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Related Publication
  • Parameter adaptations during phenotype transitions in progressive diseases.
  • Tiemann CA, Vanlier J, Hilbers PA, van Riel NA
  • BMC systems biology , 10/ 2011 , Volume 5 , pages: 174
  • Department of BioMedical Engineering, Eindhoven University of Technology, Den Dolech 2, Eindhoven, 5612 AZ, The Netherlands. c.a.tiemann@tue.nl
  • The study of phenotype transitions is important to understand progressive diseases, e.g., diabetes mellitus, metabolic syndrome, and cardiovascular diseases. A challenge remains to explain phenotype transitions in terms of adaptations in molecular components and interactions in underlying biological systems.Here, mathematical modeling is used to describe the different phenotypes by integrating experimental data on metabolic pools and fluxes. Subsequently, trajectories of parameter adaptations are identified that are essential for the phenotypical changes. These changes in parameters reflect progressive adaptations at the transcriptome and proteome level, which occur at larger timescales. The approach was employed to study the metabolic processes underlying liver X receptor induced hepatic steatosis. Model analysis predicts which molecular processes adapt in time after pharmacological activation of the liver X receptor. Our results show that hepatic triglyceride fluxes are increased and triglycerides are especially stored in cytosolic fractions, rather than in endoplasmic reticulum fractions. Furthermore, the model reveals several possible scenarios for adaptations in cholesterol metabolism. According to the analysis, the additional quantification of one cholesterol flux is sufficient to exclude many of these hypotheses.We propose a generic computational approach to analyze biological systems evolving through various phenotypes and to predict which molecular processes are responsible for the transition. For the case of liver X receptor induced hepatic steatosis the novel approach yields information about the redistribution of fluxes and pools of triglycerides and cholesterols that was not directly apparent from the experimental data. Model analysis provides guidance which specific molecular processes to study in more detail to obtain further understanding of the underlying biological system.
Natal van Riel

Metadata information

BioModels Database MODEL1112150000
PubMed 22029623
Taxonomy Mus musculus
Mathematical Modelling Ontology Ordinary differential equation model
Human Disease Ontology fatty liver disease
Gene Ontology glucose homeostasis
Curation status
Name Description Size Actions

Model files

MODEL1112150000_url.xml SBML L2V4 representation of Tiemann2011_PhenotypeTransitions 36.77 KB Preview | Download

Additional files

MODEL1112150000.svg Auto-generated Reaction graph (SVG) 38.78 KB Preview | Download
MODEL1112150000-biopax2.owl Auto-generated BioPAX (Level 2) 18.61 KB Preview | Download
MODEL1112150000.sci Auto-generated Scilab file 5.20 KB Preview | Download
MODEL1112150000-biopax3.owl Auto-generated BioPAX (Level 3) 35.27 KB Preview | Download
MODEL1112150000.png Auto-generated Reaction graph (PNG) 101.58 KB Preview | Download
MODEL1112150000.pdf Auto-generated PDF file 2.80 KB Preview | Download
MODEL1112150000_urn.xml Auto-generated SBML file with URNs 41.08 KB Preview | Download
MODEL1112150000.m Auto-generated Octave file 7.09 KB Preview | Download
MODEL1112150000.vcml Auto-generated VCML file 576.00 bytes Preview | Download
MODEL1112150000.xpp Auto-generated XPP file 5.62 KB Preview | Download

  • Model originally submitted by : Natal van Riel
  • Submitted: Dec 15, 2011 7:57:03 PM
  • Last Modified: Aug 14, 2017 4:28:26 PM
  • Version: 3 public model Download this version
    • Submitted on: Aug 14, 2017 4:28:26 PM
    • Submitted by: Natal van Riel
    • With comment: Make updates on the model
  • Version: 2 public model Download this version
    • Submitted on: Aug 14, 2017 4:28:26 PM
    • Submitted by: Natal van Riel
    • With comment: Current version of Tiemann2011_PhenotypeTransitions
  • Version: 1 public model Download this version
    • Submitted on: Dec 15, 2011 7:57:03 PM
    • Submitted by: Natal van Riel
    • With comment: Original import of hepatic lipid and plasma lipoprotein metabolism