Analysis of complex time-dependent biological networks is an important challenge in the current postgenomic era. We propose a middle-out approach for decomposition and analysis of complex time-dependent biological networks based on: 1), creation of a detailed mechanism-driven mathematical model of the network; 2), network response decomposition into several physiologically relevant subtasks; and 3), subsequent decomposition of the model, with the help of task-oriented necessity and sensitivity a ...[more]
Project description:Mathematical model of blood coagulation investigating effects of varied factor VIIa on thrombin generation. Model derived from Hockin2002/Butenas2004. Butenas added two new reactions (R28 and R29) and two new parameters (k43 and k44). Here, changes to parameters k32 and k38 and TF initial conc. changed to 5e-12
Project description:Mathematical model of the blood coagulation cascade. Extended Hockin model with contributions from Kim2007, Naski1991, Schneider2004, Horrevoets1996, Brummel-Ziedins2012, Mitrophanov2012, Danforth2009 and Hekman1988. Model incorporates more fibrin associated species such as fibrin I and II monomers and fibrinopeptide A and B as well as factor V fragments.
Project description:Mathematical model of blood coagulation. Reused Wajima2009 model with modifications to reactions 27 (formation of Va:Xa complex), 32 (Xa inhibition by TFPI) and 45 (Xa inhibition by TFPI-Heparin complex) as described in publication equations 2,3 and 4. Publication lists parameter sets to simulate Rivaroxaban, VKA and Enoxaparin (supplementary files).
Project description:Cancer patients often have an activated clotting system and are at increased risk for venous thrombosis. In this study, we analyzed tissue factor (TF) expression in four different human pancreatic tumor cell lines for the purpose of producing derivative tumors in vivo. We found that two of the lines expressed TF and released TF-positive microparticles (MPs) into the culture medium. The majority of TF protein in the culture medium was associated with MPs. Importantly, only TF-positive cell lines activated coagulation in nude mice, and this activation was abolished by an anti-human TF antibody. Of the two TF-positive lines only one produced detectable levels of human MP TF activity in the plasma when grown orthotopically in nude mice. Surprisingly, <5% of human TF protein in plasma from tumor-bearing mice was associated with MPs. Mice with TF-positive tumors and elevated levels of circulating TF-positive MPs had increased thrombosis in a saphenous vein model. In contrast, we observed no difference in thrombus weight between tumor bearing and control mice in an inferior vena cava stenosis model. Our studies suggest that in a xenograft mouse model tumor TF activates coagulation, whereas TF on circulating MPs may trigger venous thrombosis. Overall design: 8 human tumor pancreatic cell lines
Project description:Model listing the reactions of the intrinsic pathway as listed in Zarnitsina1996. Publication model is a spatio-termporal mathematical model of blood coagulation.
Model used as the example of the numerical intrinsic pathway in Braescu et al. (2011).
L. Braescu, M. Leretter, T. George, New direct inhibitors and their computed effect on the dynamics of thrombin formation in blood coagulation, in: T. F. George (Ed.), Computational Studies of New Materials II, World Scientific, 2011, 173–190. doi:10.3389/fphys.2012.00266.
Project description:Blood coagulation model using an updated Hockin2002 model. New reactions for factor X and V activation by IXa and mIIa respectively (reactions R28 and R29, parameters k43 and k44). Changes to parameters k32 and k38 (appendix not found for cited reference [Danforth 2009] so parameters from Mitrophanov2011 were used). Model introduces formula for adjusting kinetic rates for reduced temperatures.