans. Interestingly, 82% of the components cited in reviews were absent or showed low frequency, suggesting that many aspects of the proposed IBD interactome still possess weak experimental support in humans.