A systems pharmacology model for inflammatory bowel disease.
Violeta Balbas-MartinezLeire Ruiz-CerdáItziar Irurzun-AranaIgnacio González-GarcíaAn VermeulenJosé David Gómez-MantillaIñaki F TrocónizPublished in: PloS one (2018)
In this article, we propose a logic model for Inflammatory Bowel Disease (IBD) which consists of 43 nodes and 298 qualitative interactions. The model presented is able to describe the pathogenic mechanisms of the disorder and qualitatively describes the characteristic chronic inflammation. A perturbation analysis performed on the IBD network indicates that the model is robust. Also, as described in clinical trials, a simulation of anti-TNFα, anti-IL2 and Granulocyte and Monocyte Apheresis showed a decrease in the Metalloproteinases node (MMPs), which means a decrease in tissue damage. In contrast, as clinical trials have demonstrated, a simulation of anti-IL17 and anti-IFNγ or IL10 overexpression therapy did not show any major change in MMPs expression, as corresponds to a failed therapy. The model proved to be a promising in silico tool for the evaluation of potential therapeutic targets, the identification of new IBD biomarkers, the integration of IBD polymorphisms to anticipate responders and non-responders and can be reduced and transformed in quantitative model/s.
Keyphrases
- clinical trial
- oxidative stress
- ulcerative colitis
- rheumatoid arthritis
- stem cells
- magnetic resonance imaging
- systematic review
- cell proliferation
- computed tomography
- squamous cell carcinoma
- endothelial cells
- randomized controlled trial
- mesenchymal stem cells
- radiation therapy
- mass spectrometry
- peripheral blood
- risk assessment