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Singular manifolds of proteomic drivers to model the evolution of inflammatory bowel disease status
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 c...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643119/ https://www.ncbi.nlm.nih.gov/pubmed/33149233 http://dx.doi.org/10.1038/s41598-020-76011-7 |
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author | Morilla, Ian Léger, Thibaut Marah, Assiya Pic, Isabelle Zaag, Hatem Ogier-Denis, Eric |
author_facet | Morilla, Ian Léger, Thibaut Marah, Assiya Pic, Isabelle Zaag, Hatem Ogier-Denis, Eric |
author_sort | Morilla, Ian |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7643119 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-76431192020-11-06 Singular manifolds of proteomic drivers to model the evolution of inflammatory bowel disease status Morilla, Ian Léger, Thibaut Marah, Assiya Pic, Isabelle Zaag, Hatem Ogier-Denis, Eric Sci Rep Article 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. Nature Publishing Group UK 2020-11-04 /pmc/articles/PMC7643119/ /pubmed/33149233 http://dx.doi.org/10.1038/s41598-020-76011-7 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Morilla, Ian Léger, Thibaut Marah, Assiya Pic, Isabelle Zaag, Hatem Ogier-Denis, Eric Singular manifolds of proteomic drivers to model the evolution of inflammatory bowel disease status |
title | Singular manifolds of proteomic drivers to model the evolution of inflammatory bowel disease status |
title_full | Singular manifolds of proteomic drivers to model the evolution of inflammatory bowel disease status |
title_fullStr | Singular manifolds of proteomic drivers to model the evolution of inflammatory bowel disease status |
title_full_unstemmed | Singular manifolds of proteomic drivers to model the evolution of inflammatory bowel disease status |
title_short | Singular manifolds of proteomic drivers to model the evolution of inflammatory bowel disease status |
title_sort | singular manifolds of proteomic drivers to model the evolution of inflammatory bowel disease status |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643119/ https://www.ncbi.nlm.nih.gov/pubmed/33149233 http://dx.doi.org/10.1038/s41598-020-76011-7 |
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