Yuraszeck2010 - Vulnerabilities in the Tau Network in Tau Pathophysiology

  public model
Short description
Yuraszeck2010 - Vulnerabilities in the Tau Network in Tau Pathophysiology

This model is described in the article:

Yuraszeck TM, Neveu P, Rodriguez-Fernandez M, Robinson A, Kosik KS, Doyle FJ 3rd.
PLoS Comput. Biol. 2010; 6(11): e1000997

Abstract:

The multifactorial nature of disease motivates the use of systems-level analyses to understand their pathology. We used a systems biology approach to study tau aggregation, one of the hallmark features of Alzheimer's disease. A mathematical model was constructed to capture the current state of knowledge concerning tau's behavior and interactions in cells. The model was implemented in silico in the form of ordinary differential equations. The identifiability of the model was assessed and parameters were estimated to generate two cellular states: a population of solutions that corresponds to normal tau homeostasis and a population of solutions that displays aggregation-prone behavior. The model of normal tau homeostasis was robust to perturbations, and disturbances in multiple processes were required to achieve an aggregation-prone state. The aggregation-prone state was ultrasensitive to perturbations in diverse subsets of networks. Tau aggregation requires that multiple cellular parameters are set coordinately to a set of values that drive pathological assembly of tau. This model provides a foundation on which to build and increase our understanding of the series of events that lead to tau aggregation and may ultimately be used to identify critical intervention points that can direct the cell away from tau aggregation to aid in the treatment of tau-mediated (or related) aggregation diseases including Alzheimer's.

To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Format
SBML (L2V4)
Related Publication
  • Vulnerabilities in the tau network and the role of ultrasensitive points in tau pathophysiology.
  • Yuraszeck TM, Neveu P, Rodriguez-Fernandez M, Robinson A, Kosik KS, Doyle FJ 3rd
  • PLoS computational biology , 11/ 2010 , Volume 6 , pages: e1000997
  • Department of Chemical Engineering, University of California, Santa Barbara, Santa Barbara, California, USA.
  • The multifactorial nature of disease motivates the use of systems-level analyses to understand their pathology. We used a systems biology approach to study tau aggregation, one of the hallmark features of Alzheimer's disease. A mathematical model was constructed to capture the current state of knowledge concerning tau's behavior and interactions in cells. The model was implemented in silico in the form of ordinary differential equations. The identifiability of the model was assessed and parameters were estimated to generate two cellular states: a population of solutions that corresponds to normal tau homeostasis and a population of solutions that displays aggregation-prone behavior. The model of normal tau homeostasis was robust to perturbations, and disturbances in multiple processes were required to achieve an aggregation-prone state. The aggregation-prone state was ultrasensitive to perturbations in diverse subsets of networks. Tau aggregation requires that multiple cellular parameters are set coordinately to a set of values that drive pathological assembly of tau. This model provides a foundation on which to build and increase our understanding of the series of events that lead to tau aggregation and may ultimately be used to identify critical intervention points that can direct the cell away from tau aggregation to aid in the treatment of tau-mediated (or related) aggregation diseases including Alzheimer's.
Contributors
Audald Lloret i Villas, administrator

Metadata information

is
BioModels Database MODEL1408150000
BioModels Database BIOMD0000000542
isDescribedBy
PubMed 21085645
hasTaxon
Taxonomy Homo sapiens
isVersionOf
Gene Ontology inclusion body assembly
hasProperty
Human Disease Ontology Alzheimer's disease
Human Disease Ontology tauopathy
Curation status
Curated
Name Description Size Actions

Model files

BIOMD0000000542_url.xml SBML L2V4 representation of Yuraszeck2010 - Vulnerabilities in the Tau Network in Tau Pathophysiology 298.36 KB Preview | Download

Additional files

BIOMD0000000542.m Auto-generated Octave file 27.52 KB Preview | Download
BIOMD0000000542_urn.xml Auto-generated SBML file with URNs 296.58 KB Preview | Download
Yuraszeck2010.cps Copasi file of “Tau04MT” basal concentration 332.64 KB Preview | Download
5Yuraszeck2010.cps Copasi file of “Tau04MT” concentration when 5-fold increase in reaction 12 is implemented 330.58 KB Preview | Download
BIOMD0000000542.svg Auto-generated Reaction graph (SVG) 289.39 KB Preview | Download
BIOMD0000000542.sci Auto-generated Scilab file 154.00 bytes Preview | Download
BIOMD0000000542-biopax2.owl Auto-generated BioPAX (Level 2) 131.31 KB Preview | Download
BIOMD0000000542-biopax3.owl Auto-generated BioPAX (Level 3) 228.77 KB Preview | Download
BIOMD0000000542.xpp Auto-generated XPP file 21.04 KB Preview | Download
BIOMD0000000542.pdf Auto-generated PDF file 604.47 KB Preview | Download
BIOMD0000000542.vcml Auto-generated VCML file 900.00 bytes Preview | Download
BIOMD0000000542.png Auto-generated Reaction graph (PNG) 3.83 MB Preview | Download

  • Model originally submitted by : Audald Lloret i Villas
  • Submitted: Aug 15, 2014 10:58:21 AM
  • Last Modified: Dec 21, 2018 5:33:06 PM
Revisions
  • Version: 3 public model Download this version
    • Submitted on: Dec 21, 2018 5:33:06 PM
    • Submitted by: administrator
    • With comment: Include the additional files provided by the submitter in the original submission: Yuraszeck2010.cps, 5Yuraszeck2010.cps
  • Version: 2 public model Download this version
    • Submitted on: Sep 23, 2014 7:41:53 PM
    • Submitted by: Audald Lloret i Villas
    • With comment: Current version of Yuraszeck2010 - Vulnerabilities in the Tau Network in Tau Pathophysiology
  • Version: 1 public model Download this version
    • Submitted on: Aug 15, 2014 10:58:21 AM
    • Submitted by: Audald Lloret i Villas
    • With comment: Original import of Yuraszeck2010 - Vulnerabilities in the Tau Network in Tau Pathophysiology
Curator's comment:
(added: 15 Aug 2014, 12:18:53, updated: 15 Aug 2014, 12:18:53)
Aggregation-prone simulation from Figure 6 has been reproduced here. Percent change in microtubule bound 4R tau protein with respect to basal concentration during 5000 arbitrary units. Parameters are took from “Run1” of “Disease Params” sheet, on Dataset S1. To run this plot, the specie “Tau04MT” from Table S1 using the reactions from Table S2 is divided by the specie “Tau04MT” from Table S1 using the reactions from Table S2 including a 5-fold increase in the parameter associated with the binding of normally phosphorylated tau 3R to microtubules (reaction 12). The simulation was done using Copasi v4.12 (Build 81) and the plots were generated using Gnuplot. The models with simulation settings can be downloaded from the below links: - Copasi file of “Tau04MT” basal concentration - Copasi file of “Tau04MT” concentration when 5-fold increase in reaction 12 is implemented