Journal of bioinformatics and computational biology 20130905 5
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 discre ...[more]
Project description:Mathematical model of the blood coagulation cascade including meizothrombin, protein C, thrombomodulin, factor VIIIa fragments, partially proteolyzed factor Va species and inactive factor Va 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:Blood coagulation model investigating effects of Xa-inhibitors (Rivaroxaban and Apixaban). Model is an extension of Pohl1994 and reduced from Wajima2009.
Encoding the model from the supplementary files results in 43 species, 82 reactions and 111 parameters. Including the drug (Xa-inhibitor) and drug-Xa complexes results in 46 species, 84 reactions and 115 parameters (+1 dummy variable to change inhibitory kinetic parameters depending on which drug is simulated). The publication lists there being 45 species, 84 reactions and 116 parameters. Publication figure 2 has 45 species present however the complex VIIa:Xa (reaction 51 involving Xa and VIIa) is not shown. This figure also has numerous small errors such as listing IXa:ATIII complex twice (instead of one being XIa:ATIII), not showing XIa:ATIII, typo ('Va' -> Va), typo (IXa + VIIIa -> IXA:'VIIa').
Rate laws for Xa-drug interactions were assumed to be mass action.
Project description:Diabetes is a multifactorial disorder and epigenetics changes are increasingly appreciated to influence the development of diabetic complications. Chromatin remodeling and histone acetylation are implicated in activation of the inflammatory response. Recently, histone deacetylase (HDAC) inhibitors (HDACi) have proved to reduce the severity of inflammatory diseases. We have previously shown that chromatin alterations regulated by HDACi in HepG2 cells stimulated by hyperglycemia reduced hepatic glucose production. In this study, we examined gene expression patterns using next generation sequencing. We show the pharmacological HDAC inhibitor VPA attenuates hyperglycemia induced gene expression, highlighting the relevance of complement and coagulation cascade. These findings reveal a novel mechanism of VPA protection against hyperglycemia induced hepatic gene expression changes, which might improve the therapeutic approaches for diabetes. Overall design: RNA-seq was performed to understand gene expression changes in HepG2 cells in response to hyperglycemia and valproic acid. Analyses were performed in triplicate.
Project description:Blood coagulation mathematical model derived from Chatterjee et al. (2010) and Hockin et al. (2002). Included various inhibitors: TFPI, ATIII, generic kallikrein inhibitor, C1-inhibitor, alpha1-antitrypsin and alpha2-antiplasmin.