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A systems pharmacology model for inflammatory bowel disease

(2018) PLOS ONE. 13(3).
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Abstract
Motivation : The literature on complex diseases is abundant but not always quantitative. This is particularly so for Inflammatory Bowel Disease (IBD), where many molecular pathways are qualitatively well described but this information cannot be used in traditional quantitative mathematical models employed in drug development. We propose the elaboration and validation of a logic network for IBD able to capture the information available in the literature that will facilitate the identification/validation of therapeutic targets. Results : 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-TNF alpha, 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-IFN gamma 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.
Keywords
ANTIINTERFERON-GAMMA ANTIBODY, CROHNS-DISEASE, SIGNAL-TRANSDUCTION, ULCERATIVE-COLITIS, MONOCYTE APHERESIS, MONOCLONAL-ANTIBODY, NATURAL-HISTORY, CLINICAL-COURSE, DOUBLE-BLIND, EFFICACY

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Citation

Please use this url to cite or link to this publication:

MLA
Balbas-Martinez, Violeta et al. “A Systems Pharmacology Model for Inflammatory Bowel Disease.” PLOS ONE 13.3 (2018): n. pag. Print.
APA
Balbas-Martinez, V., Ruiz-Cerda, L., Irurzun-Arana, I., Gonzalez-Garcia, I., Vermeulen, A., Gomez-Mantilla, J. D., & Troconiz, I. F. (2018). A systems pharmacology model for inflammatory bowel disease. PLOS ONE, 13(3).
Chicago author-date
Balbas-Martinez, Violeta, Leire Ruiz-Cerda, Itziar Irurzun-Arana, Ignacio Gonzalez-Garcia, An Vermeulen, Jose David Gomez-Mantilla, and Inaki F Troconiz. 2018. “A Systems Pharmacology Model for Inflammatory Bowel Disease.” Plos One 13 (3).
Chicago author-date (all authors)
Balbas-Martinez, Violeta, Leire Ruiz-Cerda, Itziar Irurzun-Arana, Ignacio Gonzalez-Garcia, An Vermeulen, Jose David Gomez-Mantilla, and Inaki F Troconiz. 2018. “A Systems Pharmacology Model for Inflammatory Bowel Disease.” Plos One 13 (3).
Vancouver
1.
Balbas-Martinez V, Ruiz-Cerda L, Irurzun-Arana I, Gonzalez-Garcia I, Vermeulen A, Gomez-Mantilla JD, et al. A systems pharmacology model for inflammatory bowel disease. PLOS ONE. 2018;13(3).
IEEE
[1]
V. Balbas-Martinez et al., “A systems pharmacology model for inflammatory bowel disease,” PLOS ONE, vol. 13, no. 3, 2018.
@article{8611952,
  abstract     = {Motivation : The literature on complex diseases is abundant but not always quantitative. This is particularly so for Inflammatory Bowel Disease (IBD), where many molecular pathways are qualitatively well described but this information cannot be used in traditional quantitative mathematical models employed in drug development. We propose the elaboration and validation of a logic network for IBD able to capture the information available in the literature that will facilitate the identification/validation of therapeutic targets. 
Results : 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-TNF alpha, 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-IFN gamma 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.},
  articleno    = {e0192949},
  author       = {Balbas-Martinez, Violeta and Ruiz-Cerda, Leire and Irurzun-Arana, Itziar and Gonzalez-Garcia, Ignacio and Vermeulen, An and Gomez-Mantilla, Jose David and Troconiz, Inaki F},
  issn         = {1932-6203},
  journal      = {PLOS ONE},
  keywords     = {ANTIINTERFERON-GAMMA ANTIBODY,CROHNS-DISEASE,SIGNAL-TRANSDUCTION,ULCERATIVE-COLITIS,MONOCYTE APHERESIS,MONOCLONAL-ANTIBODY,NATURAL-HISTORY,CLINICAL-COURSE,DOUBLE-BLIND,EFFICACY},
  language     = {eng},
  number       = {3},
  pages        = {19},
  title        = {A systems pharmacology model for inflammatory bowel disease},
  url          = {http://dx.doi.org/10.1371/journal.pone.0192949},
  volume       = {13},
  year         = {2018},
}

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