def add_default_flux_bounds(doc, lower=0.0, upper=100.0, unit='mole_per_s'):
""" Adds default flux bounds to SBMLDocument.
:param doc:
:type doc:
:param lower:
:type lower:
:param upper:
:type upper:
"""
# FIXME: overwrites lower/upper parameter (check if existing)
# TODO: the units are very specific (more generic)
warnings.warn('Adding default flux bounds', UserWarning)
model = doc.getModel()
parameters = [
factory.Parameter(sid='upper', value=upper, unit=unit),
factory.Parameter(sid='lower', value=lower, unit=unit),
]
factory.create_objects(model, parameters)
for r in model.reactions:
rfbc = r.getPlugin("fbc")
if not rfbc.isSetLowerFluxBound():
rfbc.setLowerFluxBound('lower')
if not rfbc.isSetUpperFluxBound():
rfbc.setUpperFluxBound('upper')
def add_default_flux_bounds(doc, lower=0.0, upper=100.0, unit='mole_per_s'):
""" Adds default flux bounds to SBMLDocument.
:param doc:
:type doc:
:param lower:
:type lower:
:param upper:
:type upper:
"""
# FIXME: overwrites lower/upper parameter (check if existing)
# TODO: the units are very specific (more generic)
warnings.warn('Adding default flux bounds', UserWarning)
model = doc.getModel()
parameters = [
factory.Parameter(sid='upper', value=upper, unit=unit),
factory.Parameter(sid='lower', value=lower, unit=unit),
]
factory.create_objects(model, parameters)
for r in model.reactions:
rfbc = r.getPlugin("fbc")
if not rfbc.isSetLowerFluxBound():
rfbc.setLowerFluxBound('lower')
if not rfbc.isSetUpperFluxBound():
rfbc.setUpperFluxBound('upper')
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 set_units(model, units):
""" Set units information on model.
:param model: Model
:param units: units info
"""
factory.create_objects(model, units)
def template_doc_bounds(model_id, create_min_max=True):
""" Create template bounds model.
Adds min and max functions
:param create_min_max:
:param model_id: model identifier
:return: SBMLDocument
"""
sbmlns = libsbml.SBMLNamespaces(SBML_LEVEL, SBML_VERSION, 'comp',
SBML_COMP_VERSION)
doc = libsbml.SBMLDocument(sbmlns)
doc.setPackageRequired(SBML_COMP_NAME, True)
model = doc.createModel()
model.setId("{}_bounds".format(model_id))
model.setName("{} (BOUNDS)".format(model_id))
model.setSBOTerm(comp.SBO_CONTINOUS_FRAMEWORK)
if create_min_max:
objects = [
# definition of min and max
Function('max', 'lambda(x,y, piecewise(x,gt(x,y),y) )',
name='min'),
Function('min', 'lambda(x,y, piecewise(x,lt(x,y),y) )',
name='max'),
]
factory.create_objects(model, objects)
return doc
def set_units(model, units):
""" Set units information on model.
:param model: Model
:param units: units info
"""
factory.create_objects(model, units)
def template_doc_bounds(model_id, create_min_max=True):
""" Create template bounds model.
Adds min and max functions
:param create_min_max:
:param model_id: model identifier
:return: SBMLDocument
"""
sbmlns = libsbml.SBMLNamespaces(SBML_LEVEL, SBML_VERSION, 'comp', SBML_COMP_VERSION)
doc = libsbml.SBMLDocument(sbmlns)
doc.setPackageRequired(SBML_COMP_NAME, True)
model = doc.createModel()
model.setId("{}_bounds".format(model_id))
model.setName("{} (BOUNDS)".format(model_id))
model.setSBOTerm(comp.SBO_CONTINOUS_FRAMEWORK)
if create_min_max:
objects = [
# definition of min and max
fac.Function('max', 'lambda(x,y, piecewise(x,gt(x,y),y) )', name='min'),
fac.Function('min', 'lambda(x,y, piecewise(x,lt(x,y),y) )', name='max'),
]
fac.create_objects(model, objects)
return doc
def create_dfba_species(model, model_fba, compartment_id, hasOnlySubstanceUnits=False, unit_amount=None, create_port=True,
exclude_sids=[]):
""" Add DFBA species and compartments from fba model to model.
Creates the dynamic species and respetive compartments with
the necessary ports.
This is used in the bounds submodel, update submodel and the
and top model.
:param model:
:param model_fba:
:return:
"""
objects = []
port_sids = []
ex_rids = utils.find_exchange_reactions(model_fba)
for ex_rid in ex_rids:
r = model_fba.getReaction(ex_rid)
sid = r.getReactant(0).getSpecies()
if sid in exclude_sids:
continue
s = model_fba.getSpecies(sid)
# exchange species to create
objects.append(
fac.Species(sid=sid, name=s.getName(), initialConcentration=1.0, substanceUnit=unit_amount,
hasOnlySubstanceUnits=hasOnlySubstanceUnits, compartment=compartment_id)
)
# port of exchange species
port_sids.append(sid)
fac.create_objects(model, objects)
if create_port:
comp.create_ports(model, idRefs=port_sids)
def create_dynamic_bounds(model_bounds, model_fba, unit_flux=None):
""" Creates the dynamic bounds for the model.
It is necessary to create copies of the fixed bounds from the fba model
which are subsequently used in the dynamic bounds calculation.
:return:
"""
fba_suffix = "_fba"
objects = []
ex_rids = utils.find_exchange_reactions(model_fba)
for ex_rid, sid in ex_rids.items():
r = model_fba.getReaction(ex_rid)
r_fbc = r.getPlugin(SBML_FBC_NAME)
# get compartment from species
s = model_bounds.getSpecies(sid)
cid = s.getCompartment()
# upper bound parameter (export from FBA, i.e increase concentration)
ub_id = r_fbc.getUpperFluxBound()
fba_ub_id = ub_id + fba_suffix
ub_value = model_fba.getParameter(ub_id).getValue()
ub_formula = "{}".format(fba_ub_id)
objects.extend([
Parameter(sid=fba_ub_id,
value=ub_value,
unit=unit_flux,
constant=True,
sboTerm=FLUX_BOUND_SBO),
AssignmentRule(sid=ub_id,
value=ub_formula,
name="fba export bound ({})".format(sid)),
])
# lower bound parameter (import to FBA, i.e decrease concentration)
lb_id = r_fbc.getLowerFluxBound()
fba_lb_id = lb_id + fba_suffix
lb_value = model_fba.getParameter(lb_id).getValue()
# concentration/amount formula for import depending on available species
if s.getHasOnlySubstanceUnits():
lb_formula = "max({}, -{}/dt)".format(fba_lb_id, sid)
else:
lb_formula = "max({}, -{}*{}/dt)".format(fba_lb_id, cid, sid)
objects.extend([
# default bounds from fba
Parameter(sid=fba_lb_id,
value=lb_value,
unit=unit_flux,
constant=False,
sboTerm=FLUX_BOUND_SBO),
# uptake bounds (lower bound)
AssignmentRule(sid=lb_id,
value=lb_formula,
name="dfba import bound ({})".format(sid)),
])
factory.create_objects(model_bounds, objects)
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 = [
Parameter(sid=lb_id,
value=lb_value,
unit=flux_unit,
constant=True,
sboTerm=FLUX_BOUND_SBO,
port=True),
Parameter(sid=ub_id,
value=ub_value,
unit=flux_unit,
constant=True,
sboTerm=FLUX_BOUND_SBO,
port=True),
]
factory.create_objects(model, parameters)
reactions = [
ExchangeReaction(species_id,
reversible=True,
lowerFluxBound=lb_id,
upperFluxBound=ub_id,
port=True)
]
ex_reactions = factory.create_objects(model, reactions)
# only one element in dictionary, get first value
return next(iter(ex_reactions.values()))
def bounds_model(sbml_file, directory, doc_fba=None):
""""
Submodel for dynamically calculating the flux bounds.
The dynamically changing flux bounds are the input to the
FBA model.
"""
doc = builder.template_doc_bounds(settings.MODEL_ID)
model = doc.getModel()
bounds_notes = notes.format("""
<h2>BOUNDS submodel</h2>
<p>Submodel for dynamically calculating the flux bounds.
The dynamically changing flux bounds are the input to the
FBA model.</p>
""")
utils.set_model_info(model, notes=bounds_notes, creators=creators, units=units, main_units=main_units)
# dt
compartment_id = "blood"
builder.create_dfba_dt(model, time_unit=UNIT_TIME, create_port=True)
# compartment
builder.create_dfba_compartment(model, compartment_id=compartment_id, unit_volume=UNIT_VOLUME, create_port=True)
# dynamic species
model_fba = doc_fba.getModel()
builder.create_dfba_species(model, model_fba, compartment_id=compartment_id, unit_amount=UNIT_AMOUNT,
create_port=True)
# bounds
builder.create_exchange_bounds(model, model_fba=model_fba, unit_flux=UNIT_FLUX, create_ports=True)
# bounds
fba_prefix = "fba"
model_fba = doc_fba.getModel()
objects = []
ex_rids = utils.find_exchange_reactions(model_fba)
for ex_rid, sid in ex_rids.items():
r = model_fba.getReaction(ex_rid)
# lower & upper bound parameters
r_fbc = r.getPlugin(builder.SBML_FBC_NAME)
lb_id = r_fbc.getLowerFluxBound()
fba_lb_id = fba_prefix + lb_id
lb_value = model_fba.getParameter(lb_id).getValue()
objects.extend([
# default bounds from fba
mc.Parameter(sid=fba_lb_id, value=lb_value, unit=UNIT_FLUX, constant=False),
# uptake bounds (lower bound)
mc.AssignmentRule(sid=lb_id, value="max({}, -{}*{}/dt)".format(fba_lb_id, compartment_id, sid)),
])
mc.create_objects(model, objects)
sbmlio.write_sbml(doc, filepath=pjoin(directory, sbml_file), validate=True)
def bounds_model(sbml_file, directory, doc_fba=None):
""""
Submodel for dynamically calculating the flux bounds.
The dynamically changing flux bounds are the input to the
FBA model.
"""
doc = builder.template_doc_bounds(settings.MODEL_ID)
model = doc.getModel()
bounds_notes = notes.format("""
<h2>BOUNDS submodel</h2>
<p>Submodel for dynamically calculating the flux bounds.
The dynamically changing flux bounds are the input to the
FBA model.</p>
""")
utils.set_model_info(model, notes=bounds_notes, creators=creators, units=units, main_units=main_units)
# dt
compartment_id = "blood"
builder.create_dfba_dt(model, time_unit=UNIT_TIME, create_port=True)
# compartment
builder.create_dfba_compartment(model, compartment_id=compartment_id, unit_volume=UNIT_VOLUME, create_port=True)
# dynamic species
model_fba = doc_fba.getModel()
builder.create_dfba_species(model, model_fba, compartment_id=compartment_id, unit_amount=UNIT_AMOUNT,
create_port=True)
# bounds
builder.create_exchange_bounds(model, model_fba=model_fba, unit_flux=UNIT_FLUX, create_ports=True)
# bounds
fba_prefix = "fba"
model_fba = doc_fba.getModel()
objects = []
ex_rids = utils.find_exchange_reactions(model_fba)
for ex_rid, sid in ex_rids.items():
r = model_fba.getReaction(ex_rid)
# lower & upper bound parameters
r_fbc = r.getPlugin(builder.SBML_FBC_NAME)
lb_id = r_fbc.getLowerFluxBound()
fba_lb_id = fba_prefix + lb_id
lb_value = model_fba.getParameter(lb_id).getValue()
objects.extend([
# default bounds from fba
mc.Parameter(sid=fba_lb_id, value=lb_value, unit=UNIT_FLUX, constant=False),
# uptake bounds (lower bound)
mc.AssignmentRule(sid=lb_id, value="max({}, -{}*{}/dt)".format(fba_lb_id, compartment_id, sid)),
])
mc.create_objects(model, objects)
sbmlio.write_sbml(doc, filepath=pjoin(directory, sbml_file), validate=True)
def bounds_model(sbml_file, directory, doc_fba, annotations=None):
""""
Bounds model.
"""
bounds_notes = notes.format("""
<h2>BOUNDS submodel</h2>
<p>Submodel for dynamically calculating the flux bounds.
The dynamically changing flux bounds are the input to the
FBA model.</p>
""")
doc = builder.template_doc_bounds(settings.MODEL_ID)
model = doc.getModel()
utils.set_model_info(model,
notes=bounds_notes,
creators=creators,
units=units, main_units=main_units)
builder.create_dfba_dt(model, step_size=DT_SIM, time_unit=UNIT_TIME, create_port=True)
# compartment
compartment_id = 'extern'
builder.create_dfba_compartment(model, compartment_id=compartment_id, unit_volume=UNIT_VOLUME,
create_port=True)
# species
model_fba = doc_fba.getModel()
builder.create_dfba_species(model, model_fba, compartment_id=compartment_id, unit_amount=UNIT_AMOUNT,
hasOnlySubstanceUnits=True, create_port=True)
# exchange bounds
builder.create_exchange_bounds(model, model_fba=model_fba, unit_flux=UNIT_FLUX, create_ports=True)
objects = [
# exchange bounds
# FIXME: readout the FBA network bounds
mc.Parameter(sid="lb_default", value=builder.LOWER_BOUND_DEFAULT, unit=UNIT_FLUX, constant=True),
# kinetic bound parameter & calculation
mc.Parameter(sid='ub_R1', value=1.0, unit=UNIT_FLUX, constant=False, sboTerm="SBO:0000625"),
mc.Parameter(sid='k1', value=-0.2, unit="per_s", name="k1", constant=False),
mc.RateRule(sid="ub_R1", value="k1*ub_R1"),
# bound assignment rules
mc.AssignmentRule(sid="lb_EX_A", value='max(lb_default, -A/dt)'),
mc.AssignmentRule(sid="lb_EX_C", value='max(lb_default, -C/dt)'),
]
mc.create_objects(model, objects)
# ports
comp.create_ports(model, portType=comp.PORT_TYPE_PORT,
idRefs=["ub_R1"])
if annotations:
annotation.annotate_sbml_doc(doc, annotations)
sbmlio.write_sbml(doc, filepath=os.path.join(directory, sbml_file), validate=True)
def bounds_model(sbml_file, directory, doc_fba, annotations=None):
""""
Bounds model.
"""
bounds_notes = notes.format("""
<h2>BOUNDS submodel</h2>
<p>Submodel for dynamically calculating the flux bounds.
The dynamically changing flux bounds are the input to the
FBA model.</p>
""")
doc = builder.template_doc_bounds(settings.MODEL_ID)
model = doc.getModel()
utils.set_model_info(model,
notes=bounds_notes,
creators=creators,
units=units, main_units=main_units)
builder.create_dfba_dt(model, step_size=DT_SIM, time_unit=UNIT_TIME, create_port=True)
# compartment
compartment_id = 'extern'
builder.create_dfba_compartment(model, compartment_id=compartment_id, unit_volume=UNIT_VOLUME,
create_port=True)
# species
model_fba = doc_fba.getModel()
builder.create_dfba_species(model, model_fba, compartment_id=compartment_id, unit_amount=UNIT_AMOUNT,
hasOnlySubstanceUnits=True, create_port=True)
# exchange bounds
builder.create_exchange_bounds(model, model_fba=model_fba, unit_flux=UNIT_FLUX, create_ports=True)
objects = [
# exchange bounds
# FIXME: readout the FBA network bounds
mc.Parameter(sid="lb_default", value=builder.LOWER_BOUND_DEFAULT, unit=UNIT_FLUX, constant=True),
# kinetic bound parameter & calculation
mc.Parameter(sid='ub_R1', value=1.0, unit=UNIT_FLUX, constant=False, sboTerm="SBO:0000625"),
mc.Parameter(sid='k1', value=-0.2, unit="per_s", name="k1", constant=False),
mc.RateRule(sid="ub_R1", value="k1*ub_R1"),
# bound assignment rules
mc.AssignmentRule(sid="lb_EX_A", value='max(lb_default, -A/dt)'),
mc.AssignmentRule(sid="lb_EX_C", value='max(lb_default, -C/dt)'),
]
mc.create_objects(model, objects)
# ports
comp.create_ports(model, portType=comp.PORT_TYPE_PORT,
idRefs=["ub_R1"])
if annotations:
annotator.annotate_sbml_doc(doc, annotations)
sbmlio.write_sbml(doc, filepath=os.path.join(directory, sbml_file), validate=True)
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 create_dfba_dt(model, step_size=DT_SIM, time_unit=None, create_port=True):
""" Creates the dt parameter in the model.
:param model:
:param create_port:
:param step_size:
:param time_unit:
:return:
"""
objects = [
fac.Parameter(sid=DT_ID, value=step_size, unit=time_unit, constant=True, sboTerm=DT_SBO)
]
fac.create_objects(model, objects)
if create_port:
comp.create_ports(model, idRefs=[DT_ID])
def bounds_model(sbml_file, directory, doc_fba=None):
""""
Submodel for dynamically calculating the flux bounds.
The dynamically changing flux bounds are the input to the
FBA model.
The units of the exchange fluxes must fit to the transported species.
"""
doc = builder.template_doc_bounds("ecoli")
model = doc.getModel()
bounds_notes = notes.format("""
<h2>BOUNDS submodel</h2>
<p>Submodel for dynamically calculating the flux bounds.
The dynamically changing flux bounds are the input to the
FBA model.</p>
""")
utils.set_model_info(model, notes=bounds_notes, creators=creators, units=units, main_units=main_units)
# dt
compartment_id = "bioreactor"
builder.create_dfba_dt(model, time_unit=UNIT_TIME, create_port=True)
# compartment
builder.create_dfba_compartment(model, compartment_id=compartment_id, unit_volume=UNIT_VOLUME, create_port=True)
# dynamic species
model_fba = doc_fba.getModel()
builder.create_dfba_species(model, model_fba, compartment_id=compartment_id, unit_amount=UNIT_AMOUNT, create_port=True,
exclude_sids=['X'])
# FIXME: define biomass separately, also port needed for biomass
mc.create_objects(model, [
mc.Parameter(sid='cf_X', value=1.0, unit="g_per_mmol", name="biomass conversion factor", constant=True),
mc.Species(sid='X', initialAmount=0.001, compartment=compartment_id, name='biomass', substanceUnit='g', hasOnlySubstanceUnits=True,
conversionFactor='cf_X')
])
# exchange & dynamic bounds
if not biomass_weighting:
builder.create_exchange_bounds(model, model_fba=model_fba, unit_flux=UNIT_FLUX, create_ports=True)
builder.create_dynamic_bounds(model, model_fba, unit_flux=UNIT_FLUX)
else:
builder.create_exchange_bounds(model, model_fba=model_fba, unit_flux=UNIT_FLUX_PER_G, create_ports=True)
builder.create_dynamic_bounds(model, model_fba, unit_flux=UNIT_FLUX_PER_G)
sbmlio.write_sbml(doc, filepath=pjoin(directory, sbml_file), validate=True)
def create_sbml(self, model):
from sbmlutils.factory import create_objects
# parameters and rules
create_objects(model, self.pars, key='parameters')
create_objects(model, self.rules, key='rules')
# reaction
r = model.createReaction() # type: libsbml.Reaction
r.setId(self.rid)
if self.name:
r.setName(self.name)
else:
r.setName(self.rid)
if self.compartment:
r.setCompartment(self.compartment)
if self.sboTerm:
r.setSBOTerm(self.sboTerm)
r.setReversible(self.equation.reversible)
r.setFast(self.fast)
# equation
for reactant in self.equation.reactants: # type: libsbml.SpeciesReference
sref = r.createReactant()
sref.setSpecies(reactant.sid)
sref.setStoichiometry(reactant.stoichiometry)
sref.setConstant(True)
for product in self.equation.products: # type: libsbml.SpeciesReference
sref = r.createProduct()
sref.setSpecies(product.sid)
sref.setStoichiometry(product.stoichiometry)
sref.setConstant(True)
for modifier in self.equation.modifiers:
sref = r.createModifier()
sref.setSpecies(modifier)
# kinetics
if self.formula:
ReactionTemplate.set_kinetic_law(model, r, self.formula.value)
# add fbc bounds
if self.upperFluxBound or self.lowerFluxBound:
r_fbc = r.getPlugin("fbc") # type: libsbml.FbcReactionPlugin
if self.upperFluxBound:
r_fbc.setUpperFluxBound(self.upperFluxBound)
if self.lowerFluxBound:
r_fbc.setLowerFluxBound(self.lowerFluxBound)
return r
def create_dummy_species(model, compartment_id, unit_amount=None, hasOnlySubstanceUnits=False):
""" Creates the dummy species in the top model.
Adds a deletion in the top model which removes the object again.
:param model: SBML model
:param compartment_id: compartment
:param unit_amount: unit
:param hasOnlySubstanceUnits: switch if amount or concentration
:return:
"""
# dummy species for dummy reactions (empty set)
fac.create_objects(model,
[fac.Species(sid=DUMMY_SPECIES_ID, name=DUMMY_SPECIES_ID, initialConcentration=0, substanceUnit=unit_amount,
hasOnlySubstanceUnits=hasOnlySubstanceUnits,
compartment=compartment_id, sboTerm=DUMMY_SPECIES_SBO),
])
def create_dynamic_bounds(model_bounds, model_fba, unit_flux=None):
""" Creates the dynamic bounds for the model.
It is necessary to create copies of the fixed bounds from the fba model
which are subsequently used in the dynamic bounds calculation.
:return:
"""
fba_suffix = "_fba"
objects = []
ex_rids = utils.find_exchange_reactions(model_fba)
for ex_rid, sid in ex_rids.items():
r = model_fba.getReaction(ex_rid)
r_fbc = r.getPlugin(SBML_FBC_NAME)
# get compartment from species
s = model_bounds.getSpecies(sid)
cid = s.getCompartment()
# upper bound parameter (export from FBA, i.e increase concentration)
ub_id = r_fbc.getUpperFluxBound()
fba_ub_id = ub_id + fba_suffix
ub_value = model_fba.getParameter(ub_id).getValue()
ub_formula = "{}".format(fba_ub_id)
objects.extend([
fac.Parameter(sid=fba_ub_id, value=ub_value, unit=unit_flux, constant=True, sboTerm=FLUX_BOUND_SBO),
fac.AssignmentRule(sid=ub_id, value=ub_formula, name="fba export bound ({})".format(sid)),
])
# lower bound parameter (import to FBA, i.e decrease concentration)
lb_id = r_fbc.getLowerFluxBound()
fba_lb_id = lb_id + fba_suffix
lb_value = model_fba.getParameter(lb_id).getValue()
# concentration/amount formula for import depending on available species
if s.getHasOnlySubstanceUnits():
lb_formula = "max({}, -{}/dt)".format(fba_lb_id, sid)
else:
lb_formula = "max({}, -{}*{}/dt)".format(fba_lb_id, cid, sid)
objects.extend([
# default bounds from fba
fac.Parameter(sid=fba_lb_id, value=lb_value, unit=unit_flux, constant=False, sboTerm=FLUX_BOUND_SBO),
# uptake bounds (lower bound)
fac.AssignmentRule(sid=lb_id, value=lb_formula, name="dfba import bound ({})".format(sid)),
])
fac.create_objects(model_bounds, objects)
def create_exchange_bounds(model_bounds,
model_fba,
unit_flux=None,
create_ports=True):
""" Creates the exchange reaction flux bounds in the bounds model.
:param model_bounds: the bounds model submodel
:param model_fba: the fba submodel
:param unit_flux: unit of fluxes
:param create_ports: should ports be created.
:return:
"""
ex_rids = utils.find_exchange_reactions(model_fba)
objects = []
port_sids = []
for ex_rid, sid in ex_rids.items():
r = model_fba.getReaction(ex_rid)
# lower & upper bound parameters
r_fbc = r.getPlugin(SBML_FBC_NAME)
lb_id = r_fbc.getLowerFluxBound()
lb_value = model_fba.getParameter(lb_id).getValue()
ub_id = r_fbc.getUpperFluxBound()
ub_value = model_fba.getParameter(ub_id).getValue()
# This creates the dynamical flux bound variables which are initialized with the
# constant fba bounds
objects.extend([
# for assignments
Parameter(sid=lb_id,
value=lb_value,
unit=unit_flux,
constant=False,
sboTerm=FLUX_BOUND_SBO),
Parameter(sid=ub_id,
value=ub_value,
unit=unit_flux,
constant=False,
sboTerm=FLUX_BOUND_SBO),
])
port_sids.extend([lb_id, ub_id])
# create bounds
factory.create_objects(model_bounds, objects)
# create ports
if create_ports:
comp.create_ports(model_bounds, idRefs=port_sids)
def test_event() -> None:
objects = [
Parameter(sid="p1", value=0.0, constant=False),
Event(sid="e1", trigger="time >= 10", assignments={"p1": 10.0}),
]
doc = libsbml.SBMLDocument(3, 1)
model = doc.createModel()
factory.create_objects(model, obj_iter=objects)
events = model.getListOfEvents()
assert len(events) == 1
e = model.getEvent("e1")
assert e is not None
assert e.getId() == "e1"
assignments = e.getListOfEventAssignments()
assert len(assignments) == 1
def test_event():
objects = [
fac.Parameter(sid="p1", value=0.0, constant=False),
fac.Event(sid="e1", trigger='time >= 10', assignments={'p1': 10.0})
]
doc = libsbml.SBMLDocument(3, 1)
model = doc.createModel()
fac.create_objects(model, obj_iter=objects)
events = model.getListOfEvents()
assert len(events) == 1
e = model.getEvent("e1")
assert e is not None
assert e.getId() == "e1"
assignments = e.getListOfEventAssignments()
assert len(assignments) == 1
def create_biomass_species(model, sid, unit, cf_unit, compartment_id, create_port=True):
""" Creates the biomass species.
:param model:
:return:
"""
# FIXME: implement
raise NotImplementedError
pass
fac.create_objects(model, [
fac.Parameter(sid='cf_X', value=1.0, unit="g_per_mmol", name="biomass conversion factor", constant=True),
fac.Species(sid='X', value=0.001, compartment='c', name='biomass', substanceUnit='g', hasOnlySubstanceUnits=True,
conversionFactor='cf_biomass')
])
if create_port:
comp.create_ports(model, idRefs=['X'])
def create_port_doc():
sbmlns = libsbml.SBMLNamespaces(3, 1, 'comp', 1)
doc = libsbml.SBMLDocument(sbmlns)
doc.setPackageRequired("comp", True)
model = doc.createModel()
model.setId("toy_update")
model.setName("toy (UPDATE submodel)")
model.setSBOTerm(comp.SBO_CONTINOUS_FRAMEWORK)
objects = [
fac.Compartment(sid='extern', value=1.0, unit="m3", constant=True, name='external compartment'),
fac.Species(sid='A', name="A", initialConcentration=10.0, hasOnlySubstanceUnits=True, compartment="extern"),
fac.Species(sid='C', name="C", initialConcentration=0, hasOnlySubstanceUnits=True, compartment="extern"),
fac.Parameter(sid="EX_A", value=1.0, constant=False, sboTerm="SBO:0000613"),
fac.Parameter(sid="EX_C", value=1.0, constant=False, sboTerm="SBO:0000613"),
]
fac.create_objects(model, obj_iter=objects)
return doc
def create_dfba_dt(model, step_size=DT_SIM, time_unit=None, create_port=True):
""" Creates the dt parameter in the model.
:param model:
:param create_port:
:param step_size:
:param time_unit:
:return:
"""
objects = [
Parameter(sid=DT_ID,
value=step_size,
unit=time_unit,
constant=True,
sboTerm=DT_SBO,
port=create_port)
]
factory.create_objects(model, objects)
def create_port_doc():
sbmlns = libsbml.SBMLNamespaces(3, 1, "comp", 1)
doc = libsbml.SBMLDocument(sbmlns)
doc.setPackageRequired("comp", True)
model = doc.createModel()
model.setId("toy_update")
model.setName("toy (UPDATE submodel)")
model.setSBOTerm(SBO_CONTINOUS_FRAMEWORK)
objects = [
fac.Compartment(
sid="extern",
value=1.0,
unit="m3",
constant=True,
name="external compartment",
),
fac.Species(
sid="A",
name="A",
initialConcentration=10.0,
hasOnlySubstanceUnits=True,
compartment="extern",
),
fac.Species(
sid="C",
name="C",
initialConcentration=0,
hasOnlySubstanceUnits=True,
compartment="extern",
),
fac.Parameter(sid="EX_A",
value=1.0,
constant=False,
sboTerm="SBO:0000613"),
fac.Parameter(sid="EX_C",
value=1.0,
constant=False,
sboTerm="SBO:0000613"),
]
fac.create_objects(model, obj_iter=objects)
return doc
def create_fba_doc():
sbmlns = libsbml.SBMLNamespaces(3, 1)
sbmlns.addPackageNamespace("fbc", 2)
sbmlns.addPackageNamespace("comp", 1)
doc = libsbml.SBMLDocument(sbmlns)
doc.setPackageRequired("comp", True)
doc.setPackageRequired("fbc", False)
model = doc.createModel()
mplugin = model.getPlugin("fbc")
mplugin.setStrict(True)
objects = [
fac.Compartment(sid='cell', value=1.0),
fac.Species(sid='A', initialConcentration=0, compartment="cell"),
fac.Species(sid='B', initialConcentration=0, compartment="cell"),
]
fac.create_objects(model, objects)
return doc
def test_event2():
objects = [
fac.Compartment('c', value=1.0),
fac.Species('S1', initialAmount=1.0, compartment='c'),
fac.Parameter(sid="p1", value=0.0, constant=False),
fac.Event(sid="e1", trigger='time >= 100', assignments={'p1': 10.0, 'S1': "p1 + 10"})
]
doc = libsbml.SBMLDocument(3, 1)
model = doc.createModel()
fac.create_objects(model, obj_iter=objects)
events = model.getListOfEvents()
assert len(events) == 1
e = model.getEvent("e1")
assert e is not None
assert e.getId() == "e1"
assignments = e.getListOfEventAssignments()
assert len(assignments) == 2
def create_fba_doc():
sbmlns = libsbml.SBMLNamespaces(3, 1)
sbmlns.addPackageNamespace("fbc", 2)
sbmlns.addPackageNamespace("comp", 1)
doc = libsbml.SBMLDocument(sbmlns)
doc.setPackageRequired("comp", True)
doc.setPackageRequired("fbc", False)
model = doc.createModel()
mplugin = model.getPlugin("fbc")
mplugin.setStrict(True)
objects = [
fac.Compartment(sid='cell', value=1.0),
fac.Species(sid='A', initialConcentration=0, compartment="cell"),
fac.Species(sid='B', initialConcentration=0, compartment="cell"),
]
fac.create_objects(model, objects)
return doc
def create_update_parameter(model, sid, unit_flux):
""" Creates the update parameter.
The update parameter correspond to the flux parameters
in the top model.
:param model:
:type model:
:param sid:
:type sid:
:param unit_flux:
:type unit_flux:
:return:
:rtype:
"""
pid = FLUX_PARAMETER_PREFIX + sid
parameter = fac.Parameter(sid=pid, value=1.0, constant=True, unit=unit_flux, sboTerm=UPDATE_PARAMETER_SBO)
fac.create_objects(model, [parameter])
# create port
comp.create_ports(model, portType=comp.PORT_TYPE_PORT,
idRefs=[pid])
return pid
def test_event2() -> None:
objects = [
Compartment("c", value=1.0),
Species("S1", initialAmount=1.0, compartment="c"),
Parameter(sid="p1", value=0.0, constant=False),
Event(
sid="e1", trigger="time >= 100", assignments={"p1": 10.0, "S1": "p1 + 10"}
),
]
doc = libsbml.SBMLDocument(3, 1)
model = doc.createModel()
factory.create_objects(model, obj_iter=objects)
events = model.getListOfEvents()
assert len(events) == 1
e = model.getEvent("e1")
assert e is not None
assert e.getId() == "e1"
assignments = e.getListOfEventAssignments()
assert len(assignments) == 2
def update_model(sbml_file, directory, doc_fba=None):
"""
Submodel for dynamically updating the metabolite count/concentration.
This updates the ode model based on the FBA fluxes.
"""
doc = builder.template_doc_update("ecoli")
model = doc.getModel()
update_notes = notes.format("""
<h2>UPDATE submodel</h2>
<p>Submodel for dynamically updating the metabolite count.
This updates the ode model based on the FBA fluxes.</p>
""")
utils.set_model_info(model, notes=update_notes, creators=creators, units=units, main_units=main_units)
# compartment
compartment_id = "bioreactor"
builder.create_dfba_compartment(model, compartment_id=compartment_id, unit_volume=UNIT_VOLUME, create_port=True)
# dynamic species
model_fba = doc_fba.getModel()
# creates all the exchange reactions, biomass must be handeled separately
builder.create_dfba_species(model, model_fba, compartment_id=compartment_id, unit_amount=UNIT_AMOUNT, create_port=True)
# FIXME: biomass via function
mc.create_objects(model, [
mc.Parameter(sid='cf_biomass', value=1.0, unit="g_per_mmol", name="biomass conversion factor", constant=True),
mc.Species(sid='X', initialAmount=0.001, compartment='c', name='biomass', substanceUnit='g', hasOnlySubstanceUnits=True,
conversionFactor='cf_biomass')
])
# update reactions
# FIXME: weight with X (biomass)
builder.create_update_reactions(model, model_fba=model_fba, formula="-{}", unit_flux=UNIT_FLUX,
modifiers=[])
# write SBML file
sbmlio.write_sbml(doc, filepath=pjoin(directory, sbml_file), validate=True)
def create_dfba_species(model,
model_fba,
compartment_id,
hasOnlySubstanceUnits=False,
unit_amount=None,
create_port=True,
exclude_sids=[]):
""" Add DFBA species and compartments from fba model to model.
Creates the dynamic species and respetive compartments with
the necessary ports.
This is used in the bounds submodel, update submodel and the
and top model.
:param model:
:param model_fba:
:return:
"""
objects = []
ex_rids = utils.find_exchange_reactions(model_fba)
for ex_rid in ex_rids:
r = model_fba.getReaction(ex_rid)
sid = r.getReactant(0).getSpecies()
if sid in exclude_sids:
continue
# exchange species
s = model_fba.getSpecies(sid)
objects.append(
Species(sid=sid,
name=s.getName(),
initialConcentration=1.0,
substanceUnit=unit_amount,
hasOnlySubstanceUnits=hasOnlySubstanceUnits,
compartment=compartment_id,
port=create_port))
factory.create_objects(model, objects)
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 = [
# flux parameter: flux from fba (rate of reaction)
Parameter(sid=pid_flux,
value=1.0,
constant=True,
unit=unit_flux,
sboTerm=FLUX_PARAMETER_SBO),
# dummy reaction (pseudoreaction)
Reaction(sid=rid_flux,
reversible=False,
equation=" -> {}".format(DUMMY_SPECIES_ID),
sboTerm=DUMMY_REACTION_SBO,
formula=('0 {}'.format(unit_flux), unit_flux)),
# flux assignment rule
AssignmentRule(pid_flux,
value=rid_flux,
sboTerm=FLUX_ASSIGNMENTRULE_SBO),
]
factory.create_objects(model, objects)
def create_exchange_bounds(model_bounds, model_fba, unit_flux=None, create_ports=True):
""" Creates the exchange reaction flux bounds in the bounds model.
:param model_bounds: the bounds model submodel
:param model_fba: the fba submodel
:param unit_flux: unit of fluxes
:param create_ports: should ports be created.
:return:
"""
ex_rids = utils.find_exchange_reactions(model_fba)
objects = []
port_sids = []
for ex_rid, sid in ex_rids.items():
r = model_fba.getReaction(ex_rid)
# lower & upper bound parameters
r_fbc = r.getPlugin(SBML_FBC_NAME)
lb_id = r_fbc.getLowerFluxBound()
lb_value = model_fba.getParameter(lb_id).getValue()
ub_id = r_fbc.getUpperFluxBound()
ub_value = model_fba.getParameter(ub_id).getValue()
# This creates the dynamical flux bound variables which are initialized with the
# constant fba bounds
objects.extend([
# for assignments
fac.Parameter(sid=lb_id, value=lb_value, unit=unit_flux, constant=False, sboTerm=FLUX_BOUND_SBO),
fac.Parameter(sid=ub_id, value=ub_value, unit=unit_flux, constant=False, sboTerm=FLUX_BOUND_SBO),
])
port_sids.extend([lb_id, ub_id])
# create bounds
fac.create_objects(model_bounds, objects)
# create ports
if create_ports:
comp.create_ports(model_bounds, idRefs=port_sids)
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)
factory.create_objects(model, [
Reaction(sid=rid_update,
sboTerm=UPDATE_REACTION_SBO,
equation="{} -> {}".format(sid, modifiers),
formula=(formula, None))
])
def create_dummy_species(model,
compartment_id,
unit_amount=None,
hasOnlySubstanceUnits=False):
""" Creates the dummy species in the top model.
Adds a deletion in the top model which removes the object again.
:param model: SBML model
:param compartment_id: compartment
:param unit_amount: unit
:param hasOnlySubstanceUnits: switch if amount or concentration
:return:
"""
# dummy species for dummy reactions (empty set)
objects = [
Species(sid=DUMMY_SPECIES_ID,
name=DUMMY_SPECIES_ID,
initialConcentration=0,
substanceUnit=unit_amount,
hasOnlySubstanceUnits=hasOnlySubstanceUnits,
compartment=compartment_id,
sboTerm=DUMMY_SPECIES_SBO),
]
factory.create_objects(model, objects)
def create_update_parameter(model, sid, unit_flux):
""" Creates the update parameter.
The update parameter correspond to the flux parameters
in the top model.
:param model:
:type model:
:param sid:
:type sid:
:param unit_flux:
:type unit_flux:
:return: id of parameter
:rtype:
"""
pid = FLUX_PARAMETER_PREFIX + sid
factory.create_objects(model, [
Parameter(sid=pid,
value=1.0,
constant=True,
unit=unit_flux,
sboTerm=UPDATE_PARAMETER_SBO,
port=True)
])
return pid
def create_dfba_compartment(model, compartment_id, unit_volume=None, create_port=True):
""" Creates the main compartment for the dynamic species.
:param model:
:param compartment_id: id
:param unit_volume: unit
:param create_port: flag to create port
:return: created libsbml.Compartment
"""
objects = [
fac.Compartment(sid=compartment_id, value=1.0, unit=unit_volume, constant=True, name=compartment_id,
spatialDimensions=3),
]
c = fac.create_objects(model, objects)
if create_port:
comp.create_ports(model, idRefs=[compartment_id])
return c
def create_dfba_compartment(model,
compartment_id,
unit_volume=None,
create_port=True):
""" Creates the main compartment for the dynamic species.
:param model:
:param compartment_id: id
:param unit_volume: unit
:param create_port: flag to create port
:return: created libsbml.Compartment
"""
objects = [
Compartment(sid=compartment_id,
value=1.0,
unit=unit_volume,
constant=True,
name=compartment_id,
spatialDimensions=3,
port=create_port),
]
sbml_objects = factory.create_objects(model, objects)
return next(iter(sbml_objects.values()))
def update_exchange_reactions(model, flux_unit):
""" Updates existing exchange reaction in FBA model.
Sets all the necessary information and checks that correct.
This is mainly used to prepare the exchange reactions of metabolites.
:param flux_unit:
:param model:
:return:
"""
# mapping of bounds to reactions
bounds_dict = dict()
ex_rids = utils.find_exchange_reactions(model)
for ex_rid in ex_rids:
r = model.getReaction(ex_rid)
# make reversible
if not r.getReversible():
r.setReversible(True)
logging.info("Exchange reaction set reversible: {}".format(r.getId()))
# fix ids for exchange reactions
sref = r.getReactant(0)
sid = sref.getSpecies()
rid = r.getId()
if rid != EXCHANGE_REACTION_PREFIX + sid:
r.setId(EXCHANGE_REACTION_PREFIX + sid)
logging.warning("Exchange reaction fixd id: {} -> {}".format(rid, EXCHANGE_REACTION_PREFIX + sid))
# new lookup necessary, due to possible changed ids
ex_rids = utils.find_exchange_reactions(model)
for ex_rid in ex_rids:
r = model.getReaction(ex_rid)
fbc_r = r.getPlugin(SBML_FBC_NAME)
# store bounds in dictionary for value lookup
for f_bound in ["getLowerFluxBound", "getUpperFluxBound"]:
bound_id = getattr(fbc_r, f_bound).__call__()
bound = model.getParameter(bound_id)
bounds_dict[bound_id] = bound.getValue()
# create unique bounds for exchange reactions
for ex_rid in ex_rids:
r = model.getReaction(ex_rid)
fbc_r = r.getPlugin(SBML_FBC_NAME)
lb_value = model.getParameter(fbc_r.getLowerFluxBound()).getValue()
ub_value = model.getParameter(fbc_r.getUpperFluxBound()).getValue()
lb_id = LOWER_BOUND_PREFIX + ex_rid
ub_id = UPPER_BOUND_PREFIX + ex_rid
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)
# set bounds
fbc.set_flux_bounds(r, lb=lb_id, ub=ub_id)
# create ports for bounds and reaction
comp.create_ports(model, portType=comp.PORT_TYPE_PORT,
idRefs=[ex_rid, lb_id, ub_id])
# check all the exchange reactions
for ex_rid in ex_rids:
check_exchange_reaction(model, ex_rid)
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 bounds_model(sbml_file, directory, doc_fba=None, annotations=None):
""""
Submodel for dynamically calculating the flux bounds.
The dynamically changing flux bounds are the input to the
FBA model.
"""
# TODO: the bounds model should be created based on the FBA model (i.e. use the exchange reactions
# to create the bounds info.
bounds_notes = notes.format("""
<h2>BOUNDS submodel</h2>
<p>Submodel for dynamically calculating the flux bounds.
The dynamically changing flux bounds are the input to the
FBA model.</p>
""")
doc = builder.template_doc_bounds(settings.MODEL_ID)
model = doc.getModel()
utils.set_model_info(model, notes=bounds_notes, creators=creators, units=units, main_units=main_units)
# dt
compartment_id = "bioreactor"
builder.create_dfba_dt(model, time_unit=UNIT_TIME, create_port=True)
# compartment
builder.create_dfba_compartment(model, compartment_id=compartment_id, unit_volume=UNIT_VOLUME, create_port=True)
# dynamic species
model_fba = doc_fba.getModel()
builder.create_dfba_species(model, model_fba, compartment_id=compartment_id, unit_amount=UNIT_AMOUNT,
create_port=True)
# bounds
builder.create_exchange_bounds(model, model_fba=model_fba, unit_flux=UNIT_FLUX, create_ports=True)
# bounds
fba_infix = "fba_"
model_fba = doc_fba.getModel()
objects = []
ex_rids = utils.find_exchange_reactions(model_fba)
for ex_rid, sid in ex_rids.items():
r = model_fba.getReaction(ex_rid)
# lower & upper bound parameters
r_fbc = r.getPlugin(builder.SBML_FBC_NAME)
lb_id = r_fbc.getLowerFluxBound()
fba_lb_id = builder.LOWER_BOUND_PREFIX + fba_infix + ex_rid
lb_value = model_fba.getParameter(lb_id).getValue()
objects.extend([
# default bounds from fba
mc.Parameter(sid=fba_lb_id, value=lb_value, unit=UNIT_FLUX, constant=False),
])
mc.create_objects(model, objects)
objects = [
# kinetic lower bounds
mc.Parameter(sid="lb_kin_EX_Glcxt", value=builder.LOWER_BOUND_DEFAULT, unit=UNIT_FLUX, constant=False,
sboTerm="SBO:0000612"),
mc.Parameter(sid="lb_kin_EX_O2", value=builder.LOWER_BOUND_DEFAULT, unit=UNIT_FLUX, constant=False,
sboTerm="SBO:0000612"),
# parameters for kinetic bounds
mc.Parameter(sid='Vmax_EX_O2', value=15, unit=UNIT_FLUX, constant=True),
mc.Parameter(sid='Vmax_EX_Glcxt', value=10, unit=UNIT_FLUX, constant=True),
mc.Parameter(sid='Km_EX_Glcxt', value=0.015, unit=UNIT_CONCENTRATION, name="Km_vGlcxt", constant=True),
# kinetic bounds (unintuitive direction due to the identical concentrations in bioreactor and model)
mc.AssignmentRule(sid="lb_kin_EX_Glcxt", value="-Vmax_EX_Glcxt * Glcxt/(Km_EX_Glcxt + Glcxt)"),
mc.AssignmentRule(sid="lb_kin_EX_O2", value="-Vmax_EX_O2"),
# exchange reaction bounds
# uptake bounds (lower bound)
# TODO: FIXME the X hack
# the bounds for the fba model have to be in mmol/h/gdw
mc.AssignmentRule(sid="lb_EX_Ac", value="max(lb_fba_EX_Ac, -Ac/X/1 l_per_mmol*bioreactor/dt)"),
mc.AssignmentRule(sid="lb_EX_X", value="max(lb_fba_EX_X, -X/X/1 l_per_mmol*bioreactor/dt)"),
mc.AssignmentRule(sid="lb_EX_Glcxt", value="max(lb_kin_EX_Glcxt, -Glcxt/X/1 l_per_mmol*bioreactor/dt)"),
mc.AssignmentRule(sid="lb_EX_O2", value="max(lb_kin_EX_O2, -O2/X/1 l_per_mmol*bioreactor/dt)"),
]
mc.create_objects(model, objects)
if annotations:
annotation.annotate_sbml_doc(doc, annotations)
sbmlio.write_sbml(doc, filepath=pjoin(directory, sbml_file), validate=True)
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 update_exchange_reactions(model, flux_unit):
""" Updates existing exchange reaction in FBA model.
Sets all the necessary information and checks that correct.
This is mainly used to prepare the exchange reactions of metabolites.
:param flux_unit:
:param model:
:return:
"""
# mapping of bounds to reactions
bounds_dict = dict()
ex_rids = utils.find_exchange_reactions(model)
for ex_rid in ex_rids:
r = model.getReaction(ex_rid)
# make reversible
if not r.getReversible():
r.setReversible(True)
logging.info("Exchange reaction set reversible: {}".format(
r.getId()))
# fix ids for exchange reactions
sref = r.getReactant(0)
sid = sref.getSpecies()
rid = r.getId()
if rid != EXCHANGE_REACTION_PREFIX + sid:
r.setId(EXCHANGE_REACTION_PREFIX + sid)
logging.warning("Exchange reaction fixd id: {} -> {}".format(
rid, EXCHANGE_REACTION_PREFIX + sid))
# new lookup necessary, due to possible changed ids
ex_rids = utils.find_exchange_reactions(model)
for ex_rid in ex_rids:
r = model.getReaction(ex_rid)
fbc_r = r.getPlugin(SBML_FBC_NAME)
# store bounds in dictionary for value lookup
for f_bound in ["getLowerFluxBound", "getUpperFluxBound"]:
bound_id = getattr(fbc_r, f_bound).__call__()
bound = model.getParameter(bound_id)
bounds_dict[bound_id] = bound.getValue()
# create unique bounds for exchange reactions
for ex_rid in ex_rids:
r = model.getReaction(ex_rid)
fbc_r = r.getPlugin(SBML_FBC_NAME)
lb_value = model.getParameter(fbc_r.getLowerFluxBound()).getValue()
ub_value = model.getParameter(fbc_r.getUpperFluxBound()).getValue()
lb_id = LOWER_BOUND_PREFIX + ex_rid
ub_id = UPPER_BOUND_PREFIX + ex_rid
parameters = [
Parameter(sid=lb_id,
value=lb_value,
unit=flux_unit,
constant=True,
sboTerm=FLUX_BOUND_SBO),
Parameter(sid=ub_id,
value=ub_value,
unit=flux_unit,
constant=True,
sboTerm=FLUX_BOUND_SBO),
]
factory.create_objects(model, parameters)
# set bounds
fbc.set_flux_bounds(r, lb=lb_id, ub=ub_id)
# create ports for bounds and reaction
comp.create_ports(model,
portType=comp.PORT_TYPE_PORT,
idRefs=[ex_rid, lb_id, ub_id])
# check all the exchange reactions
for ex_rid in ex_rids:
check_exchange_reaction(model, ex_rid)
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):
""" 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 fba_model(sbml_file, directory):
""" Create FBA submodel.
"""
# Read the model
fba_path = os.path.join(os.path.dirname(os.path.abspath(__file__)), 'data/ecoli_fba.xml')
doc_fba = sbmlio.read_sbml(fba_path)
# add comp
doc_fba.enablePackage("http://www.sbml.org/sbml/level3/version1/comp/version1", "comp", True)
doc_fba.setPackageRequired("comp", True)
# add notes
model = doc_fba.getModel()
fba_notes = notes.format("""DFBA FBA submodel.""")
utils.set_model_info(model, notes=fba_notes,
creators=None, units=units, main_units=main_units)
# clip R_ reaction and M_ metabolite prefixes
utils.clip_prefixes_in_model(model)
# set id & framework
model.setId('ecoli_fba')
model.setName('ecoli (FBA)')
model.setSBOTerm(comp.SBO_FLUX_BALANCE_FRAMEWORK)
# add units and information
for species in model.getListOfSpecies():
species.setInitialConcentration(0.0)
species.setHasOnlySubstanceUnits(False)
species.setUnits(UNIT_AMOUNT)
for compartment in model.getListOfCompartments():
compartment.setUnits(UNIT_VOLUME)
# The ATPM (atp maintainance reactions creates many problems in the DFBA)
# mainly resulting in infeasible solutions when some metabolites run out.
# ATP -> ADP is part of the biomass, so we set the lower bound to zero
r_ATPM = model.getReaction('ATPM')
r_ATPM_fbc = r_ATPM.getPlugin(builder.SBML_FBC_NAME)
lb_id = r_ATPM_fbc.getLowerFluxBound()
model.getParameter(lb_id).setValue(0.0) # 8.39 before
# make unique upper and lower bounds for exchange reaction
if not biomass_weighting:
builder.update_exchange_reactions(model=model, flux_unit=UNIT_FLUX)
else:
builder.update_exchange_reactions(model=model, flux_unit=UNIT_FLUX_PER_G)
# add exchange reaction for biomass (X)
# we are adding the biomass component to the biomass function and create an
# exchange reaction for it
r_biomass = model.getReaction('BIOMASS_Ecoli_core_w_GAM')
# FIXME: refactor in function
# FIXME: annotate biomass species (SBO for biomass missing)
mc.create_objects(model, [
mc.Parameter(sid='cf_X', value=1.0, unit="g_per_mmol", name="biomass conversion factor", constant=True),
mc.Species(sid='X', initialAmount=0.001, compartment='c', name='biomass', substanceUnit='g', hasOnlySubstanceUnits=True,
conversionFactor='cf_X')
])
pr_biomass = r_biomass.createProduct()
pr_biomass.setSpecies('X')
pr_biomass.setStoichiometry(1.0)
pr_biomass.setConstant(True)
# FIXME: the flux units must fit to the species units.
if not biomass_weighting:
builder.create_exchange_reaction(model, species_id='X', flux_unit=UNIT_FLUX, exchange_type=builder.EXCHANGE_EXPORT)
else:
builder.create_exchange_reaction(model, species_id='X', flux_unit=UNIT_FLUX_PER_G, exchange_type=builder.EXCHANGE_EXPORT)
# write SBML file
sbmlio.write_sbml(doc_fba, filepath=pjoin(directory, sbml_file), validate=True)
# Set kinetic laws to zero for kinetic simulation
'''
for reaction in model.getListOfReactions():
ast_node = mc.ast_node_from_formula(model=model, formula='0 {}'.format(UNIT_FLUX))
law = reaction.createKineticLaw()
law.setMath(ast_node)
'''
return doc_fba
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
# Parameter(sid="Y", name="biomass [g_per_l]", value=1.0, unit="g_per_l"),
# oxygen exchange parameters
Parameter(sid="O2_ref",
name="O2 reference",
value=0.21,
unit=UNIT_CONCENTRATION),
Parameter(sid="kLa", name="O2 mass transfer", value=7.5, unit='per_h'),
]
factory.create_objects(model, objects)
# oxygen transfer reaction
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:
annotator.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 xpp2sbml(
xpp_file: Path,
sbml_file: Path,
force_lower: bool = False,
validate: bool = True,
debug: bool = False,
):
"""Reads given xpp_file and converts to SBML file.
:param xpp_file: xpp input ode file
:param sbml_file: sbml output file
:param force_lower: force lower case for all lines
:param validate: perform validation on the generated SBML file
:return:
"""
print("-" * 80)
print("xpp2sbml: ", xpp_file, "->", sbml_file)
print("-" * 80)
doc = libsbml.SBMLDocument(3, 1)
model = doc.createModel()
parameters = []
initial_assignments = []
rate_rules = []
assignment_rules = []
functions = [
# definition of min and max
fac.Function("max",
"lambda(x,y, piecewise(x,gt(x,y),y) )",
name="minimum"),
fac.Function("min",
"lambda(x,y, piecewise(x,lt(x,y),y) )",
name="maximum"),
# heav (heavyside)
fac.Function(
"heav",
"lambda(x, piecewise(0,lt(x,0), 0.5, eq(x, 0), 1,gt(x,0), 0))",
name="heavyside",
),
# mod (modulo)
fac.Function("mod", "lambda(x,y, x % y)", name="modulo"),
]
function_definitions = []
events = []
def replace_fdef():
""" Replace all arguments within the formula definitions."""
changes = False
for k, fdata in enumerate(function_definitions):
for i in range(len(function_definitions)):
if i != k:
# replace i with k
formula = function_definitions[i]["formula"]
new_formula = xpp_helpers.replace_formula(
formula,
fid=function_definitions[k]["fid"],
old_args=function_definitions[k]["old_args"],
new_args=function_definitions[k]["new_args"],
)
if new_formula != formula:
function_definitions[i]["formula"] = new_formula
function_definitions[i]["new_args"] = list(
sorted(
set(function_definitions[i]["new_args"] +
function_definitions[k]["new_args"])))
changes = True
return changes
def create_initial_assignment(sid, value):
""" Helper for creating initial assignments """
# check if valid identifier
if "(" in sid:
warnings.warn(
"sid is not valid: {}. Initial assignment is not generated".
format(sid))
return
try:
f_value = float(value)
parameters.append(
fac.Parameter(
sid=sid,
value=f_value,
name="{} = {}".format(sid, value),
constant=False,
))
except ValueError:
"""
Initial data are optional, XPP sets them to zero by default (many xpp model don't write the p(0)=0.
"""
parameters.append(
fac.Parameter(sid=sid, value=0.0, name=sid, constant=False))
initial_assignments.append(
fac.InitialAssignment(sid=sid,
value=value,
name="{} = {}".format(sid, value)))
###########################################################################
# First iteration to parse relevant lines and get the replacement patterns
###########################################################################
parsed_lines = []
# with open(xpp_file, encoding="utf-8") as f:
with open(xpp_file) as f:
lines = f.readlines()
# add info to sbml
text = escape_string("".join(lines))
fac.set_notes(model, NOTES.format(text))
old_line = None
for line in lines:
if force_lower:
line = line.lower()
# clean up the ends
line = line.rstrip("\n").strip()
# handle douple continuation characters in some models
line = line.replace("\\\\", "\\")
# handle semicolons
line = line.rstrip(";")
# join continuation
if old_line:
line = old_line + line
old_line = None
# empty line
if len(line) == 0:
continue
# comment line
if line[0] in XPP_COMMENT_CHARS:
continue
# xpp setting
if line.startswith(XPP_SETTING_CHAR):
continue
# end word
if line == XPP_END_WORD:
continue
# line continuation
if line.endswith(XPP_CONTINUATION_CHAR):
old_line = line.rstrip(XPP_CONTINUATION_CHAR)
continue
# handle the power function
line = line.replace("**", "^")
# handle if(...)then(...)else()
pattern_ite = re.compile(
r"if\s*\((.*)\)\s*then\s*\((.*)\)\s*else\s*\((.*)\)")
pattern_ite_sub = re.compile(
r"if\s*\(.*\)\s*then\s*\(.*\)\s*else\s*\(.*\)")
groups = re.findall(pattern_ite, line)
for group in groups:
condition = group[0]
assignment = group[1]
otherwise = group[2]
f_piecewise = "piecewise({}, {}, {})".format(
assignment, condition, otherwise)
line = re.sub(pattern_ite_sub, f_piecewise, line)
################################
# Function definitions
################################
""" Functions are defined in xpp via fid(arguments) = formula
f(x,y) = x^2/(x^2+y^2)
They can have up to 9 arguments.
The difference to SBML functions is that xpp functions have access to the global parameter values
"""
f_pattern = re.compile(r"(.*)\s*\((.*)\)\s*=\s*(.*)")
groups = re.findall(f_pattern, line)
if groups:
# function definitions found
fid, args, formula = groups[0]
# handles the initial assignments which look like function definitions
if args == "0":
parsed_lines.append(line)
continue
# necessary to find the additional arguments from the ast_node
ast = libsbml.parseL3Formula(formula)
names = set(xpp_helpers.find_names_in_ast(ast))
old_args = [t.strip() for t in args.split(",")]
new_args = [a for a in names if a not in old_args]
# handle special functions
if fid == "power":
warnings.warn(
"power function cannot be added to model, rename function."
)
else:
# store functions with additional arguments
function_definitions.append({
"fid": fid,
"old_args": old_args,
"new_args": new_args,
"formula": formula,
})
# don't append line, function definition has been handeled
continue
parsed_lines.append(line)
if debug:
print("\n\nFUNCTION_DEFINITIONS")
pprint(function_definitions)
# functions can use functions so this also must be replaced
changes = True
while changes:
changes = replace_fdef()
# clean the new arguments
for fdata in function_definitions:
fdata["new_args"] = list(sorted(set(fdata["new_args"])))
if debug:
print("\nREPLACED FUNCTION_DEFINITIONS")
pprint(function_definitions)
# Create function definitions
for k, fdata in enumerate(function_definitions):
fid = fdata["fid"]
formula = fdata["formula"]
arguments = ",".join(fdata["old_args"] + fdata["new_args"])
functions.append(
fac.Function(fid, "lambda({}, {})".format(arguments, formula)), )
###########################################################################
# Second iteration
###########################################################################
if debug:
print("\nPARSED LINES")
pprint(parsed_lines)
print("\n\n")
for line in parsed_lines:
# replace function definitions in lines
new_line = line
for fdata in function_definitions:
new_line = xpp_helpers.replace_formula(new_line, fdata["fid"],
fdata["old_args"],
fdata["new_args"])
if new_line != line:
if False:
print("\nReplaced FD", fdata["fid"], ":", new_line)
print("->", new_line, "\n")
line = new_line
if debug:
# line after function replacements
print("*" * 3, line, "*" * 3)
################################
# Start parsing the given line
################################
# check for the equal sign
tokens = line.split("=")
tokens = [t.strip() for t in tokens]
#######################
# Line without '=' sign
#######################
# wiener
if len(tokens) == 1:
items = [t.strip() for t in tokens[0].split(" ") if len(t) > 0]
# keyword, value
if len(items) == 2:
xid, sid = items[0], items[1]
xpp_type = parse_keyword(xid)
# wiener
if xpp_type == XPP_WIE:
"""Wiener parameters are normally distributed numbers with zero mean
and unit standard deviation. They are useful in stochastic simulations since
they automatically scale with change in the integration time step.
Their names are listed separated by commas or spaces."""
# FIXME: this should be encoded using dist
parameters.append(fac.Parameter(sid=sid, value=0.0))
continue # line finished
else:
warnings.warn("XPP line not parsed: '{}'".format(line))
#####################
# Line with '=' sign
#####################
# parameter, aux, ode, initial assignments
elif len(tokens) >= 2:
left = tokens[0]
items = [t.strip() for t in left.split(" ") if len(t) > 0]
# keyword based information, i.e 2 items are on the left of the first '=' sign
if len(items) == 2:
xid = items[0] # xpp keyword
xpp_type = parse_keyword(xid)
expression = (" ".join(items[1:]) + "=" + "=".join(tokens[1:])
) # full expression after keyword
parts = parts_from_expression(expression)
if False:
print("xid:", xid)
print("expression:", expression)
print("parts:", parts)
# parameter & numbers
if xpp_type in [XPP_PAR, XPP_NUM]:
"""Parameter values are optional; if not they are set to zero.
Number declarations are like parameter declarations, except that they cannot be
changed within the program and do not appear in the parameter window."""
for part in parts:
sid, value = sid_value_from_part(part)
create_initial_assignment(sid, value)
# aux
elif xpp_type == XPP_AUX:
"""Auxiliary quantities are expressions that depend on all of your dynamic
variables which you want to keep track of. Energy is one such example. They are declared
like fixed quantities, but are prefaced by aux ."""
for part in parts:
sid, value = sid_value_from_part(part)
if sid == value:
# avoid circular dependencies (no information in statement)
pass
else:
assignment_rules.append(
fac.AssignmentRule(sid=sid, value=value))
# init
elif xpp_type == XPP_INIT:
for part in parts:
sid, value = sid_value_from_part(part)
create_initial_assignment(sid, value)
# table
elif xpp_type == XPP_TAB:
"""The Table declaration allows the user to specify a function of 1 variable in terms
of a lookup table which uses linear interpolation. The name of the function follows the
declaration and this is followed by (i) a filename (ii) or a function of "t"."""
warnings.warn(
"XPP_TAB not supported: XPP line not parsed: '{}'".
format(line))
else:
warnings.warn("XPP line not parsed: '{}'".format(line))
elif len(items) >= 2:
xid = items[0]
xpp_type = parse_keyword(xid)
# global
if xpp_type == XPP_GLO:
"""Global flags are expressions that signal events when they change sign, from less than
to greater than zero if sign=1 , greater than to less than if sign=-1 or either way
if sign=0. The condition should be delimited by braces {} The events are of the form
variable=expression, are delimited by braces, and separated by semicolons. When the
condition occurs all the variables in the event set are changed possibly discontinuously.
"""
# global sign {condition} {name1 = form1; ...}
pattern_global = re.compile(
r"([+,-]{0,1}\d{1})\s+\{{0,1}(.*)\{{0,1}\s+\{(.*)\}")
groups = re.findall(pattern_global, line)
if groups:
g = groups[0]
sign = int(g[0])
trigger = g[1]
# FIXME: handle sign=-1, sign=0, sign=+1
if sign == -1:
trigger = g[1] + ">= 0"
elif sign == 1:
trigger = g[1] + ">= 0"
elif sign == 0:
trigger = g[1] + ">= 0"
assignment_parts = [t.strip() for t in g[2].split(";")]
assignments = {}
for p in assignment_parts:
key, value = p.split("=")
assignments[key] = value
events.append(
fac.Event(
sid="e{}".format(len(events)),
trigger=trigger,
assignments=assignments,
))
else:
warnings.warn(
"global expression could not be parsed: {}".format(
line))
else:
warnings.warn("XPP line not parsed: '{}'".format(line))
# direct assignments
elif len(items) == 1:
right = tokens[1]
# init
if left.endswith("(0)"):
sid, value = left[0:-3], right
create_initial_assignment(sid, value)
# difference equations
elif left.endswith("(t+1)"):
warnings.warn(
"Difference Equations not supported: XPP line not parsed: '{}'"
.format(line))
# ode
elif left.endswith("'"):
sid = left[0:-1]
rate_rules.append(fac.RateRule(sid=sid, value=right))
elif left.endswith("/dt"):
sid = left[1:-3]
rate_rules.append(fac.RateRule(sid=sid, value=right))
# assignment rules
else:
assignment_rules.append(
fac.AssignmentRule(sid=left, value=right))
else:
warnings.warn("XPP line not parsed: '{}'".format(line))
# add time
assignment_rules.append(
fac.AssignmentRule(sid="t", value="time", name="model time"))
# create SBML objects
objects = (parameters + initial_assignments + functions + rate_rules +
assignment_rules + events)
fac.create_objects(model, obj_iter=objects, debug=False)
"""
Parameter values are optional; if not they are set to zero in xpp.
Many models do not encode the initial zeros.
"""
for p in doc.getModel().getListOfParameters():
if not p.isSetValue():
p.setValue(0.0)
sbml.write_sbml(
doc,
sbml_file,
validate=validate,
program_name="sbmlutils",
program_version=__version__,
units_consistency=False,
)
def create_sbml(self, sbml_level=SBML_LEVEL, sbml_version=SBML_VERSION):
""" Create the SBML model
:return:
:rtype:
"""
from sbmlutils.validation import check
logging.info('*'*40)
logging.info(self.model_id)
logging.info('*' * 40)
# create core model
sbmlns = libsbml.SBMLNamespaces(sbml_level, sbml_version)
# add all the packages
# FIXME: only add packages which are required for the model
sbmlns.addPackageNamespace("fbc", 2)
sbmlns.addPackageNamespace("comp", 1)
# sbmlns.addPackageNamespace("distrib", 1)
self.doc = libsbml.SBMLDocument(sbmlns)
self.doc.setPackageRequired("comp", True)
self.doc.setPackageRequired("fbc", False)
# self.doc.setPackageRequired("distrib", True)
self.model = self.doc.createModel()
fbc_plugin = self.model.getPlugin("fbc")
fbc_plugin.setStrict(False)
# name & id
check(self.model.setId(self.model_id), 'set id')
check(self.model.setName(self.model_id), 'set name')
# notes
if hasattr(self, 'notes') and self.notes is not None:
factory.set_notes(self.model, self.notes)
# history
if hasattr(self, 'creators'):
history.set_model_history(self.model, self.creators)
# model units
if hasattr(self, 'model_units'):
factory.set_model_units(self.model, self.model_units)
# lists ofs
for attr in [
'externalModelDefinitions',
'submodels',
'units',
'functions',
'parameters',
'compartments',
'species',
'assignments',
'rules',
'rate_rules',
'reactions',
'events',
'constraints',
'ports',
'replacedElements',
'deletions',
'objectives',
'layouts'
]:
# create the respective objects
if hasattr(self, attr):
objects = getattr(self, attr)
if objects:
factory.create_objects(self.model, obj_iter=objects, key=attr)
else:
logging.warning("Not defined: <{}> ".format(attr))
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 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 bounds_model(sbml_file, directory, doc_fba=None, annotations=None):
""""
Submodel for dynamically calculating the flux bounds.
The dynamically changing flux bounds are the input to the
FBA model.
"""
# TODO: the bounds model should be created based on the FBA model (i.e. use the exchange reactions
# to create the bounds info.
bounds_notes = notes.format("""
<h2>BOUNDS submodel</h2>
<p>Submodel for dynamically calculating the flux bounds.
The dynamically changing flux bounds are the input to the
FBA model.</p>
""")
doc = builder.template_doc_bounds(settings.MODEL_ID)
model = doc.getModel()
utils.set_model_info(model,
notes=bounds_notes,
creators=creators,
units=units,
main_units=main_units)
# dt
compartment_id = "bioreactor"
builder.create_dfba_dt(model, time_unit=UNIT_TIME, create_port=True)
# compartment
builder.create_dfba_compartment(model,
compartment_id=compartment_id,
unit_volume=UNIT_VOLUME,
create_port=True)
# dynamic species
model_fba = doc_fba.getModel()
builder.create_dfba_species(model,
model_fba,
compartment_id=compartment_id,
unit_amount=UNIT_AMOUNT,
create_port=True)
# bounds
builder.create_exchange_bounds(model,
model_fba=model_fba,
unit_flux=UNIT_FLUX,
create_ports=True)
# bounds
fba_infix = "fba_"
model_fba = doc_fba.getModel()
objects = []
ex_rids = utils.find_exchange_reactions(model_fba)
for ex_rid, sid in ex_rids.items():
r = model_fba.getReaction(ex_rid)
# lower & upper bound parameters
r_fbc = r.getPlugin(builder.SBML_FBC_NAME)
lb_id = r_fbc.getLowerFluxBound()
fba_lb_id = builder.LOWER_BOUND_PREFIX + fba_infix + ex_rid
lb_value = model_fba.getParameter(lb_id).getValue()
objects.extend([
# default bounds from fba
Parameter(sid=fba_lb_id,
value=lb_value,
unit=UNIT_FLUX,
constant=False),
])
factory.create_objects(model, objects)
objects = [
# kinetic lower bounds
Parameter(sid="lb_kin_EX_Glcxt",
value=builder.LOWER_BOUND_DEFAULT,
unit=UNIT_FLUX,
constant=False,
sboTerm="SBO:0000612"),
Parameter(sid="lb_kin_EX_O2",
value=builder.LOWER_BOUND_DEFAULT,
unit=UNIT_FLUX,
constant=False,
sboTerm="SBO:0000612"),
# parameters for kinetic bounds
Parameter(sid='Vmax_EX_O2', value=15, unit=UNIT_FLUX, constant=True),
Parameter(sid='Vmax_EX_Glcxt', value=10, unit=UNIT_FLUX,
constant=True),
Parameter(sid='Km_EX_Glcxt',
value=0.015,
unit=UNIT_CONCENTRATION,
name="Km_vGlcxt",
constant=True),
# kinetic bounds (unintuitive direction due to the identical concentrations in bioreactor and model)
AssignmentRule(sid="lb_kin_EX_Glcxt",
value="-Vmax_EX_Glcxt * Glcxt/(Km_EX_Glcxt + Glcxt)"),
AssignmentRule(sid="lb_kin_EX_O2", value="-Vmax_EX_O2"),
# exchange reaction bounds
# uptake bounds (lower bound)
# TODO: FIXME the X hack
# the bounds for the fba model have to be in mmol/h/gdw
AssignmentRule(
sid="lb_EX_Ac",
value="max(lb_fba_EX_Ac, -Ac/X/1 l_per_mmol*bioreactor/dt)"),
AssignmentRule(
sid="lb_EX_X",
value="max(lb_fba_EX_X, -X/X/1 l_per_mmol*bioreactor/dt)"),
AssignmentRule(
sid="lb_EX_Glcxt",
value="max(lb_kin_EX_Glcxt, -Glcxt/X/1 l_per_mmol*bioreactor/dt)"),
AssignmentRule(
sid="lb_EX_O2",
value="max(lb_kin_EX_O2, -O2/X/1 l_per_mmol*bioreactor/dt)"),
]
factory.create_objects(model, objects)
if annotations:
annotator.annotate_sbml_doc(doc, annotations)
sbmlio.write_sbml(doc, filepath=pjoin(directory, sbml_file), validate=True)
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
def fba_model(sbml_file, directory):
""" Create FBA submodel.
"""
# Read the model
fba_path = os.path.join(os.path.dirname(os.path.abspath(__file__)),
'data/ecoli_fba.xml')
doc_fba = sbml.read_sbml(fba_path)
# add comp
doc_fba.enablePackage(
"http://www.sbml.org/sbml/level3/version1/comp/version1", "comp", True)
doc_fba.setPackageRequired("comp", True)
# add notes
model = doc_fba.getModel()
fba_notes = notes.format("""DFBA FBA submodel.""")
utils.set_model_info(model,
notes=fba_notes,
creators=None,
units=units,
main_units=main_units)
# clip R_ reaction and M_ metabolite prefixes
utils.clip_prefixes_in_model(model)
# set id & framework
model.setId('ecoli_fba')
model.setName('ecoli (FBA)')
model.setSBOTerm(comp.SBO_FLUX_BALANCE_FRAMEWORK)
# add units and information
for species in model.getListOfSpecies():
species.setInitialConcentration(0.0)
species.setHasOnlySubstanceUnits(False)
species.setUnits(UNIT_AMOUNT)
for compartment in model.getListOfCompartments():
compartment.setUnits(UNIT_VOLUME)
# The ATPM (atp maintainance reactions creates many problems in the DFBA)
# mainly resulting in infeasible solutions when some metabolites run out.
# ATP -> ADP is part of the biomass, so we set the lower bound to zero
r_ATPM = model.getReaction('ATPM')
r_ATPM_fbc = r_ATPM.getPlugin(builder.SBML_FBC_NAME)
lb_id = r_ATPM_fbc.getLowerFluxBound()
model.getParameter(lb_id).setValue(0.0) # 8.39 before
# make unique upper and lower bounds for exchange reaction
if not biomass_weighting:
builder.update_exchange_reactions(model=model, flux_unit=UNIT_FLUX)
else:
builder.update_exchange_reactions(model=model,
flux_unit=UNIT_FLUX_PER_G)
# add exchange reaction for biomass (X)
# we are adding the biomass component to the biomass function and create an
# exchange reaction for it
r_biomass = model.getReaction('BIOMASS_Ecoli_core_w_GAM')
# FIXME: refactor in function
# FIXME: annotate biomass species (SBO for biomass missing)
mc.create_objects(model, [
mc.Parameter(sid='cf_X',
value=1.0,
unit="g_per_mmol",
name="biomass conversion factor",
constant=True),
mc.Species(sid='X',
initialAmount=0.001,
compartment='c',
name='biomass',
substanceUnit='g',
hasOnlySubstanceUnits=True,
conversionFactor='cf_X')
])
pr_biomass = r_biomass.createProduct()
pr_biomass.setSpecies('X')
pr_biomass.setStoichiometry(1.0)
pr_biomass.setConstant(True)
# FIXME: the flux units must fit to the species units.
if not biomass_weighting:
builder.create_exchange_reaction(model,
species_id='X',
flux_unit=UNIT_FLUX,
exchange_type=builder.EXCHANGE_EXPORT)
else:
builder.create_exchange_reaction(model,
species_id='X',
flux_unit=UNIT_FLUX_PER_G,
exchange_type=builder.EXCHANGE_EXPORT)
# write SBML file
sbml.write_sbml(doc_fba,
filepath=pjoin(directory, sbml_file),
validate=True)
# Set kinetic laws to zero for kinetic simulation
'''
for reaction in model.getListOfReactions():
ast_node = mc.ast_node_from_formula(model=model, formula='0 {}'.format(UNIT_FLUX))
law = reaction.createKineticLaw()
law.setMath(ast_node)
'''
return doc_fba
