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RuleWorld / bionetgen

Rule-based modeling framework
https://bionetgen.org/
MIT License
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Compartment volumes cannot be functions #119

Open GoogleCodeExporter opened 9 years ago

GoogleCodeExporter commented 9 years ago 
Compartment volumes cannot be defined as functions that can change in time. 
This makes it difficult to model scenarios such as cell growth or endocytosis.

Note that BNG does actually allow the volume entry in the "compartments" block 
to be a function, but that function gets evaluated to a number in 
pre-processing. Thus, it never changes.

Original issue reported on code.google.com by lh64@cornell.edu on 21 Jan 2014 at 9:45

dweindl commented 3 years ago

Hi, is there any way to keep bionetgen from evaluating compartment size parameters or functions and instead keep the respective symbol in the rate expression? Is there a reason for evaluating the compartment parameter / function?

wshlavacek commented 3 years ago

I don't know the answer, but if there isn't a workaround, you can simply avoid using cBNGL for model setup (unless you're also trying to use the eBNGL features). With plain BNGL, compartments are considered implicitly. I'm pasting below a simple example, in case it might be helpful. --Bill

begin model

References:

- Diamante LM, Lan T (2014) J Food Processing 2014: 234583.

begin parameters

fraction of a cell to be considered

f 1 # dimensionless (0<f<=1)

We will assume no cell growth (i.e., volumes are constant).

pi=2*asin(1) # dimensionless ratio

Avogadro constant

NA 6.02214076e23 # molec/mol (exact value)

Temp 37+273.15 # K (physiological temperature)

viscosities of the cytosol (H2O) and plasma membrane (lipid)

mu_H2O=2.414e-2*10^(247.8/(Temp-140)) # mPa s (0.69 mPa s)

mu_lipid 34.1 # mPa s viscosity of olive oil @ 38 degrees C (Diamante and Lan, 2014)

cellDiameter 2e-4 # dm (20 microns)

Area=pi*cellDiameter^2 # dm^2 per cell

height of thin layer adjacent to cytoplasmic side of plasma membrane

height 50e-9 # dm (5 nm)

effective volume of thin layer

Vlayer=fAreaheight*(mu_lipid/mu_H2O) # L per cell

Reactants embedded in or tethered to the plasma membrane diffuse more

slowly

than when they are free in the cytosol, which slows bimolecular

reactions.

We account for this effect by adjusting the thin layer volume by the

relative

viscosities of the lipid membrane and the cytosol (water).

cell density (cells are in suspension)

cellDensity 1e9 # cells/L (1e6 cells per mL)

volume of extracellular fluid surrounding a single cell (on average)

Vecf=f*1/cellDensity # L/cell

volume of cytoplasm

Vcyt f*1e-12 # L/cell (1 pL)

volume of nucleus

Vnuc f*5e-13 # L/cell (0.5 pL)

initial abundances of ligand, receptor, and TF

L_conc 0.5e-9 # M (0.5 nM)

L_init=L_conc(NAVecf) # M converted to molec/cell

R_init f*1e5 # molec/cell

TF_init f*5e4 # molec/cell

forward and reverse rate constants for ligand-receptor binding

kp1 1e7/(NA*Vecf) # /M/s converted to /(molec/cell)/s

km1 1e-2 # /s

rate constant for receptor internalization and recycling to plasma

membrane

krecycle 1/60 # /s

forward and reverse rate constants for receptor-TF binding

kp2_3D 1e6/(NA*Vcyt) # /M/s converted to /(molec/cell)/s

kp2_2D=kp2_3D*(Vcyt/Vlayer) # /(molec/cell)/s

km2 1e-1 # /s

rate constants for TF phosphorylation and dephosphorylation

kphos 0.1 # /s

kdephos 0.05 # /s

forward and reverse rate constants for TF dimerization

kdim_3D_cyt 5e6/(NA*Vcyt) # /M/s converted to /(molec/cell)/s

kdim_2D_ipm=kdim_3D_cyt*(Vcyt/Vlayer) # /(molec/cell)/s

kdim_3D_nuc=kdim_3D_cyt*(Vcyt/Vnuc) # /(molec/cell)/s

kdiss 0.2 # /s

rate parameters for mRNA synthesis

ksynth f*0.5 # molec/s

K50 f*10 # molec

rate constant for mRNA turnover

kdeg 0.01 # /s

transfer rate constants

kCytNuc_TF 0.01 # /s

kNucCyt_TF 0.05 # /s

kNucCyt_mRNA 0.05 # /s

end parameters

begin molecule types

L(r) # ligand

R(l,t) # receptor

TF(r,a~0~P,loc~cyt~nuc) # transcription factor

mRNA(loc~cyt~nuc) # mRNA

end molecule types

begin seed species

L(r) L_init

R(l,t) R_init

TF(r,a~0,loc~cyt) TF_init*(kNucCyt_TF/(kCytNuc_TF+kNucCyt_TF))

TF(r,a~0,loc~nuc) TF_init*(kCytNuc_TF/(kCytNuc_TF+kNucCyt_TF))

mRNA(loc~nuc) 0

end seed species

begin observables

Molecules total_ligand L()

Molecules total_receptor R()

Molecules total_TF TF()

Molecules Lfree L(r)

Molecules Rfree R(l)

Molecules LboundR R(l!+)

Molecules inactiveTF TF(a~0!?)

Molecules pTF_all TF(a~P!?)

Molecules pTF_allMonomers TF(a~P)

Species all_dimers_of_pTF TF(a~P!1).TF(a~P!1)

Molecules all_pTF_in_cyt TF(a~P!?,loc~cyt)

Molecules all_pTR_in_nuc TF(a~P!?,loc~nuc)

Molecules IllegalDimers TF(a~P!1,loc~cyt).TF(a~P!1,loc~nuc) # should be 0 abundance

Molecules RrecruitedTF TF(r!+)

Molecules cytTF TF(loc~cyt)

Molecules nucTF TF(loc~nuc)

Species cytTFdimers TF(a~P!1,loc~cyt).TF(a~P!1,loc~cyt)

Species nucTFdimers TF(a~P!1,loc~nuc).TF(a~P!1,loc~nuc)

Molecules cyt_mRNA mRNA(loc~cyt)

Molecules nuc_mRNA mRNA(loc~nuc)

end observables

begin functions

totalTFdimers()=cytTFdimers+nucTFdimers

totalmRNA()=cyt_mRNA+nuc_mRNA

Vol_ratio()=Vcyt/Vlayer

synthesisRate()=ksynth*nucTFdimers^2/(K50^2+nucTFdimers^2)

end functions

begin reaction rules

##########################################################

reactions in the extracellular fluid (ECF) compartment

##########################################################

ligand-receptor binding

L(r)+R(l)<->L(r!1).R(l!1) kp1,km1 # kp1 is scaled by 1/Vecf

############################################################################

reactions in the cytosol and at the inner leaflet of the plasma membrane

############################################################################

ligand internalization via endocytosis

& ligand degradation

& recycling of receptor from endocytic compartments to the plasma

membrane

L(r!1).R(l!1)->R(l) krecycle

recruitment of monomeric TF to ligand-bound receptor

R(l!+,t)+TF(r,a~?,loc~cyt)->R(l!+,t!1).TF(r!1,a~?,loc~cyt) kp2_3D

kp2_3D is scaled by 1/Vcyt

recruitment of dimeric TF to receptor

R(l!+,t)+TF(r,a~P!1,loc~cyt).TF(r,a~P!1,loc~cyt)->\

R(l!+,t!2).TF(r!2,a~P!1,loc~cyt).TF(r,a~P!1,loc~cyt) kp2_3D

receptor crosslinking by dimeric TF

R(t!1).TF(r!1,a~P!2,loc~cyt).TF(r,a~P!2,loc~cyt)+R(l!+,t)->\

R(t!1).TF(r!1,a~P!2,loc~cyt).TF(r!3,a~P!2,loc~cyt).R(l!+,t!3) kp2_2D

kp2_2D is scaled by 1/Vipm

receptor-TF dissociation

R(t!1).TF(r!1)->R(t)+TF(r) km2

ligand-stimulated activating phosphorylation of receptor-bound monomeric

TF

R(l!+,t!1).TF(r!1,a~0)->R(l!+,t!1).TF(r!1,a~P) kphos

deactivation of monomeric TF (taken to occur only in cytosol)

TF(a~P,loc~cyt)->TF(a~0,loc~cyt) kdephos

TF dimerization at the plasma membrane

TF(r!+,a~P)+TF(r,a~P,loc~cyt)->TF(r!+,a~P!1).TF(r,a~P!1,loc~cyt) kdim_3D_cyt

kdim_3D_cyt is scaled by 1/Vcyt

TF(r!+,a~P)+TF(r!+,a~P,loc~cyt)->TF(r!+,a~P!1).TF(r!+,a~P!1,loc~cyt) kdim_2D_ipm

kdim_2D_ipm is scaled by 1/Vipm

TF dimerization in the cytosol

TF(r,a~P,loc~cyt)+TF(r,a~P,loc~cyt)->\

TF(r,a~P!1,loc~cyt).TF(r,a~P!1,loc~cyt) kdim_3D_cyt

TF dimer dissociation in the cytosolic compartment

TF(a~P!1,loc~cyt).TF(a~P!1,loc~cyt)->TF(a~P,loc~cyt)+TF(a~P,loc~cyt) kdiss

mRNA degradation (only occurs in the cytosol)

mRNA(loc~cyt)->0 kdeg

#######################

transport processes

#######################

TF moves from cytosol to nucleus

TF(r,a~?,loc~cyt)->TF(r,a~?,loc~nuc) kCytNuc_TF

TF(r,a~P!1,loc~cyt).TF(r,a~P!1,loc~cyt)->\

TF(r,a~P!1,loc~nuc).TF(r,a~P!1,loc~nuc) 10*kCytNuc_TF

TF moves from nucleus to cytosol

TF(a~?,loc~nuc)->TF(a~?,loc~cyt) kNucCyt_TF

TF(a~P!1,loc~nuc).TF(a~P!1,loc~nuc)->\

TF(a~P!1,loc~cyt).TF(a~P!1,loc~cyt) kNucCyt_TF

mRNA moves from nucleus to cytosol

mRNA(loc~nuc)->mRNA(loc~cyt) kNucCyt_mRNA

############################

reactions in the nucleus

############################

reversible TF dimerization

TF(a~P,loc~nuc)+TF(a~P,loc~nuc)<->\

TF(a~P!1,loc~nuc).TF(a~P!1,loc~nuc) kdim_3D_nuc,kdiss

kdim_3D_nuc is scaled by 1/Vnuc

saturable dimeric TF-dependent mRNA synthesis

0->mRNA(loc~nuc) synthesisRate()

end reaction rules

end model

begin actions

generate_network({overwrite=>1})

saveConcentrations()

simulate({suffix=>"ode",method=>"ode",t_end=>2500,n_steps=>250, print_functions=>1})

resetConcentrations()

simulate({suffix=>"ssa",method=>"ssa",t_end=>2500,n_steps=>250, print_functions=>1}) end actions

On Thu, Feb 4, 2021 at 2:13 PM Daniel Weindl notifications@github.com wrote:

Hi, is there any way to keep bionetgen from evaluating compartment size parameters or functions and instead keep the respective symbol in the rate expression? Is there a reason for evaluating the compartment parameter / function?

— You are receiving this because you are subscribed to this thread. Reply to this email directly, view it on GitHub https://github.com/RuleWorld/bionetgen/issues/119#issuecomment-773606960, or unsubscribe https://github.com/notifications/unsubscribe-auth/AETOR5Z4DUR66FLA2ZAC5QDS5MEWFANCNFSM4XDR6C2A .

dweindl commented 3 years ago

Thanks for your suggestion @wshlavacek. This is for sure an option.

Would be great though if there was a way to use cBNGL to generate (fully) symbolic rate expressions.