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#15: Proteolytic cascade in human blood coagulation system

Description:
Proteolytic cascade in human blood coagulation system. Blood coagulation is a defense mechanism which prevent bleeding due to vessel damage by plug formation at the injury site. Any perturbation of the coagulation cascade can result in uncontrolled clotting or hemorrhage. The delicate regulatory system is controlled by a number of plasma protein-protein interactions as well as interaction with cellular receptors. Here, we present a primary blood coagulation model which is based on absolute minimal transformations involved in the process. The current model comprises of an extended set(108 in number) of molecular species and complexes. The model can be freely downloaded and used for further user specific investigation.

Model components | Rules | User instructions

1. Initial Parameters:

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1. M 1

1. N 0

1. kp1 1e1

1. km1 0.02

1. Parameters ends

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1. Initial Molecules

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1. II(loc~lip~flu,bs,state~u~a)

1. V(loc~lip~flu,bs2,bs10,state~u~a)

1. VII(loc~lip~flu,tf,bsf,state~u~a)

1. VIII(loc~lip~flu,pl,bs9,bs10,state~u~a)

1. X(loc~lip~flu,bs,state~u~a)

1. IX(loc~lip~flu,bs,state~u~a)

1. XI(loc~lip~flu,bs)

1. TF(bs)

1. AT(bs)

1. LPD()

1. Molecules ends

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1. Start Species

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1. II(loc~lip,at,bs,state~u) 1400

1. V(loc~lip,bs2,bs10,state~u) 20

1. VII(loc~lip,tf,bsf,state~a) 0.1

1. VIII(loc~lip,pl,bs9,bs10,state~u) 0.7

1. IX(loc~lip,at,bs,state~u) 90

1. X(loc~lip,at,bs,state~u). 170

1. XI(loc~lip,bs) 30

1. TF(bs) 0.005

1. AT(bs) 3400

1. LPD() M

1. Species ends

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1. Expanded Species (Model predicted)

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1. TF(bs!1).VII(bsf,loc~lip,state~a,tf!1) 0

1. VII(bsf!1,loc~lip,state~a,tf).X(at,bs!1,loc~lip,state~u) 0par

1. IX(at,bs!1,loc~lip,state~u).VII(bsf!1,loc~lip,state~a,tf) 0

1. VIII(bs10,bs9,loc~lip,pl,state~a) 0

1. V(bs10,bs2,loc~lip,state~a) 0

1. TF(bs!1).VII(bsf!2,loc~lip,state~a,tf!1).X(at,bs!2,loc~lip,state~u) 0

1. IX(at,bs!1,loc~lip,state~u).TF(bs!2).VII(bsf!1,loc~lip,state~a,tf!2) 0

1. VII(bsf!1,loc~lip,state~a,tf).X(at,bs!1,loc~lip,state~a) 0

1. IX(at,bs!1,loc~lip,state~a).VII(bsf!1,loc~lip,state~a,tf) 0

1. TF(bs!1).VII(bsf!2,loc~lip,state~a,tf!1).X(at,bs!2,loc~lip,state~a) 0

1. IX(at,bs!1,loc~lip,state~a).TF(bs!2).VII(bsf!1,loc~lip,state~a,tf!2) 0

1. AT(bs!1).IX(at!1,bs!2,loc~lip,state~a).VII(bsf!2,loc~lip,state~a,tf) 0

1. AT(bs!1).VII(bsf!2,loc~lip,state~a,tf).X(at!1,bs!2,loc~lip,state~a) 0

1. X(at,bs,loc~lip,state~a) 0

1. IX(at,bs,loc~lip,state~a) 0

1. AT(bs!1).IX(at!1,bs!2,loc~lip,state~a).TF(bs!3).VII(bsf!2,loc~lip,state~a,tf!3) 0

1. AT(bs!1).TF(bs!2).VII(bsf!3,loc~lip,state~a,tf!2).X(at!1,bs!3,loc~lip,state~a) 0

1. AT(bs!1).IX(at!1,bs,loc~lip,state~a) 0

1. AT(bs!1).X(at!1,bs,loc~lip,state~a) 0

1. IX(at,bs!1,loc~lip,state~a).VIII(bs10,bs9!1,loc~lip,pl,state~a) 0

1. V(bs10!1,bs2,loc~lip,state~a).X(at,bs!1,loc~lip,state~a) 0

1. AT(bs!1).IX(at!1,bs!2,loc~lip,state~a).VIII(bs10,bs9!2,loc~lip,pl,state~a) 0

1. AT(bs!1).V(bs10!2,bs2,loc~lip,state~a).X(at!1,bs!2,loc~lip,state~a) 0

1. IX(at,bs!1,loc~lip,state~a).VIII(bs10!2,bs9!1,loc~lip,pl,state~a).X(at,bs!2,loc~lip,state~u) 0

1. IX(at,bs!1,loc~lip,state~a).VIII(bs10!2,bs9!1,loc~lip,pl,state~a).X(at,bs!2,loc~lip,state~a) 0

1. AT(bs!1).IX(at,bs!2,loc~lip,state~a).VIII(bs10!3,bs9!2,loc~lip,pl,state~a).X(at!1,bs!3,loc~lip,state~a) 0

1. II(at,bs!1,loc~lip,state~u).V(bs10!2,bs2!1,loc~lip,state~a).X(at,bs!2,loc~lip,state~a) 0

1. AT(bs!1).IX(at!1,bs!2,loc~lip,state~a).VIII(bs10!3,bs9!2,loc~lip,pl,state~a).X(at,bs!3,loc~lip,state~u) 0

1. AT(bs!1).IX(at!1,bs!2,loc~lip,state~a).VIII(bs10!3,bs9!2,loc~lip,pl,state~a).X(at,bs!3,loc~lip,state~a) 0

1. AT(bs!1).AT(bs!2).IX(at!1,bs!3,loc~lip,state~a).VIII(bs10!4,bs9!3,loc~lip,pl,state~a).X(at!2,bs!4,loc~lip,state~a) 0

1. AT(bs!1).II(at,bs!2,loc~lip,state~u).V(bs10!3,bs2!2,loc~lip,state~a).X(at!1,bs!3,loc~lip,state~a) 0

1. VIII(bs10!1,bs9,loc~lip,pl,state~a).X(at,bs!1,loc~lip,state~u) 0

1. VIII(bs10!1,bs9,loc~lip,pl,state~a).X(at,bs!1,loc~lip,state~a) 0

1. AT(bs!1).VIII(bs10!2,bs9,loc~lip,pl,state~a).X(at!1,bs!2,loc~lip,state~a) 0

1. II(at,bs!1,loc~lip,state~a).V(bs10!2,bs2!1,loc~lip,state~a).X(at,bs!2,loc~lip,state~a) 0

1. AT(bs!1).II(at!1,bs!2,loc~lip,state~a).V(bs10!3,bs2!2,loc~lip,state~a).X(at,bs!3,loc~lip,state~a) 0

1. AT(bs!1).II(at,bs!2,loc~lip,state~a).V(bs10!3,bs2!2,loc~lip,state~a).X(at!1,bs!3,loc~lip,state~a) 0

1. AT(bs!1).AT(bs!2).II(at!1,bs!3,loc~lip,state~a).V(bs10!4,bs2!3,loc~lip,state~a).X(at!2,bs!4,loc~lip,state~a) 0

1. Expanded Species ends

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1. Rules

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1. II(bs,loc~flu) + LPD <-> II(bs,loc~lip) kp1,km1

1. IX(bs,loc~flu) + LPD <-> IX(bs,loc~lpd) kp1,km1

1. X(bs,loc~flu) + LPD <-> X(bs,loc~lip) kp1,km1

1. V(bs2,bs10,loc~flu) + LPD <-> V(bs2,bs10,loc~lip) kp1,km1

1. VII(bsf,loc~flu) + LPD <-> VII(bsf,loc~lpd) kp1,km1

1. VIII(bs9,bs10,,loc~flu) + LPD <-> VIII(bs9,bs10,loc~lip) kp1,km1

1. TF(bs) + VII(tf) <-> TF(bs!1).VII(tf!1) kp1,km1

1. AT(bs) + II(at,state~a) <-> AT(bs!1).II(at!1,state~a) kp1,km1

1. AT(bs) + IX(at,state~a) <-> AT(bs!1).IX(at!1,state~a) kp1,km1

1. AT(bs) + X(at,state~a) <-> AT(bs!1).X(at!1,state~a) kp1,km1

1. VII(state~a,bsf,loc~flu) + X(bs,loc~flu) <-> VII(state~a,bsf!1,loc~flu).X(bs!1,loc~flu) kp1,km1

1. VII(state~a,bsf,loc~lip) + X(bs,loc~lip) <-> VII(state~a,bsf!1,loc~lip).X(bs!1,loc~lip) kp1,km1

1. VII(state~a,bsf!1).X(bs!1,state~u) -> VII(state~a,bsf!1).X(bs!1,state~a) kp1

1. VII(state~a,bsf,loc~flu) + IX(bs,loc~flu) <-> VII(state~a,bsf!1,loc~flu).IX(bs!1,loc~flu) kp1,km1

1. VII(state~a,bsf,loc~lip) + IX(bs,loc~lip) <-> VII(state~a,bsf!1,loc~lip).IX(bs!1,loc~lip) kp1,km1

1. VII(state~a,bsf!1).IX(bs!1,state~u) -> VII(state~a,bsf!1).IX(bs!1,state~a) kp1

1. VIII(state~u) -> VIII(state~a) kp1

1. VIII(state~a,bs9,loc~lip) + IX(bs,state~a,loc~lip) <-> VIII(state~a,bs9!1,loc~lip).IX(bs!1,state~a,loc~lip) kp1,km1

1. VIII(state~a,bs9,loc~flu) + IX(bs,state~a,loc~flu) <-> VIII(state~a,bs9!1,loc~flu).IX(bs!1,state~a,loc~flu) kp1,km1

1. VIII(state~a,bs10,loc~lip) + X(bs,state~a,loc~lip) <-> VIII(state~a,bs10!1,loc~lip).X(bs!1,state~a,loc~lip) kp1,km1

1. VIII(state~a,bs10,loc~flu) + X(bs,state~a,loc~flu) <-> VIII(state~a,bs10!1,loc~flu).X(bs!1,state~a,loc~flu) kp1,km1

1. VIII(state~a,bs9!2,bs10!1).X(bs!1,state~u).IX(state~a,bs!2) -> VIII(state~a,bs9!2,bs10!1).X(bs!1,state~a).IX(state~a,bs!2) kp1

1. V(state~u) -> V(state~a) kp1

1. V(state~a,bs10,loc~lip) + X(state~a,bs,loc~lip) -> V(state~a,bs10!1,loc~lip).X(state~a,bs!1,loc~lip) kp1

1. V(state~a,bs10,loc~flu) + X(state~a,bs,loc~flu) -> V(state~a,bs10!1,loc~flu).X(state~a,bs!1,loc~flu) kp1

1. V(state~a,bs2,bs10!1,loc~lip).X(state~a,bs!1,loc~lip) + II(bs,loc~lip) -> V(state~a,bs2!2,bs10!1,loc~lip).X(state~a,bs!1,loc~lip).II(bs!2,loc~lip) kp1

1. V(state~a,bs2!2,bs10!1).X(state~a,bs!1).II(bs!2,state~u) -> V(state~a,bs2!2,bs10!1).X(state~a,bs!1).II(bs!2,state~a) kp1

1. Rules ends

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[ View in original version ]

Created on: Fri Sep 12 09:58:09 PDT 2008

Created by: ptalwar

Instructions

The current model for coagulation cascade encompasses the basic events involved in thrombin generation and various coagulation factors transformations. The user has the ability to download our quantitative rule based model from the PathwayDB pages for further modifications and extensions.

 
System requirements

Model format: BNGL

Analysis system: BioNetGen standalone or VirtualCell enviornment http://vcell.org/bionetgen.

 
Rule-based model file has the following structure

Each block in the model file starts with "begin" and ends with "end" keywords. There are mainly four blocks in BNGL file namely, 1) Parameters 2) Species 3) Reaction rules and 4) Observables.

 
Parameters Block

Parameters refer to numerical values for the variables that are associated with species(eg. molecular concentrations, M) and rules (eg. reaction rates, k).

Species Block

Species block refers to Seed species i.e. the species which are defined at the start of network generation. Each species which exist in different states(active/inactive) must be defined separately in the Species block. Each species name is defined as a structured object with all the associated components for example, binding sites, state of activity and localization information.

Observables Block

Observable block refers to the molecules and species that the user wish to map using the model understudy. Each observable is associated with the corresponding components.

Rules Block

Rules are the basic transformations that are needed for generating species and reactions in the rule-based model. Each line of a rule has reactant(s), an arrow(->,<->), product(s) and the reaction rates.

By definition, each rule generates single or multiple species(expanded species) and reactions.

These four blocks are the basic framework for defining a rule-based model. Once, the user defines the model, there are following commands which can be used to run the model:

generate_network (NET file)

simulate_ode (GDAT file)

writeSBML

 

In case of further queries,

please contact: Priti Talwar (E-mail:ptalwar at burnham dot org)