Makin2013 - Blood coagulation cascade model
Mathematical model of the blood coagulation system including lipid binding sites, meizothrombin, thrombomodulin, cleaved and light peptide chain Va species and Heparin.
- A hybrid-system model of the coagulation cascade: simulation, sensitivity, and validation.
- Makin JG, Narayanan S
- Journal of bioinformatics and computational biology , 10/ 2013 , Volume 11 , Issue 5 , pages: 1342004
- Department of Electrical Engineering and Computer Science, University of California, Berkeley, USA , International Computer Science Institute, Berkeley, CA 94720, USA.
- The process of human blood clotting involves a complex interaction of continuous-time/continuous-state processes and discrete-event/discrete-state phenomena, where the former comprise the various chemical rate equations and the latter comprise both threshold-limited behaviors and binary states (presence/absence of a chemical). Whereas previous blood-clotting models used only continuous dynamics and perforce addressed only portions of the coagulation cascade, we capture both continuous and discrete aspects by modeling it as a hybrid dynamical system. The model was implemented as a hybrid Petri net, a graphical modeling language that extends ordinary Petri nets to cover continuous quantities and continuous-time flows. The primary focus is simulation: (1) fidelity to the clinical data in terms of clotting-factor concentrations and elapsed time; (2) reproduction of known clotting pathologies; and (3) fine-grained predictions which may be used to refine clinical understanding of blood clotting. Next we examine sensitivity to rate-constant perturbation. Finally, we propose a method for titrating between reliance on the model and on prior clinical knowledge. For simplicity, we confine these last two analyses to a critical purely-continuous subsystem of the model.
|Makin2013.xml||SBML L2V4 representation of Makin2013 - Blood coagulation cascade model||182.96 KB||Preview | Download|
|Makin2013.cps||Model COPASI file. Makin2013 used model from PhD thesis (2008). Reactions and kinetic rates taken from tables 5.1, 5.2 and 5.3. Initial conditions from table 5.4. Thrombin peak (70pM) occurs at about 300s.||399.15 KB||Preview | Download|