Domain-Oriented Reduction of Rule-Based Network Models
From BioNetWiki
N. M. Borisov, A. S. Chistopolsky, J. R. Faeder, and B. N. Kholodenko. Domain-Oriented Reduction of Rule-Based Network models. Submitted to IET Systems Biology.
- Preprint
- Supplementary material
- A macro-enabled version is available from BioNetGen Distributions. Version 2.0.47alpha is the first version containing the macro module.
Contents |
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Using the Macro Module
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Basic Usage
In the Perl2 directory of the distribution, there is a file called MacroBNG2.pl, which is a replacement driver for BioNetGen that can be used to access the Macro module. The basic usage is
<path-to-BNG>/Perl2/MacroBNG2.pl [options] file.bngl
Two main options are used to access and control the Macro module.
MacroBNG2.pl --macro file.bngl
uses the Macro module to generate any network using the generate_network command. It will find and apply all reductions using the algorithm described in the preprint above.
MacroBNG2.pl --macro --nored A,B file.bngl
performs Macro reduction on the model in file.bngl omitting proteins A and B.
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Examples
Reducible network models from the Preprint Supplements.
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EGFR-like model
begin parameters
# Total concentrations
L_tot 100
R_tot 100
A_tot 100
B_tot 100
# Kinetic constants
k1 0.003
k_1 0.18
k2 0.01
k_2 3.0
k3 0.6
k_3 0.4
k4 0.4
k_4 0.6
k5 0.03
k_5 1
k6 0.03
k_6 1
k7 0.3
k_7 0.7
k8 0.7
k_8 0.3
end parameters
begin species
L(r) L_tot # Ligand
R(r1,r2,r3~Y,r4~Y) R_tot # Receptor
# r1 on R is the ligand-binding site
# r2 on R is the dimerization site
# r3 on R is the tyrosine residue for binding the adapter A
# r4 on R is the tyrosine residue for binding the adapter B
A(r) A_tot # Non-scaffolding adaptor
B(b1,b2~Y,b3~Y) B_tot # Scaffolding adaptor
end species
begin reaction_rules
L(r) + R(r1) <-> L(r!1).R(r1!1) k1, k_1 # Ligand binding
L(r!1).R(r1!1,r2) + L(r!2).R(r1!2,r2) <-> \
L(r!1).R(r1!1,r2!3).L(r!2).R(r1!2,r2!3) k2, k_2 # Dimerization
R(r2!+,r3~Y) -> R(r2!+,r3~pY) k3 # Receptor phosphorylation at site r3
R(r3~pY) -> R(r3~Y) k_3 # Receptor dephosphorylation at site r3
R(r2!+,r4~Y) -> R(r2!+,r4~pY) k4 # Receptor phosphorylation at site r4
R(r4~pY) -> R(r4~Y) k_4 # Receptor dephosphorylation at site r4
R(r3~pY) + A(r) <-> R(r3~pY!1).A(r!1) k5, k_5 # Binding adapter A
R(r4~pY) + B(b1) <-> R(r4~pY!1).B(b1!1) k6, k_6 # Binding adapter B
B(b1!+,b2~Y) -> B(b1!+,b2~pY) k7 # Adaptor B phosphorylation at site b2
B(b2~pY) -> B(b2~Y) k_7 # Adaptor B dephosphorylation at site b2
B(b1!+,b3~Y) -> B(b1!+,b3~pY) k8 # Adaptor B phosphorylation at site b3
B(b3~pY) -> B(b3~Y) k_8 # Adaptor B dephosphorylation at site b3
end reaction_rules
begin observables
Molecules L_tot L
Molecules R_tot R
Molecules A_tot A
Molecules B_tot B
Molecules R_dim R.R
Molecules Abound A(r!+)
Molecules B1pY B(b2~pY)
Molecules B2pY B(b3~pY)
end observables
generate_network({overwrite=>1});
simulate_ode({t_end=>40,n_steps=>40,atol=>1e-8,rtol=>1e-8,sparse=>1});
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FceRI-like model
begin parameters
# Total concentrations
L_tot 100
R_tot 100
A_tot 100
B_tot 100
# Kinetic constants
k1 0.003
k_1 0.18
k2 0.01
k_2 3.0
k3 0.6
k_3 0.4
k4 0.4
k_4 0.6
k5 0.03
k_5 1
k6 0.03
k_6 1
k7 0.3
k_7 0.7
k8 0.7
k_8 0.3
end parameters
begin species
L(r) L_tot # Ligand
R(r1,r2,r3~Y,r4~Y) R_tot # Receptor
# r1 on R is the ligand-binding site
# r2 on R is the dimerization site
# r3 on R is the tyrosine residue for binding the adaptor A
# r4 on R is the tyrosine residue for binding the adaptor B
A(r) A_tot # Non-scaffolding adaptor
B(b1,b2~Y,b3~Y) B_tot # Scaffolding adaptor
end species
begin reaction_rules
L(r) + R(r1) <-> L(r!1).R(r1!1) k1, k_1 # Ligand binding
L(r!1).R(r1!1,r2) + L(r!2).R(r1!2,r2) <-> \
L(r!1).R(r1!1,r2!3).L(r!2).R(r1!2,r2!3) k2, k_2 # Dimirization
R(r2!+,r3~Y) -> R(r2!+,r3~pY) k3 # Receptor phosphorylation at site r3
R(r3~pY) -> R(r3~Y) k_3 # Receptor dephosphorylation at site r3
R(r2!+,r4~Y) -> R(r2!+,r4~pY) k4 # Receptor phosphorylation at site r4
R(r4~pY) -> R(r4~Y) k_4 # Receptor dephosphorylation at site r4
R(r3~pY) + A(r) <-> R(r3~pY!1).A(r!1) k5, k_5 # Binding adapter A
R(r4~pY) + B(b1) <-> R(r4~pY!1).B(b1!1) k6, k_6 # Binding adapter B
B(b1!+,b2~Y) -> B(b1!+,b2~pY) k7 # Adaptor B phosphorylation at site b2
B(b2~pY) -> B(b2~Y) k_7 # Adaptor B dephosphorylation at site b2
B(b1!+,b3~Y) -> B(b1!+,b3~pY) k8 # Adaptor B phosphorylation at site b3
B(b3~pY) -> B(b3~Y) k_8 # Adaptor B dephosphorylation at site b3
end reaction_rules
begin observables
Molecules L_tot L
Molecules R_tot R
Molecules A_tot A
Molecules B_tot B
Molecules R_dim R.R
Molecules Abound A(r!+)
Molecules B1pY B(b2~pY)
Molecules B2pY B(b3~pY)
end observables
generate_network({overwrite=>1});
simulate_ode({t_end=>40,n_steps=>40,atol=>1e-8,rtol=>1e-8,sparse=>1});
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