def create_dummy_reactions(model, model_fba, unit_flux=None):
""" Creates the dummy reactions.
This also creates the corresponding flux parameters and flux assignments.
:param model:
:param model_fba:
:param unit_flux:
:return:
"""
ex_rids = utils.find_exchange_reactions(model_fba)
objects = []
for ex_rid, sid in ex_rids.items():
pid_flux = FLUX_PARAMETER_PREFIX + sid
rid_flux = DUMMY_REACTION_PREFIX + sid
objects.append(
# flux parameter: fluxe from fba (rate of reaction)
fac.Parameter(sid=pid_flux, value=1.0, constant=True, unit=unit_flux, sboTerm=FLUX_PARAMETER_SBO),
)
# dummy reaction (pseudoreaction)
fac.create_reaction(model, rid=rid_flux, reversible=False,
products={DUMMY_SPECIES_ID: 1}, sboTerm=DUMMY_REACTION_SBO,
formula='0 {}'.format(unit_flux))
# flux assignment rule
objects.append(
fac.AssignmentRule(pid_flux, value=rid_flux, sboTerm=FLUX_ASSIGNMENTRULE_SBO),
)
fac.create_objects(model, objects)
def create_update_reaction(model, sid, modifiers=None, formula="-{}"):
""" Creates the update reaction for a given species.
Creates the update parameter in the process.
:param model:
:param sid:
:param modifiers:
:param formula:
:return:
:rtype:
"""
if modifiers is None:
modifiers = []
rid_update = UPDATE_REACTION_PREFIX + sid
# format the formula
formula = formula.format(FLUX_PARAMETER_PREFIX + sid)
fac.create_reaction(model, rid=rid_update, sboTerm=UPDATE_REACTION_SBO,
reactants={sid: 1}, modifiers=modifiers,
formula=formula)
def create_exchange_reaction(model, species_id, exchange_type=EXCHANGE, flux_unit=None):
""" Factory method to create exchange reactions for species in the FBA model.
Creates the exchange reaction, the upper and lower bounds,
and the ports.
:param model:
:param species_id:
:param exchange_type:
:param flux_unit:
:return:
"""
if exchange_type not in [EXCHANGE, EXCHANGE_IMPORT, EXCHANGE_EXPORT]:
raise ValueError("Wrong exchange_type: {}".format(exchange_type))
# id (e.g. EX_A)
ex_rid = EXCHANGE_REACTION_PREFIX + species_id
lb_id = LOWER_BOUND_PREFIX + ex_rid
ub_id = UPPER_BOUND_PREFIX + ex_rid
lb_value = LOWER_BOUND_DEFAULT
ub_value = UPPER_BOUND_DEFAULT
if exchange_type == EXCHANGE_IMPORT:
# negative flux through exchange reaction
ub_value = ZERO_BOUND
if exchange_type == EXCHANGE_EXPORT:
lb_value = ZERO_BOUND
parameters = [
fac.Parameter(sid=lb_id,
value=lb_value,
unit=flux_unit, constant=True, sboTerm=FLUX_BOUND_SBO),
fac.Parameter(sid=ub_id,
value=ub_value,
unit=flux_unit, constant=True, sboTerm=FLUX_BOUND_SBO),
]
fac.create_objects(model, parameters)
# exchange reactions are all reversible (it depends on the bounds in which direction they operate)
ex_r = fac.create_reaction(model, rid=ex_rid, reversible=True,
reactants={species_id: 1}, sboTerm=EXCHANGE_REACTION_SBO)
# exchange bounds
fbc.set_flux_bounds(ex_r, lb=lb_id, ub=ub_id)
# create ports
comp.create_ports(model, portType=comp.PORT_TYPE_PORT,
idRefs=[ex_rid, lb_id, ub_id])
return ex_r
def top_model(sbml_file, directory, emds, doc_fba, annotations=None):
""" Create top comp model.
Creates full comp model by combining fba, update and bounds
model with additional kinetics in the top model.
"""
top_notes = notes.format("""
<h2>TOP model</h2>
<p>Main comp DFBA model by combining fba, update and bounds
model with additional kinetics in the top model.</p>
""")
working_dir = os.getcwd()
os.chdir(directory)
doc = builder.template_doc_top(settings.MODEL_ID, emds)
model = doc.getModel()
utils.set_model_info(model,
notes=top_notes,
creators=creators,
units=units,
main_units=main_units)
# dt
builder.create_dfba_dt(model,
step_size=DT_SIM,
time_unit=UNIT_TIME,
create_port=False)
# compartment
compartment_id = "cell"
builder.create_dfba_compartment(model,
compartment_id=compartment_id,
unit_volume=UNIT_VOLUME,
create_port=False)
# dynamic species
model_fba = doc_fba.getModel()
builder.create_dfba_species(model,
model_fba,
compartment_id=compartment_id,
hasOnlySubstanceUnits=False,
unit_amount=UNIT_AMOUNT,
create_port=False)
# dummy species
builder.create_dummy_species(model,
compartment_id=compartment_id,
hasOnlySubstanceUnits=False,
unit_amount=UNIT_AMOUNT)
# exchange flux bounds
builder.create_exchange_bounds(model,
model_fba=model_fba,
unit_flux=UNIT_FLUX,
create_ports=False)
# dummy reactions & flux assignments
builder.create_dummy_reactions(model,
model_fba=model_fba,
unit_flux=UNIT_FLUX)
# replacedBy (fba reactions)
builder.create_top_replacedBy(model, model_fba=model_fba)
# replaced
builder.create_top_replacements(model,
model_fba,
compartment_id=compartment_id)
objects = [
# kinetic parameters
mc.Parameter(sid="Vmax_RATP", value=1, unit=UNIT_FLUX, constant=True),
mc.Parameter(sid='k_RATP',
value=0.1,
unit=UNIT_CONCENTRATION,
constant=True),
# balancing rules
mc.AssignmentRule(sid="atp_tot",
value="atp + adp",
unit=UNIT_CONCENTRATION),
mc.AssignmentRule(sid="c3_tot",
value="2 dimensionless * glc + pyr",
unit="mM")
]
mc.create_objects(model, objects)
ratp = mc.create_reaction(model,
rid="RATP",
name="atp -> adp",
fast=False,
reversible=False,
reactants={"atp": 1},
products={"adp": 1},
compartment=compartment_id,
formula='Vmax_RATP * atp/(k_RATP + atp)')
# initial concentrations for fba exchange species
initial_c = {'atp': 2.0, 'adp': 1.0, 'glc': 5.0, 'pyr': 0.0}
for sid, value in initial_c.items():
species = model.getSpecies(sid)
species.setInitialConcentration(value)
# write SBML file
if annotations:
annotator.annotate_sbml_doc(doc, annotations)
sbmlio.write_sbml(doc,
filepath=os.path.join(directory, sbml_file),
validate=True)
# change back the working dir
os.chdir(working_dir)
def fba_model(sbml_file, directory, annotations=None):
""" FBA model
:param sbml_file: output file name
:param directory: output directory
:return: SBMLDocument
"""
fba_notes = notes.format("""
<h2>FBA submodel</h2>
<p>DFBA fba submodel. Unbalanced metabolites are encoded via exchange fluxes.</p>
""")
doc = builder.template_doc_fba(settings.MODEL_ID)
model = doc.getModel()
utils.set_model_info(model,
notes=fba_notes,
creators=creators,
units=units,
main_units=main_units)
objects = [
# compartments
mc.Compartment(sid='cell',
value=1.0,
unit=UNIT_VOLUME,
constant=True,
name='cell',
spatialDimensions=3),
# exchange species
mc.Species(sid='atp',
name="ATP",
initialConcentration=0,
substanceUnit=UNIT_AMOUNT,
hasOnlySubstanceUnits=False,
compartment="cell"),
mc.Species(sid='adp',
name="ADP",
initialConcentration=0,
substanceUnit=UNIT_AMOUNT,
hasOnlySubstanceUnits=False,
compartment="cell"),
mc.Species(sid='glc',
name="Glucose",
initialConcentration=0,
substanceUnit=UNIT_AMOUNT,
hasOnlySubstanceUnits=False,
compartment="cell"),
mc.Species(sid='pyr',
name='Pyruvate',
initialConcentration=0,
substanceUnit=UNIT_AMOUNT,
hasOnlySubstanceUnits=False,
compartment="cell"),
# internal species
mc.Species(sid='fru16bp',
name='Fructose 1,6-bisphospate',
initialConcentration=0,
substanceUnit=UNIT_AMOUNT,
hasOnlySubstanceUnits=False,
compartment="cell"),
mc.Species(sid='pg2',
name='2-Phosphoglycerate',
initialConcentration=0,
substanceUnit=UNIT_AMOUNT,
hasOnlySubstanceUnits=False,
compartment="cell"),
# bounds
mc.Parameter(sid="ub_R3",
value=1.0,
unit=UNIT_FLUX,
constant=True,
sboTerm=builder.FLUX_BOUND_SBO),
mc.Parameter(sid="zero",
value=0.0,
unit=UNIT_FLUX,
constant=True,
sboTerm=builder.FLUX_BOUND_SBO),
mc.Parameter(sid="ub_default",
value=builder.UPPER_BOUND_DEFAULT,
unit=UNIT_FLUX,
constant=True,
sboTerm=builder.FLUX_BOUND_SBO),
]
mc.create_objects(model, objects)
# reactions
r1 = mc.create_reaction(model,
rid="R1",
name="glu + 2 atp -> fru16bp + 2 adp",
fast=False,
reversible=False,
reactants={
"glc": 1,
"atp": 2
},
products={
"fru16bp": 1,
'adp': 2
},
compartment='cell')
r2 = mc.create_reaction(model,
rid="R2",
name="fru16bp -> 2 pg2",
fast=False,
reversible=False,
reactants={"fru16bp": 1},
products={"pg2": 2},
compartment='cell')
r3 = mc.create_reaction(model,
rid="R3",
name="pg2 + adp -> pyr + atp",
fast=False,
reversible=False,
reactants={
"pg2": 1,
"adp": 2
},
products={
"pyr": 1,
"atp": 2
},
compartment='cell')
# flux bounds
fbc.set_flux_bounds(r1, lb="zero", ub="ub_default")
fbc.set_flux_bounds(r2, lb="zero", ub="ub_default")
fbc.set_flux_bounds(r3, lb="zero", ub="ub_R3")
# fbc.set_flux_bounds(ratp, lb="zero", ub="ub_RATP")
# exchange reactions
for sid in ['atp', 'adp', 'glc', 'pyr']:
builder.create_exchange_reaction(model,
species_id=sid,
flux_unit=UNIT_FLUX)
# objective function
model_fbc = model.getPlugin("fbc")
fbc.create_objective(model_fbc,
oid="RATP_maximize",
otype="maximize",
fluxObjectives={"R3": 1.0},
active=True)
if annotations:
annotator.annotate_sbml_doc(doc, annotations)
# write SBML
sbmlio.write_sbml(doc,
filepath=os.path.join(directory, sbml_file),
validate=True)
return doc
def top_model(sbml_file, directory, emds, doc_fba, annotations=None):
""" Create top comp model.
Creates full comp model by combining fba, update and bounds
model with additional kinetics in the top model.
"""
top_notes = notes.format("""
<h2>TOP model</h2>
<p>Main comp DFBA model by combining fba, update and bounds
model with additional kinetics in the top model.</p>
""")
working_dir = os.getcwd()
os.chdir(directory)
doc = builder.template_doc_top(settings.MODEL_ID, emds)
model = doc.getModel()
utils.set_model_info(model,
notes=top_notes,
creators=creators, units=units, main_units=main_units)
# dt
builder.create_dfba_dt(model, step_size=DT_SIM, time_unit=UNIT_TIME, create_port=False)
# compartment
compartment_id = "extern"
builder.create_dfba_compartment(model, compartment_id=compartment_id, unit_volume=UNIT_VOLUME, create_port=False)
# dynamic species
model_fba = doc_fba.getModel()
builder.create_dfba_species(model, model_fba, compartment_id=compartment_id, hasOnlySubstanceUnits=True,
unit_amount=UNIT_AMOUNT, create_port=False)
# dummy species
builder.create_dummy_species(model, compartment_id=compartment_id, hasOnlySubstanceUnits=True,
unit_amount=UNIT_AMOUNT)
# exchange flux bounds
builder.create_exchange_bounds(model, model_fba=model_fba, unit_flux=UNIT_FLUX, create_ports=False)
# dummy reactions & flux assignments
builder.create_dummy_reactions(model, model_fba=model_fba, unit_flux=UNIT_FLUX)
# replacedBy (fba reactions)
builder.create_top_replacedBy(model, model_fba=model_fba)
# replaced
builder.create_top_replacements(model, model_fba, compartment_id=compartment_id)
# initial concentrations for fba exchange species
initial_c = {
'A': 10.0,
'C': 0.0,
}
for sid, value in initial_c.items():
species = model.getSpecies(sid)
species.setInitialConcentration(value)
# kinetic model
mc.create_objects(model, [
# kinetic species
mc.Species(sid='D', initialConcentration=0, substanceUnit=UNIT_AMOUNT,
hasOnlySubstanceUnits=True, compartment="extern"),
# kinetic
mc.Parameter(sid="k_R4", value=0.1, constant=True, unit="per_s", sboTerm="SBO:0000009"),
# bounds parameter
mc.Parameter(sid='ub_R1', value=1.0, unit=UNIT_FLUX, constant=False, sboTerm="SBO:0000625"),
])
# kinetic reaction (MMK)
mc.create_reaction(model, rid="R4", name="R4: C -> D", fast=False, reversible=False,
reactants={"C": 1}, products={"D": 1}, formula="k_R4*C", compartment="extern")
# kinetic flux bounds
comp.replace_elements(model, 'ub_R1', ref_type=comp.SBASE_REF_TYPE_PORT,
replaced_elements={'bounds': ['ub_R1_port'],
'fba': ['ub_R1_port']})
# write SBML file
if annotations:
annotation.annotate_sbml_doc(doc, annotations)
sbmlio.write_sbml(doc, filepath=os.path.join(directory, sbml_file), validate=True)
# change back the working dir
os.chdir(working_dir)
def fba_model(sbml_file, directory, annotations=None):
""" FBA model
:param sbml_file: output file name
:param directory: output directory
:return: SBMLDocument
"""
fba_notes = notes.format("""
<h2>FBA submodel</h2>
<p>DFBA fba submodel. Unbalanced metabolites are encoded via exchange fluxes.</p>
""")
doc = builder.template_doc_fba(settings.MODEL_ID)
model = doc.getModel()
utils.set_model_info(model,
notes=fba_notes,
creators=creators,
units=units, main_units=main_units)
objects = [
# compartments
mc.Compartment(sid='extern', value=1.0, unit=UNIT_VOLUME, constant=True, name='external compartment',
spatialDimensions=3),
mc.Compartment(sid='cell', value=1.0, unit=UNIT_VOLUME, constant=True, name='cell', spatialDimensions=3),
mc.Compartment(sid='membrane', value=1.0, unit=UNIT_AREA, constant=True, name='membrane', spatialDimensions=2),
# exchange species
mc.Species(sid='A', name="A", initialConcentration=0, substanceUnit=UNIT_AMOUNT, hasOnlySubstanceUnits=True,
compartment="extern"),
mc.Species(sid='C', name="C", initialConcentration=0, substanceUnit=UNIT_AMOUNT, hasOnlySubstanceUnits=True,
compartment="extern"),
# internal species
mc.Species(sid='B1', name="B1", initialConcentration=0, substanceUnit=UNIT_AMOUNT, hasOnlySubstanceUnits=True,
compartment="cell"),
mc.Species(sid='B2', name="B2", initialConcentration=0, substanceUnit=UNIT_AMOUNT, hasOnlySubstanceUnits=True,
compartment="cell"),
# bounds
mc.Parameter(sid="ub_R1", value=1.0, unit=UNIT_FLUX, constant=True, sboTerm=builder.FLUX_BOUND_SBO),
mc.Parameter(sid="zero", value=0.0, unit=UNIT_FLUX, constant=True, sboTerm=builder.FLUX_BOUND_SBO),
mc.Parameter(sid="ub_default", value=builder.UPPER_BOUND_DEFAULT, unit=UNIT_FLUX, constant=True,
sboTerm=builder.FLUX_BOUND_SBO),
]
mc.create_objects(model, objects)
# reactions
r1 = mc.create_reaction(model, rid="R1", name="A import (R1)", fast=False, reversible=True,
reactants={"A": 1}, products={"B1": 1}, compartment='membrane')
r2 = mc.create_reaction(model, rid="R2", name="B1 <-> B2 (R2)", fast=False, reversible=True,
reactants={"B1": 1}, products={"B2": 1}, compartment='cell')
r3 = mc.create_reaction(model, rid="R3", name="B2 export (R3)", fast=False, reversible=True,
reactants={"B2": 1}, products={"C": 1}, compartment='membrane')
# flux bounds
fbc.set_flux_bounds(r1, lb="zero", ub="ub_R1")
fbc.set_flux_bounds(r2, lb="zero", ub="ub_default")
fbc.set_flux_bounds(r3, lb="zero", ub="ub_default")
# exchange reactions
builder.create_exchange_reaction(model, species_id="A", flux_unit=UNIT_FLUX)
builder.create_exchange_reaction(model, species_id="C", flux_unit=UNIT_FLUX)
# objective function
model_fbc = model.getPlugin("fbc")
fbc.create_objective(model_fbc, oid="R3_maximize", otype="maximize",
fluxObjectives={"R3": 1.0}, active=True)
# create ports for kinetic bounds
comp.create_ports(model, portType=comp.PORT_TYPE_PORT,
idRefs=["ub_R1"])
# write SBML
if annotations:
annotation.annotate_sbml_doc(doc, annotations)
sbmlio.write_sbml(doc, filepath=os.path.join(directory, sbml_file), validate=True)
return doc
def top_model(sbml_file, directory, emds, doc_fba, annotations=None):
""" Create top comp model.
Creates full comp model by combining fba, update and bounds
model with additional kinetics in the top model.
"""
top_notes = notes.format("""
<h2>TOP model</h2>
<p>Main comp DFBA model by combining fba, update and bounds
model with additional kinetics in the top model.</p>
""")
working_dir = os.getcwd()
os.chdir(directory)
doc = builder.template_doc_top(settings.MODEL_ID, emds)
model = doc.getModel()
utils.set_model_info(model,
notes=top_notes,
creators=creators,
units=units,
main_units=main_units)
# dt
builder.create_dfba_dt(model,
step_size=DT_SIM,
time_unit=UNIT_TIME,
create_port=False)
# compartment
compartment_id = "extern"
builder.create_dfba_compartment(model,
compartment_id=compartment_id,
unit_volume=UNIT_VOLUME,
create_port=False)
# dynamic species
model_fba = doc_fba.getModel()
builder.create_dfba_species(model,
model_fba,
compartment_id=compartment_id,
hasOnlySubstanceUnits=True,
unit_amount=UNIT_AMOUNT,
create_port=False)
# dummy species
builder.create_dummy_species(model,
compartment_id=compartment_id,
hasOnlySubstanceUnits=True,
unit_amount=UNIT_AMOUNT)
# exchange flux bounds
builder.create_exchange_bounds(model,
model_fba=model_fba,
unit_flux=UNIT_FLUX,
create_ports=False)
# dummy reactions & flux assignments
builder.create_dummy_reactions(model,
model_fba=model_fba,
unit_flux=UNIT_FLUX)
# replacedBy (fba reactions)
builder.create_top_replacedBy(model, model_fba=model_fba)
# replaced
builder.create_top_replacements(model,
model_fba,
compartment_id=compartment_id)
# initial concentrations for fba exchange species
initial_c = {
'A': 10.0,
'C': 0.0,
}
for sid, value in initial_c.items():
species = model.getSpecies(sid)
species.setInitialConcentration(value)
# kinetic model
mc.create_objects(
model,
[
# kinetic species
mc.Species(sid='D',
initialConcentration=0,
substanceUnit=UNIT_AMOUNT,
hasOnlySubstanceUnits=True,
compartment="extern"),
# kinetic
mc.Parameter(sid="k_R4",
value=0.1,
constant=True,
unit="per_s",
sboTerm="SBO:0000009"),
# bounds parameter
mc.Parameter(sid='ub_R1',
value=1.0,
unit=UNIT_FLUX,
constant=False,
sboTerm="SBO:0000625"),
])
# kinetic reaction (MMK)
mc.create_reaction(model,
rid="R4",
name="R4: C -> D",
fast=False,
reversible=False,
reactants={"C": 1},
products={"D": 1},
formula="k_R4*C",
compartment="extern")
# kinetic flux bounds
comp.replace_elements(model,
'ub_R1',
ref_type=comp.SBASE_REF_TYPE_PORT,
replaced_elements={
'bounds': ['ub_R1_port'],
'fba': ['ub_R1_port']
})
# write SBML file
if annotations:
annotator.annotate_sbml_doc(doc, annotations)
sbml.write_sbml(doc,
filepath=os.path.join(directory, sbml_file),
validate=True)
# change back the working dir
os.chdir(working_dir)
def fba_model(sbml_file, directory, annotations=None):
""" FBA model
:param sbml_file: output file name
:param directory: output directory
:return: SBMLDocument
"""
fba_notes = notes.format("""
<h2>FBA submodel</h2>
<p>DFBA fba submodel. Unbalanced metabolites are encoded via exchange fluxes.</p>
""")
doc = builder.template_doc_fba(settings.MODEL_ID)
model = doc.getModel()
utils.set_model_info(model,
notes=fba_notes,
creators=creators,
units=units,
main_units=main_units)
objects = [
# compartments
mc.Compartment(sid='extern',
value=1.0,
unit=UNIT_VOLUME,
constant=True,
name='external compartment',
spatialDimensions=3),
mc.Compartment(sid='cell',
value=1.0,
unit=UNIT_VOLUME,
constant=True,
name='cell',
spatialDimensions=3),
mc.Compartment(sid='membrane',
value=1.0,
unit=UNIT_AREA,
constant=True,
name='membrane',
spatialDimensions=2),
# exchange species
mc.Species(sid='A',
name="A",
initialConcentration=0,
substanceUnit=UNIT_AMOUNT,
hasOnlySubstanceUnits=True,
compartment="extern"),
mc.Species(sid='C',
name="C",
initialConcentration=0,
substanceUnit=UNIT_AMOUNT,
hasOnlySubstanceUnits=True,
compartment="extern"),
# internal species
mc.Species(sid='B1',
name="B1",
initialConcentration=0,
substanceUnit=UNIT_AMOUNT,
hasOnlySubstanceUnits=True,
compartment="cell"),
mc.Species(sid='B2',
name="B2",
initialConcentration=0,
substanceUnit=UNIT_AMOUNT,
hasOnlySubstanceUnits=True,
compartment="cell"),
# bounds
mc.Parameter(sid="ub_R1",
value=1.0,
unit=UNIT_FLUX,
constant=True,
sboTerm=builder.FLUX_BOUND_SBO),
mc.Parameter(sid="zero",
value=0.0,
unit=UNIT_FLUX,
constant=True,
sboTerm=builder.FLUX_BOUND_SBO),
mc.Parameter(sid="ub_default",
value=builder.UPPER_BOUND_DEFAULT,
unit=UNIT_FLUX,
constant=True,
sboTerm=builder.FLUX_BOUND_SBO),
]
mc.create_objects(model, objects)
# reactions
r1 = mc.create_reaction(model,
rid="R1",
name="A import (R1)",
fast=False,
reversible=True,
reactants={"A": 1},
products={"B1": 1},
compartment='membrane')
r2 = mc.create_reaction(model,
rid="R2",
name="B1 <-> B2 (R2)",
fast=False,
reversible=True,
reactants={"B1": 1},
products={"B2": 1},
compartment='cell')
r3 = mc.create_reaction(model,
rid="R3",
name="B2 export (R3)",
fast=False,
reversible=True,
reactants={"B2": 1},
products={"C": 1},
compartment='membrane')
# flux bounds
fbc.set_flux_bounds(r1, lb="zero", ub="ub_R1")
fbc.set_flux_bounds(r2, lb="zero", ub="ub_default")
fbc.set_flux_bounds(r3, lb="zero", ub="ub_default")
# exchange reactions
builder.create_exchange_reaction(model,
species_id="A",
flux_unit=UNIT_FLUX)
builder.create_exchange_reaction(model,
species_id="C",
flux_unit=UNIT_FLUX)
# objective function
model_fbc = model.getPlugin("fbc")
fbc.create_objective(model_fbc,
oid="R3_maximize",
otype="maximize",
fluxObjectives={"R3": 1.0},
active=True)
# create ports for kinetic bounds
comp.create_ports(model, portType=comp.PORT_TYPE_PORT, idRefs=["ub_R1"])
# write SBML
if annotations:
annotator.annotate_sbml_doc(doc, annotations)
sbml.write_sbml(doc,
filepath=os.path.join(directory, sbml_file),
validate=True)
return doc
def top_model(sbml_file, directory, emds, doc_fba=None, annotations=None):
"""
Create diauxic comp model.
Test script for working with the comp extension in SBML.
One model composition combines all the kinetic models,
in addition the higher level comp model is created which combines everything (i.e. the FBA & ODE models).
For the simulation of the full combined model the tools have to figure out the subparts which are
simulated with which simulation environment.
Creates the full comp model as combination of FBA and comp models.
The submodels must already exist in the given directory
"""
top_notes = notes.format("""
<h2>TOP model</h2>
<p>Main comp DFBA model by combining fba, update and bounds
model with additional kinetics in the top model.</p>
""")
# Necessary to change into directory with submodel files
working_dir = os.getcwd()
os.chdir(directory)
doc = builder.template_doc_top(settings.MODEL_ID, emds)
model = doc.getModel()
utils.set_model_info(model, notes=top_notes,
creators=creators, units=units, main_units=main_units)
# dt
builder.create_dfba_dt(model, time_unit=UNIT_TIME, create_port=False)
# compartment
compartment_id = "bioreactor"
builder.create_dfba_compartment(model, compartment_id=compartment_id, unit_volume=UNIT_VOLUME, create_port=False)
# dynamic species
model_fba = doc_fba.getModel()
builder.create_dfba_species(model, model_fba, compartment_id=compartment_id, unit_amount=UNIT_AMOUNT,
create_port=False)
# dummy species
builder.create_dummy_species(model, compartment_id=compartment_id, unit_amount=UNIT_AMOUNT)
# exchange flux bounds
builder.create_exchange_bounds(model, model_fba=model_fba, unit_flux=UNIT_FLUX, create_ports=False)
# dummy reactions & flux assignments
builder.create_dummy_reactions(model, model_fba=model_fba, unit_flux=UNIT_FLUX)
# replacedBy (fba reactions)
builder.create_top_replacedBy(model, model_fba=model_fba)
# replaced
builder.create_top_replacements(model, model_fba, compartment_id=compartment_id)
# initial kinetic concentrations
initial_c = {
'Glcxt': 10.8,
'Ac': 0.4,
'O2': 0.21,
'X': 0.001,
}
for sid, value in initial_c.items():
species = model.getSpecies(sid)
species.setInitialConcentration(value)
objects = [
# biomass conversion factor
# mc.Parameter(sid="Y", name="biomass [g_per_l]", value=1.0, unit="g_per_l"),
# oxygen exchange parameters
mc.Parameter(sid="O2_ref", name="O2 reference", value=0.21, unit=UNIT_CONCENTRATION),
mc.Parameter(sid="kLa", name="O2 mass transfer", value=7.5, unit='per_h'),
]
mc.create_objects(model, objects)
# oxygen transfer reaction
mc.create_reaction(model, rid="vO2_transfer", name="oxygen transfer", reversible=True,
reactants={}, products={"O2": 1}, formula="kLa * (O2_ref-O2) * bioreactor",
compartment="bioreactor")
# write SBML file
if annotations:
annotation.annotate_sbml_doc(doc, annotations)
sbmlio.write_sbml(doc, filepath=os.path.join(directory, sbml_file), validate=True)
# change back into working dir
os.chdir(working_dir)
def fba_model(sbml_file, directory, annotations=None):
""" Create FBA submodel.
FBA submodel in sbml:fbc-version 2.
"""
fba_notes = notes.format("""
<h2>FBA submodel</h2>
<p>DFBA fba submodel. Unbalanced metabolites are encoded via exchange fluxes.</p>
""")
doc = builder.template_doc_fba(settings.MODEL_ID)
model = doc.getModel()
utils.set_model_info(model, notes=fba_notes, creators=creators, units=units, main_units=main_units)
objects = [
# compartments
mc.Compartment(sid='bioreactor', value=1.0, unit=UNIT_VOLUME, constant=True, name='bioreactor',
spatialDimensions=3),
# species
mc.Species(sid='Glcxt', name="glucose", initialConcentration=0.0, substanceUnit=UNIT_AMOUNT, hasOnlySubstanceUnits=False,
compartment="bioreactor"),
mc.Species(sid='Ac', name="acetate", initialConcentration=0.0, substanceUnit=UNIT_AMOUNT, hasOnlySubstanceUnits=False,
compartment="bioreactor"),
mc.Species(sid='O2', name="oxygen", initialConcentration=0.0, substanceUnit=UNIT_AMOUNT, hasOnlySubstanceUnits=False,
compartment="bioreactor"),
mc.Species(sid='X', name="biomass", initialConcentration=0.0, substanceUnit=UNIT_AMOUNT, hasOnlySubstanceUnits=False,
compartment="bioreactor"),
# bounds
mc.Parameter(sid="zero", name="zero bound", value=0.0, unit=UNIT_FLUX_PER_G, constant=True, sboTerm="SBO:0000612"),
mc.Parameter(sid="ub_default", name="default upper bound", value=builder.UPPER_BOUND_DEFAULT, unit=UNIT_FLUX_PER_G,
constant=True, sboTerm="SBO:0000612"),
]
mc.create_objects(model, objects)
# reactions
r_v1 = mc.create_reaction(model, rid="v1", name="v1 (39.43 Ac + 35 O2 -> X)", reversible=False,
reactants={"Ac": 39.43, "O2": 35}, products={"X": 1}, compartment='bioreactor')
r_v2 = mc.create_reaction(model, rid="v2", name="v2 (9.46 Glcxt + 12.92 O2 -> X)", reversible=False,
reactants={"Glcxt": 9.46, "O2": 12.92}, products={"X": 1}, compartment='bioreactor')
r_v3 = mc.create_reaction(model, rid="v3", name="v3 (9.84 Glcxt + 12.73 O2 -> 1.24 Ac + X)", reversible=False,
reactants={"Glcxt": 9.84, "O2": 12.73}, products={"Ac": 1.24, "X": 1},
compartment='bioreactor')
r_v4 = mc.create_reaction(model, rid="v4", name="v4 (19.23 Glcxt -> 12.12 Ac + X)", reversible=False,
reactants={"Glcxt": 19.23}, products={"Ac": 12.12, "X": 1}, compartment='bioreactor')
# flux bounds: internal fluxes
fbc.set_flux_bounds(r_v1, lb="zero", ub="ub_default")
fbc.set_flux_bounds(r_v2, lb="zero", ub="ub_default")
fbc.set_flux_bounds(r_v3, lb="zero", ub="ub_default")
fbc.set_flux_bounds(r_v4, lb="zero", ub="ub_default")
# reactions: exchange reactions (this species can be changed by the FBA)
for sid in ['Ac', 'Glcxt', 'O2', 'X']:
builder.create_exchange_reaction(model, species_id=sid, flux_unit=UNIT_FLUX_PER_G,
exchange_type=builder.EXCHANGE)
# set bounds for the exchange reactions
p_lb_O2 = model.getParameter("lb_EX_O2")
p_lb_O2.setValue(-15.0) # FIXME: this is in mmol/gdw/h (biomass weighting of FBA)
p_lb_Glcxt = model.getParameter("lb_EX_Glcxt")
p_lb_Glcxt.setValue(-10.0) # FIXME: this is in mmol/gdw/h
# objective function
model_fba = model.getPlugin(builder.SBML_FBC_NAME)
fbc.create_objective(model_fba, oid="biomass_max", otype="maximize",
fluxObjectives={"v1": 1.0, "v2": 1.0, "v3": 1.0, "v4": 1.0})
# write SBML file
if annotations:
annotation.annotate_sbml_doc(doc, annotations)
sbmlio.write_sbml(doc, filepath=pjoin(directory, sbml_file), validate=True)
return doc
# internal species
Species(sid='B1', name="B1", initialAmount=0, substanceUnit=UNIT_AMOUNT, hasOnlySubstanceUnits=True,
compartment="cell"),
Species(sid='B2', name="B2", initialAmount=0, substanceUnit=UNIT_AMOUNT, hasOnlySubstanceUnits=True,
compartment="cell"),
# bounds
Parameter(sid="ub_R1", value=1.0, unit=UNIT_FLUX, constant=True, sboTerm=builder.FLUX_BOUND_SBO),
Parameter(sid="zero", value=0.0, unit=UNIT_FLUX, constant=True, sboTerm=builder.FLUX_BOUND_SBO),
Parameter(sid="ub_default", value=builder.UPPER_BOUND_DEFAULT, unit=UNIT_FLUX, constant=True,
sboTerm=builder.FLUX_BOUND_SBO),
]
factory.create_objects(model, objects)
# reactions
r1 = factory.create_reaction(model, rid="R1", name="A import (R1)", fast=False, reversible=True,
reactants={"A": 1}, products={"B1": 1}, compartment='membrane')
r2 = factory.create_reaction(model, rid="R2", name="B1 <-> B2 (R2)", fast=False, reversible=True,
reactants={"B1": 1}, products={"B2": 1}, compartment='cell')
r3 = factory.create_reaction(model, rid="R3", name="B2 export (R3)", fast=False, reversible=True,
reactants={"B2": 1}, products={"C": 1}, compartment='membrane')
# flux bounds
fbc.set_flux_bounds(r1, lb="zero", ub="ub_R1")
fbc.set_flux_bounds(r2, lb="zero", ub="ub_default")
fbc.set_flux_bounds(r3, lb="zero", ub="ub_default")
# exchange reactions
builder.create_exchange_reaction(model, species_id="A", flux_unit=UNIT_FLUX)
builder.create_exchange_reaction(model, species_id="C", flux_unit=UNIT_FLUX)
# objective function
def test_modelcreator_notebook():
"""
If this test fails the respective notebook must be updated:
:return:
"""
import libsbml
from libsbml import (UNIT_KIND_SECOND, UNIT_KIND_ITEM, UNIT_KIND_MOLE,
UNIT_KIND_KILOGRAM, UNIT_KIND_METRE, UNIT_KIND_LITRE)
from sbmlutils import comp
from sbmlutils import fbc
from sbmlutils import sbmlio
from sbmlutils import factory as fac
from sbmlutils.dfba import builder, utils
main_units = {
'time': 's',
'extent': UNIT_KIND_ITEM,
'substance': UNIT_KIND_ITEM,
'length': 'm',
'area': 'm2',
'volume': 'm3',
}
units = [
fac.Unit('s', [(UNIT_KIND_SECOND, 1.0)]),
fac.Unit('item', [(UNIT_KIND_ITEM, 1.0)]),
fac.Unit('kg', [(UNIT_KIND_KILOGRAM, 1.0)]),
fac.Unit('m', [(UNIT_KIND_METRE, 1.0)]),
fac.Unit('m2', [(UNIT_KIND_METRE, 2.0)]),
fac.Unit('m3', [(UNIT_KIND_METRE, 3.0)]),
fac.Unit('mM', [(UNIT_KIND_MOLE, 1.0, 0),
(UNIT_KIND_METRE, -3.0)]),
fac.Unit('per_s', [(UNIT_KIND_SECOND, -1.0)]),
fac.Unit('item_per_s', [(UNIT_KIND_ITEM, 1.0),
(UNIT_KIND_SECOND, -1.0)]),
fac.Unit('item_per_m3', [(UNIT_KIND_ITEM, 1.0),
(UNIT_KIND_METRE, -3.0)]),
]
UNIT_TIME = 's'
UNIT_AMOUNT = 'item'
UNIT_AREA = 'm2'
UNIT_VOLUME = 'm3'
UNIT_CONCENTRATION = 'item_per_m3'
UNIT_FLUX = 'item_per_s'
# Create SBMLDocument with fba
doc = builder.template_doc_fba(model_id="toy")
model = doc.getModel()
utils.set_units(model, units)
utils.set_main_units(model, main_units)
objects = [
# compartments
fac.Compartment(sid='extern', value=1.0, unit=UNIT_VOLUME, constant=True, name='external compartment',
spatialDimensions=3),
fac.Compartment(sid='cell', value=1.0, unit=UNIT_VOLUME, constant=True, name='cell', spatialDimensions=3),
fac.Compartment(sid='membrane', value=1.0, unit=UNIT_AREA, constant=True, name='membrane', spatialDimensions=2),
# exchange species
fac.Species(sid='A', name="A", value=0, substanceUnit=UNIT_AMOUNT, hasOnlySubstanceUnits=True,
compartment="extern"),
fac.Species(sid='C', name="C", value=0, substanceUnit=UNIT_AMOUNT, hasOnlySubstanceUnits=True,
compartment="extern"),
# internal species
fac.Species(sid='B1', name="B1", value=0, substanceUnit=UNIT_AMOUNT, hasOnlySubstanceUnits=True,
compartment="cell"),
fac.Species(sid='B2', name="B2", value=0, substanceUnit=UNIT_AMOUNT, hasOnlySubstanceUnits=True,
compartment="cell"),
# bounds
fac.Parameter(sid="ub_R1", value=1.0, unit=UNIT_FLUX, constant=True, sboTerm=builder.FLUX_BOUND_SBO),
fac.Parameter(sid="zero", value=0.0, unit=UNIT_FLUX, constant=True, sboTerm=builder.FLUX_BOUND_SBO),
fac.Parameter(sid="ub_default", value=builder.UPPER_BOUND_DEFAULT, unit=UNIT_FLUX, constant=True,
sboTerm=builder.FLUX_BOUND_SBO),
]
fac.create_objects(model, objects)
# reactions
r1 = fac.create_reaction(model, rid="R1", name="A import (R1)", fast=False, reversible=True,
reactants={"A": 1}, products={"B1": 1}, compartment='membrane')
r2 = fac.create_reaction(model, rid="R2", name="B1 <-> B2 (R2)", fast=False, reversible=True,
reactants={"B1": 1}, products={"B2": 1}, compartment='cell')
r3 = fac.create_reaction(model, rid="R3", name="B2 export (R3)", fast=False, reversible=True,
reactants={"B2": 1}, products={"C": 1}, compartment='membrane')
# flux bounds
fbc.set_flux_bounds(r1, lb="zero", ub="ub_R1")
fbc.set_flux_bounds(r2, lb="zero", ub="ub_default")
fbc.set_flux_bounds(r3, lb="zero", ub="ub_default")
# exchange reactions
builder.create_exchange_reaction(model, species_id="A", flux_unit=UNIT_FLUX)
builder.create_exchange_reaction(model, species_id="C", flux_unit=UNIT_FLUX)
# objective function
model_fbc = model.getPlugin("fbc")
fac.create_objective(model_fbc, oid="R3_maximize", otype="maximize",
fluxObjectives={"R3": 1.0}, active=True)
# write SBML file
import tempfile
sbml_file = tempfile.NamedTemporaryFile(suffix=".xml")
sbmlio.write_sbml(doc=doc, filepath=sbml_file.name)
unit=UNIT_FLUX,
constant=True,
sboTerm=builder.FLUX_BOUND_SBO),
Parameter(sid="ub_default",
value=builder.UPPER_BOUND_DEFAULT,
unit=UNIT_FLUX,
constant=True,
sboTerm=builder.FLUX_BOUND_SBO),
]
factory.create_objects(model, objects)
# reactions
r1 = factory.create_reaction(model,
rid="R1",
name="A import (R1)",
fast=False,
reversible=True,
reactants={"A": 1},
products={"B1": 1},
compartment='membrane')
r2 = factory.create_reaction(model,
rid="R2",
name="B1 <-> B2 (R2)",
fast=False,
reversible=True,
reactants={"B1": 1},
products={"B2": 1},
compartment='cell')
r3 = factory.create_reaction(model,
rid="R3",
name="B2 export (R3)",
fast=False,
def fba_model(sbml_file, directory, annotations=None):
""" FBA model
:param sbml_file: output file name
:param directory: output directory
:return: SBMLDocument
"""
fba_notes = notes.format("""
<h2>FBA submodel</h2>
<p>DFBA fba submodel. Unbalanced metabolites are encoded via exchange fluxes.</p>
""")
doc = builder.template_doc_fba(settings.MODEL_ID)
model = doc.getModel()
utils.set_model_info(model,
notes=fba_notes,
creators=creators,
units=units, main_units=main_units)
objects = [
# compartments
mc.Compartment(sid='cell', value=1.0, unit=UNIT_VOLUME, constant=True, name='cell', spatialDimensions=3),
# exchange species
mc.Species(sid='atp', name="ATP", initialConcentration=0, substanceUnit=UNIT_AMOUNT, hasOnlySubstanceUnits=False, compartment="cell"),
mc.Species(sid='adp', name="ADP", initialConcentration=0, substanceUnit=UNIT_AMOUNT, hasOnlySubstanceUnits=False, compartment="cell"),
mc.Species(sid='glc', name="Glucose", initialConcentration=0, substanceUnit=UNIT_AMOUNT, hasOnlySubstanceUnits=False, compartment="cell"),
mc.Species(sid='pyr', name='Pyruvate', initialConcentration=0, substanceUnit=UNIT_AMOUNT, hasOnlySubstanceUnits=False, compartment="cell"),
# internal species
mc.Species(sid='fru16bp', name='Fructose 1,6-bisphospate', initialConcentration=0, substanceUnit=UNIT_AMOUNT, hasOnlySubstanceUnits=False, compartment="cell"),
mc.Species(sid='pg2', name='2-Phosphoglycerate', initialConcentration=0, substanceUnit=UNIT_AMOUNT, hasOnlySubstanceUnits=False, compartment="cell"),
# bounds
mc.Parameter(sid="ub_R3", value=1.0, unit=UNIT_FLUX, constant=True, sboTerm=builder.FLUX_BOUND_SBO),
mc.Parameter(sid="zero", value=0.0, unit=UNIT_FLUX, constant=True, sboTerm=builder.FLUX_BOUND_SBO),
mc.Parameter(sid="ub_default", value=builder.UPPER_BOUND_DEFAULT, unit=UNIT_FLUX, constant=True,
sboTerm=builder.FLUX_BOUND_SBO),
]
mc.create_objects(model, objects)
# reactions
r1 = mc.create_reaction(model, rid="R1", name="glu + 2 atp -> fru16bp + 2 adp", fast=False, reversible=False,
reactants={"glc": 1, "atp": 2}, products={"fru16bp": 1, 'adp': 2}, compartment='cell')
r2 = mc.create_reaction(model, rid="R2", name="fru16bp -> 2 pg2", fast=False, reversible=False,
reactants={"fru16bp": 1}, products={"pg2": 2}, compartment='cell')
r3 = mc.create_reaction(model, rid="R3", name="pg2 + adp -> pyr + atp", fast=False, reversible=False,
reactants={"pg2": 1, "adp": 2}, products={"pyr": 1, "atp": 2}, compartment='cell')
# flux bounds
fbc.set_flux_bounds(r1, lb="zero", ub="ub_default")
fbc.set_flux_bounds(r2, lb="zero", ub="ub_default")
fbc.set_flux_bounds(r3, lb="zero", ub="ub_R3")
# fbc.set_flux_bounds(ratp, lb="zero", ub="ub_RATP")
# exchange reactions
for sid in ['atp', 'adp', 'glc', 'pyr']:
builder.create_exchange_reaction(model, species_id=sid, flux_unit=UNIT_FLUX)
# objective function
model_fbc = model.getPlugin("fbc")
fbc.create_objective(model_fbc, oid="RATP_maximize", otype="maximize", fluxObjectives={"R3": 1.0}, active=True)
if annotations:
annotation.annotate_sbml_doc(doc, annotations)
# write SBML
sbmlio.write_sbml(doc, filepath=os.path.join(directory, sbml_file), validate=True)
return doc
def top_model(sbml_file, directory, emds, doc_fba, annotations=None):
""" Create top comp model.
Creates full comp model by combining fba, update and bounds
model with additional kinetics in the top model.
"""
top_notes = notes.format("""
<h2>TOP model</h2>
<p>Main comp DFBA model by combining fba, update and bounds
model with additional kinetics in the top model.</p>
""")
working_dir = os.getcwd()
os.chdir(directory)
doc = builder.template_doc_top(settings.MODEL_ID, emds)
model = doc.getModel()
utils.set_model_info(model,
notes=top_notes,
creators=creators, units=units, main_units=main_units)
# dt
builder.create_dfba_dt(model, step_size=DT_SIM, time_unit=UNIT_TIME, create_port=False)
# compartment
compartment_id = "cell"
builder.create_dfba_compartment(model, compartment_id=compartment_id, unit_volume=UNIT_VOLUME, create_port=False)
# dynamic species
model_fba = doc_fba.getModel()
builder.create_dfba_species(model, model_fba, compartment_id=compartment_id, hasOnlySubstanceUnits=False,
unit_amount=UNIT_AMOUNT, create_port=False)
# dummy species
builder.create_dummy_species(model, compartment_id=compartment_id, hasOnlySubstanceUnits=False,
unit_amount=UNIT_AMOUNT)
# exchange flux bounds
builder.create_exchange_bounds(model, model_fba=model_fba, unit_flux=UNIT_FLUX, create_ports=False)
# dummy reactions & flux assignments
builder.create_dummy_reactions(model, model_fba=model_fba, unit_flux=UNIT_FLUX)
# replacedBy (fba reactions)
builder.create_top_replacedBy(model, model_fba=model_fba)
# replaced
builder.create_top_replacements(model, model_fba, compartment_id=compartment_id)
objects = [
# kinetic parameters
mc.Parameter(sid="Vmax_RATP", value=1, unit=UNIT_FLUX, constant=True),
mc.Parameter(sid='k_RATP', value=0.1, unit=UNIT_CONCENTRATION, constant=True),
# balancing rules
mc.AssignmentRule(sid="atp_tot", value="atp + adp", unit=UNIT_CONCENTRATION),
mc.AssignmentRule(sid="c3_tot", value="2 dimensionless * glc + pyr", unit="mM")
]
mc.create_objects(model, objects)
ratp = mc.create_reaction(model, rid="RATP", name="atp -> adp", fast=False, reversible=False,
reactants={"atp": 1}, products={"adp": 1}, compartment=compartment_id,
formula='Vmax_RATP * atp/(k_RATP + atp)')
# initial concentrations for fba exchange species
initial_c = {
'atp': 2.0,
'adp': 1.0,
'glc': 5.0,
'pyr': 0.0
}
for sid, value in initial_c.items():
species = model.getSpecies(sid)
species.setInitialConcentration(value)
# write SBML file
if annotations:
annotation.annotate_sbml_doc(doc, annotations)
sbmlio.write_sbml(doc, filepath=os.path.join(directory, sbml_file), validate=True)
# change back the working dir
os.chdir(working_dir)