Author:
Morilla Ian,Léger Thibaut,Marah Assiya,Pic Isabelle,Zaag Hatem,Ogier-Denis Eric
Abstract
Abstract
The conditions used to describe the presence of an immune disease are often represented by interaction graphs. These informative, but intricate structures are susceptible to perturbations at different levels. The mode in which that perturbation occurs is still of utmost importance in areas such as cell reprogramming and therapeutics models. In this sense, module identification can be useful to well characterise the global graph architecture. To help us with this identification, we perform topological overlap-related measures. Thanks to these measures, the location of highly disease-specific module regulators is possible. Such regulators can perturb other nodes, potentially causing the entire system to change behaviour or collapse. We provide a geometric framework explaining such situations in the context of inflammatory bowel diseases (IBD). IBD are severe chronic disorders of the gastrointestinal tract whose incidence is dramatically increasing worldwide. Our approach models different IBD status as Riemannian manifolds defined by the graph Laplacian of two high throughput proteome screenings. It also identifies module regulators as singularities within the manifolds (the so-called singular manifolds). Furthermore, it reinterprets the characteristic nonlinear dynamics of IBD as compensatory responses to perturbations on those singularities. Then, particular reconfigurations of the immune system could make the disease status move towards an innocuous target state.
Funder
Agence Nationale de la Recherche
Publisher
Springer Science and Business Media LLC
Reference32 articles.
1. Dahlhamer, J. M., Zammitti, E. P., Ward, B. W., Wheaton, A. G. & Croft, J. B. Prevalence of inflammatory bowel disease among adults aged $$\ge$$18 years-United States, 2015. MMWR Morb. Mortal. Wkly. Rep. 65(42), 1166–1169 (2016).
2. Farraye, F. A., Melmed, G. Y., Lichtenstein, G. R. & Kane, S. V. ACG clinical guideline: Preventive care in inflammatory bowel disease. Am. J. Gastroenterol. 112(2), 241–258.
https://doi.org/10.1038/ajg.2016.537
(2017).
3. Burisch, J., Jess, T., Martinato, M. & Lakatos, P. L. The burden of inflammatory bowel disease in Europe. J. Crohn. Colit. 7, 322–337 (2013).
4. King, D. et al. Incidence and prevalence of inflammatory bowel disease in the UK between 2000 and 2016 and associated mortality and subsequent risk of colorectal cancer. United Eur. Gastroenterol.
https://doi.org/10.1038/ajg.2016.537
(2019).
5. Belkin, M., Que, Q., Wang, Y. & Zhou, X. Toward understanding complex spaces: Graph laplacians on manifolds with singularities and boundaries. In MLR: Workshop and Conference Proceedings; 25th Annual Conference on Learning Theory, vol 36, 1–24 (2012).
Cited by
2 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献