Network Analysis of Inflammatory Bowel Disease Research: Towards the Interactome.

Background And Aims: Modern views accept that inflammatory bowel diseases [IBD] emerge from complex interactions among the multiple components of a biological network known as the '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 from human patients into a collective view of aetiopathogenesis, a necessary step to understand the interactome. Herein, we quantitatively analyse how the representativeness of components involved in human IBD and their relationships ha ve changed over time.

Methods: A bibliographic search in PubMed retrieved 25 971 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 at which different components are referenced together within each abstract.

Results: 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 have weak experimental support in humans.

Conclusions: A reductionist and fragmented approach to the study of IBD has prevailed in previous decades, highlighting the importance of transitioning towards a more integrated interactome framework.