Dunster2016 - Nondimensional Coagulation Model

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Model Identifier
BIOMD0000000925
Short description
We undertake a mathematical investigation of a model for the generation of thrombin, an enzyme central to haemostatic blood coagulation, as well as to thrombotic disorders, that is the end product of a complicated protein cascade with multiple feedbacks that ensures its production in the right place at the right time. In a laboratory setting, its central role is reflected in thrombin evolution over time being used as a measure of the ability of a patient's blood to clot. Here, we present a model for the generation of thrombin (based on earlier work) and analyse it using the method of matched asymptotic expansions to derive a sequence of simplified models that characterize the roles of distinct interactions over various timescales. In particular, we are able through the asymptotic analysis to provide simplified models that are an excellent substitute for the full model (capturing the explosive growth and decay of thrombin) and approximations for the key experimental measurements used to describe thrombin's characteristic evolution over time. The asymptotic results are validated against numerical simulations.
Format
SBML (L2V4)
Related Publication
  • Mathematical modelling of thrombin generation: asymptotic analysis and pathway characterization
  • J. L. Dunster, J. R. King
  • IMA Journal of Applied Mathematics , 2/ 2017 , Volume 82 , Issue 1 , pages: 60-96 , DOI: 10.1093/imamat/hxw007
  • Department of Mathematics and Statistics, Institute for Cardiovascular and Metabolic Research, School of Biological Sciences, University of Reading, Reading, UK.
  • We undertake a mathematical investigation of a model for the generation of thrombin, an enzyme central to haemostatic blood coagulation, as well as to thrombotic disorders, that is the end product of a complicated protein cascade with multiple feedbacks that ensures its production in the right place at the right time. In a laboratory setting, its central role is reflected in thrombin evolution over time being used as a measure of the ability of a patient's blood to clot. Here, we present a model for the generation of thrombin (based on earlier work) and analyse it using the method of matched asymptotic expansions to derive a sequence of simplified models that characterize the roles of distinct interactions over various timescales. In particular, we are able through the asymptotic analysis to provide simplified models that are an excellent substitute for the full model (capturing the explosive growth and decay of thrombin) and approximations for the key experimental measurements used to describe thrombin's characteristic evolution over time. The asymptotic results are validated against numerical simulations.
Contributors
Matthew Roberts, Ahmad Zyoud

Metadata information

hasTaxon
Taxonomy Homo sapiens
isVersionOf
Gene Ontology blood coagulation
hasProperty
Mathematical Modelling Ontology Ordinary differential equation model
occursIn
Brenda Tissue Ontology blood
isDescribedBy

Curation status
Curated


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Model files

Dunster2016_Nondimensional_Model_Curated.xml SBML L2V4 representation of Dunster2016 - Nondimensional Coagulation Model_Curated-Figure 4 178.02 KB Preview | Download

Additional files

Dunster2016_Nondimensional_Model_Curated.cps COPASI version 4.27 (Build 217) representation of Dunster2016 - Nondimensional Coagulation Model_Curated-Figure 4 295.14 KB Preview | Download
Dunster2016_Nondimensional_Model1.sedml sed-ml L1V2 representation of Dunster2016 - Nondimensional Coagulation Model_Curated-Figure 4 14.96 KB Preview | Download
Dunster2016_Nondimensional_Model (1).xml SBML L2V4 representation of Dunster2016 - Nondimensional Coagulation Model_Orignal 32.31 KB Preview | Download
Dunster2016_Nondimensional_Model.cps Curated (nondimensional) model COPASI file. Figure 4 simulation results reproduced. 85.55 KB Preview | Download
Dunster2016_Dimensional_Model.cps Model COPASI file for dimensional model. 97.54 KB Preview | Download

  • Model originally submitted by : Matthew Roberts
  • Submitted: 14-Aug-2018 14:32:35
  • Last Modified: 26-Mar-2020 14:50:50
Revisions
  • Version: 4 public model Download this version
    • Submitted on: 26-Mar-2020 14:50:50
    • Submitted by: Ahmad Zyoud
    • With comment: Automatically added model identifier BIOMD0000000925
  • Version: 2 public model Download this version
    • Submitted on: 14-Aug-2018 14:32:35
    • Submitted by: Matthew Roberts
    • With comment: Edited model metadata online.
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Curator's comment:
(added: 26 Mar 2020, 14:50:26, updated: 26 Mar 2020, 14:50:26)
All the figures within the Figure 4 has been successfully reproduced except of a slight shift in the Y-axis