def update_model(sbml_file, directory, doc_fba=None, annotations=None):
""" Update model.
"""
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>
""")
doc = builder.template_doc_update(settings.MODEL_ID)
model = doc.getModel()
utils.set_model_info(model,
notes=update_notes,
creators=creators,
units=units, main_units=main_units)
# compartment
compartment_id = "extern"
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,
hasOnlySubstanceUnits=True, create_port=True)
# update reactions
builder.create_update_reactions(model, model_fba=model_fba, formula="-{}", unit_flux=UNIT_FLUX,
modifiers=[])
# write SBML file
if annotations:
annotator.annotate_sbml_doc(doc, annotations)
sbmlio.write_sbml(doc, filepath=os.path.join(directory, sbml_file), validate=True)
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(settings.MODEL_ID)
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 = "blood"
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)
# 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 update_model(sbml_file, directory, doc_fba=None, annotations=None):
""" Update model.
"""
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>
""")
doc = builder.template_doc_update(settings.MODEL_ID)
model = doc.getModel()
utils.set_model_info(model,
notes=update_notes,
creators=creators,
units=units, main_units=main_units)
# compartment
compartment_id = "extern"
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,
hasOnlySubstanceUnits=True, create_port=True)
# update reactions
builder.create_update_reactions(model, model_fba=model_fba, formula="-{}", unit_flux=UNIT_FLUX,
modifiers=[])
# write SBML file
if annotations:
annotation.annotate_sbml_doc(doc, annotations)
sbmlio.write_sbml(doc, filepath=os.path.join(directory, sbml_file), validate=True)
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(settings.MODEL_ID)
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 = "blood"
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)
# 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 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 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 = 'cell'
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=False,
create_port=True)
# exchange bounds
builder.create_exchange_bounds(model_bounds=model,
model_fba=model_fba,
unit_flux=UNIT_FLUX,
create_ports=True)
builder.create_dynamic_bounds(model_bounds=model,
model_fba=model_fba,
unit_flux=UNIT_FLUX)
# annotations
if annotations:
annotator.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=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 top_model(sbml_file, directory, emds, doc_fba=None, validate=True):
""" Create 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>
""")
# 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 = "blood"
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)
# write SBML file
sbmlio.write_sbml(doc, filepath=os.path.join(directory, sbml_file), validate=validate)
# change back into working dir
os.chdir(working_dir)
def top_model(sbml_file, directory, emds, doc_fba=None, validate=True):
""" Create 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>
""")
# 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 = "blood"
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_CONCENTRATION,
create_port=False)
# dummy species
builder.create_dummy_species(model, compartment_id=compartment_id, unit_amount=UNIT_CONCENTRATION)
# 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)
# write SBML file
sbmlio.write_sbml(doc, filepath=os.path.join(directory, sbml_file), validate=validate)
# change back into working dir
os.chdir(working_dir)
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/iAB_RBC_283.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('{}_fba'.format(settings.MODEL_ID))
model.setName('{} (FBA)'.format(settings.MODEL_ID))
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)
# update the existing exchange reactions
builder.update_exchange_reactions(model, flux_unit=UNIT_FLUX)
# write SBML file
sbmlio.write_sbml(doc_fba,
filepath=pjoin(directory, sbml_file),
validate=True)
return doc_fba
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/iAB_RBC_283.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('{}_fba'.format(settings.MODEL_ID))
model.setName('{} (FBA)'.format(settings.MODEL_ID))
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)
# update the existing exchange reactions
builder.update_exchange_reactions(model, flux_unit=UNIT_FLUX)
# write SBML file
sbmlio.write_sbml(doc_fba, filepath=pjoin(directory, sbml_file), validate=True)
return doc_fba
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 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 = 'cell'
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=False, create_port=True)
# exchange bounds
builder.create_exchange_bounds(model_bounds=model, model_fba=model_fba, unit_flux=UNIT_FLUX, create_ports=True)
builder.create_dynamic_bounds(model_bounds=model, model_fba=model_fba, unit_flux=UNIT_FLUX)
# annotations
if annotations:
annotation.annotate_sbml_doc(doc, annotations)
sbmlio.write_sbml(doc, filepath=os.path.join(directory, sbml_file), validate=True)
def top_model(sbml_file, directory, emds, doc_fba, annotations=None):
""" Create top comp model.
Creates full comp model by combining fba, update and bounds
model with additional kinetics in the top model.
"""
top_notes = notes.format("""
<h2>TOP model</h2>
<p>Main comp DFBA model by combining fba, update and bounds
model with additional kinetics in the top model.</p>
""")
working_dir = os.getcwd()
os.chdir(directory)
doc = builder.template_doc_top(settings.MODEL_ID, emds)
model = doc.getModel()
utils.set_model_info(model,
notes=top_notes,
creators=creators, units=units, main_units=main_units)
# dt
builder.create_dfba_dt(model, step_size=DT_SIM, time_unit=UNIT_TIME, create_port=False)
# compartment
compartment_id = "cell"
builder.create_dfba_compartment(model, compartment_id=compartment_id, unit_volume=UNIT_VOLUME, create_port=False)
# dynamic species
model_fba = doc_fba.getModel()
builder.create_dfba_species(model, model_fba, compartment_id=compartment_id, hasOnlySubstanceUnits=False,
unit_amount=UNIT_AMOUNT, create_port=False)
# dummy species
builder.create_dummy_species(model, compartment_id=compartment_id, hasOnlySubstanceUnits=False,
unit_amount=UNIT_AMOUNT)
# exchange flux bounds
builder.create_exchange_bounds(model, model_fba=model_fba, unit_flux=UNIT_FLUX, create_ports=False)
# dummy reactions & flux assignments
builder.create_dummy_reactions(model, model_fba=model_fba, unit_flux=UNIT_FLUX)
# replacedBy (fba reactions)
builder.create_top_replacedBy(model, model_fba=model_fba)
# replaced
builder.create_top_replacements(model, model_fba, compartment_id=compartment_id)
objects = [
# kinetic parameters
mc.Parameter(sid="Vmax_RATP", value=1, unit=UNIT_FLUX, constant=True),
mc.Parameter(sid='k_RATP', value=0.1, unit=UNIT_CONCENTRATION, constant=True),
# balancing rules
mc.AssignmentRule(sid="atp_tot", value="atp + adp", unit=UNIT_CONCENTRATION),
mc.AssignmentRule(sid="c3_tot", value="2 dimensionless * glc + pyr", unit="mM")
]
mc.create_objects(model, objects)
ratp = mc.create_reaction(model, rid="RATP", name="atp -> adp", fast=False, reversible=False,
reactants={"atp": 1}, products={"adp": 1}, compartment=compartment_id,
formula='Vmax_RATP * atp/(k_RATP + atp)')
# initial concentrations for fba exchange species
initial_c = {
'atp': 2.0,
'adp': 1.0,
'glc': 5.0,
'pyr': 0.0
}
for sid, value in initial_c.items():
species = model.getSpecies(sid)
species.setInitialConcentration(value)
# write SBML file
if annotations:
annotation.annotate_sbml_doc(doc, annotations)
sbmlio.write_sbml(doc, filepath=os.path.join(directory, sbml_file), validate=True)
# change back the working dir
os.chdir(working_dir)
def top_model(sbml_file, directory, emds, doc_fba, annotations=None):
""" Create top comp model.
Creates full comp model by combining fba, update and bounds
model with additional kinetics in the top model.
"""
top_notes = notes.format("""
<h2>TOP model</h2>
<p>Main comp DFBA model by combining fba, update and bounds
model with additional kinetics in the top model.</p>
""")
working_dir = os.getcwd()
os.chdir(directory)
doc = builder.template_doc_top(settings.MODEL_ID, emds)
model = doc.getModel()
utils.set_model_info(model,
notes=top_notes,
creators=creators, units=units, main_units=main_units)
# dt
builder.create_dfba_dt(model, step_size=DT_SIM, time_unit=UNIT_TIME, create_port=False)
# compartment
compartment_id = "extern"
builder.create_dfba_compartment(model, compartment_id=compartment_id, unit_volume=UNIT_VOLUME, create_port=False)
# dynamic species
model_fba = doc_fba.getModel()
builder.create_dfba_species(model, model_fba, compartment_id=compartment_id, hasOnlySubstanceUnits=True,
unit_amount=UNIT_AMOUNT, create_port=False)
# dummy species
builder.create_dummy_species(model, compartment_id=compartment_id, hasOnlySubstanceUnits=True,
unit_amount=UNIT_AMOUNT)
# exchange flux bounds
builder.create_exchange_bounds(model, model_fba=model_fba, unit_flux=UNIT_FLUX, create_ports=False)
# dummy reactions & flux assignments
builder.create_dummy_reactions(model, model_fba=model_fba, unit_flux=UNIT_FLUX)
# replacedBy (fba reactions)
builder.create_top_replacedBy(model, model_fba=model_fba)
# replaced
builder.create_top_replacements(model, model_fba, compartment_id=compartment_id)
# initial concentrations for fba exchange species
initial_c = {
'A': 10.0,
'C': 0.0,
}
for sid, value in initial_c.items():
species = model.getSpecies(sid)
species.setInitialConcentration(value)
# kinetic model
mc.create_objects(model, [
# kinetic species
mc.Species(sid='D', initialConcentration=0, substanceUnit=UNIT_AMOUNT,
hasOnlySubstanceUnits=True, compartment="extern"),
# kinetic
mc.Parameter(sid="k_R4", value=0.1, constant=True, unit="per_s", sboTerm="SBO:0000009"),
# bounds parameter
mc.Parameter(sid='ub_R1', value=1.0, unit=UNIT_FLUX, constant=False, sboTerm="SBO:0000625"),
])
# kinetic reaction (MMK)
mc.create_reaction(model, rid="R4", name="R4: C -> D", fast=False, reversible=False,
reactants={"C": 1}, products={"D": 1}, formula="k_R4*C", compartment="extern")
# kinetic flux bounds
comp.replace_elements(model, 'ub_R1', ref_type=comp.SBASE_REF_TYPE_PORT,
replaced_elements={'bounds': ['ub_R1_port'],
'fba': ['ub_R1_port']})
# write SBML file
if annotations:
annotation.annotate_sbml_doc(doc, annotations)
sbmlio.write_sbml(doc, filepath=os.path.join(directory, sbml_file), validate=True)
# change back the working dir
os.chdir(working_dir)
def fba_model(sbml_file, directory, annotations=None):
""" FBA model
:param sbml_file: output file name
:param directory: output directory
:return: SBMLDocument
"""
fba_notes = notes.format("""
<h2>FBA submodel</h2>
<p>DFBA fba submodel. Unbalanced metabolites are encoded via exchange fluxes.</p>
""")
doc = builder.template_doc_fba(settings.MODEL_ID)
model = doc.getModel()
utils.set_model_info(model,
notes=fba_notes,
creators=creators,
units=units, main_units=main_units)
objects = [
# compartments
mc.Compartment(sid='cell', value=1.0, unit=UNIT_VOLUME, constant=True, name='cell', spatialDimensions=3),
# exchange species
mc.Species(sid='atp', name="ATP", initialConcentration=0, substanceUnit=UNIT_AMOUNT, hasOnlySubstanceUnits=False, compartment="cell"),
mc.Species(sid='adp', name="ADP", initialConcentration=0, substanceUnit=UNIT_AMOUNT, hasOnlySubstanceUnits=False, compartment="cell"),
mc.Species(sid='glc', name="Glucose", initialConcentration=0, substanceUnit=UNIT_AMOUNT, hasOnlySubstanceUnits=False, compartment="cell"),
mc.Species(sid='pyr', name='Pyruvate', initialConcentration=0, substanceUnit=UNIT_AMOUNT, hasOnlySubstanceUnits=False, compartment="cell"),
# internal species
mc.Species(sid='fru16bp', name='Fructose 1,6-bisphospate', initialConcentration=0, substanceUnit=UNIT_AMOUNT, hasOnlySubstanceUnits=False, compartment="cell"),
mc.Species(sid='pg2', name='2-Phosphoglycerate', initialConcentration=0, substanceUnit=UNIT_AMOUNT, hasOnlySubstanceUnits=False, compartment="cell"),
# bounds
mc.Parameter(sid="ub_R3", value=1.0, unit=UNIT_FLUX, constant=True, sboTerm=builder.FLUX_BOUND_SBO),
mc.Parameter(sid="zero", value=0.0, unit=UNIT_FLUX, constant=True, sboTerm=builder.FLUX_BOUND_SBO),
mc.Parameter(sid="ub_default", value=builder.UPPER_BOUND_DEFAULT, unit=UNIT_FLUX, constant=True,
sboTerm=builder.FLUX_BOUND_SBO),
]
mc.create_objects(model, objects)
# reactions
r1 = mc.create_reaction(model, rid="R1", name="glu + 2 atp -> fru16bp + 2 adp", fast=False, reversible=False,
reactants={"glc": 1, "atp": 2}, products={"fru16bp": 1, 'adp': 2}, compartment='cell')
r2 = mc.create_reaction(model, rid="R2", name="fru16bp -> 2 pg2", fast=False, reversible=False,
reactants={"fru16bp": 1}, products={"pg2": 2}, compartment='cell')
r3 = mc.create_reaction(model, rid="R3", name="pg2 + adp -> pyr + atp", fast=False, reversible=False,
reactants={"pg2": 1, "adp": 2}, products={"pyr": 1, "atp": 2}, compartment='cell')
# flux bounds
fbc.set_flux_bounds(r1, lb="zero", ub="ub_default")
fbc.set_flux_bounds(r2, lb="zero", ub="ub_default")
fbc.set_flux_bounds(r3, lb="zero", ub="ub_R3")
# fbc.set_flux_bounds(ratp, lb="zero", ub="ub_RATP")
# exchange reactions
for sid in ['atp', 'adp', 'glc', 'pyr']:
builder.create_exchange_reaction(model, species_id=sid, flux_unit=UNIT_FLUX)
# objective function
model_fbc = model.getPlugin("fbc")
fbc.create_objective(model_fbc, oid="RATP_maximize", otype="maximize", fluxObjectives={"R3": 1.0}, active=True)
if annotations:
annotation.annotate_sbml_doc(doc, annotations)
# write SBML
sbmlio.write_sbml(doc, filepath=os.path.join(directory, sbml_file), validate=True)
return doc
def fba_model(sbml_file, directory, annotations=None):
""" FBA model
:param sbml_file: output file name
:param directory: output directory
:return: SBMLDocument
"""
fba_notes = notes.format("""
<h2>FBA submodel</h2>
<p>DFBA fba submodel. Unbalanced metabolites are encoded via exchange fluxes.</p>
""")
doc = builder.template_doc_fba(settings.MODEL_ID)
model = doc.getModel()
utils.set_model_info(model,
notes=fba_notes,
creators=creators,
units=units, main_units=main_units)
objects = [
# compartments
mc.Compartment(sid='extern', value=1.0, unit=UNIT_VOLUME, constant=True, name='external compartment',
spatialDimensions=3),
mc.Compartment(sid='cell', value=1.0, unit=UNIT_VOLUME, constant=True, name='cell', spatialDimensions=3),
mc.Compartment(sid='membrane', value=1.0, unit=UNIT_AREA, constant=True, name='membrane', spatialDimensions=2),
# exchange species
mc.Species(sid='A', name="A", initialConcentration=0, substanceUnit=UNIT_AMOUNT, hasOnlySubstanceUnits=True,
compartment="extern"),
mc.Species(sid='C', name="C", initialConcentration=0, substanceUnit=UNIT_AMOUNT, hasOnlySubstanceUnits=True,
compartment="extern"),
# internal species
mc.Species(sid='B1', name="B1", initialConcentration=0, substanceUnit=UNIT_AMOUNT, hasOnlySubstanceUnits=True,
compartment="cell"),
mc.Species(sid='B2', name="B2", initialConcentration=0, substanceUnit=UNIT_AMOUNT, hasOnlySubstanceUnits=True,
compartment="cell"),
# bounds
mc.Parameter(sid="ub_R1", value=1.0, unit=UNIT_FLUX, constant=True, sboTerm=builder.FLUX_BOUND_SBO),
mc.Parameter(sid="zero", value=0.0, unit=UNIT_FLUX, constant=True, sboTerm=builder.FLUX_BOUND_SBO),
mc.Parameter(sid="ub_default", value=builder.UPPER_BOUND_DEFAULT, unit=UNIT_FLUX, constant=True,
sboTerm=builder.FLUX_BOUND_SBO),
]
mc.create_objects(model, objects)
# reactions
r1 = mc.create_reaction(model, rid="R1", name="A import (R1)", fast=False, reversible=True,
reactants={"A": 1}, products={"B1": 1}, compartment='membrane')
r2 = mc.create_reaction(model, rid="R2", name="B1 <-> B2 (R2)", fast=False, reversible=True,
reactants={"B1": 1}, products={"B2": 1}, compartment='cell')
r3 = mc.create_reaction(model, rid="R3", name="B2 export (R3)", fast=False, reversible=True,
reactants={"B2": 1}, products={"C": 1}, compartment='membrane')
# flux bounds
fbc.set_flux_bounds(r1, lb="zero", ub="ub_R1")
fbc.set_flux_bounds(r2, lb="zero", ub="ub_default")
fbc.set_flux_bounds(r3, lb="zero", ub="ub_default")
# exchange reactions
builder.create_exchange_reaction(model, species_id="A", flux_unit=UNIT_FLUX)
builder.create_exchange_reaction(model, species_id="C", flux_unit=UNIT_FLUX)
# objective function
model_fbc = model.getPlugin("fbc")
fbc.create_objective(model_fbc, oid="R3_maximize", otype="maximize",
fluxObjectives={"R3": 1.0}, active=True)
# create ports for kinetic bounds
comp.create_ports(model, portType=comp.PORT_TYPE_PORT,
idRefs=["ub_R1"])
# write SBML
if annotations:
annotation.annotate_sbml_doc(doc, annotations)
sbmlio.write_sbml(doc, filepath=os.path.join(directory, sbml_file), validate=True)
return doc
def top_model(sbml_file, directory, emds, doc_fba, annotations=None):
""" Create top comp model.
Creates full comp model by combining fba, update and bounds
model with additional kinetics in the top model.
"""
top_notes = notes.format("""
<h2>TOP model</h2>
<p>Main comp DFBA model by combining fba, update and bounds
model with additional kinetics in the top model.</p>
""")
working_dir = os.getcwd()
os.chdir(directory)
doc = builder.template_doc_top(settings.MODEL_ID, emds)
model = doc.getModel()
utils.set_model_info(model,
notes=top_notes,
creators=creators,
units=units,
main_units=main_units)
# dt
builder.create_dfba_dt(model,
step_size=DT_SIM,
time_unit=UNIT_TIME,
create_port=False)
# compartment
compartment_id = "extern"
builder.create_dfba_compartment(model,
compartment_id=compartment_id,
unit_volume=UNIT_VOLUME,
create_port=False)
# dynamic species
model_fba = doc_fba.getModel()
builder.create_dfba_species(model,
model_fba,
compartment_id=compartment_id,
hasOnlySubstanceUnits=True,
unit_amount=UNIT_AMOUNT,
create_port=False)
# dummy species
builder.create_dummy_species(model,
compartment_id=compartment_id,
hasOnlySubstanceUnits=True,
unit_amount=UNIT_AMOUNT)
# exchange flux bounds
builder.create_exchange_bounds(model,
model_fba=model_fba,
unit_flux=UNIT_FLUX,
create_ports=False)
# dummy reactions & flux assignments
builder.create_dummy_reactions(model,
model_fba=model_fba,
unit_flux=UNIT_FLUX)
# replacedBy (fba reactions)
builder.create_top_replacedBy(model, model_fba=model_fba)
# replaced
builder.create_top_replacements(model,
model_fba,
compartment_id=compartment_id)
# initial concentrations for fba exchange species
initial_c = {
'A': 10.0,
'C': 0.0,
}
for sid, value in initial_c.items():
species = model.getSpecies(sid)
species.setInitialConcentration(value)
# kinetic model
mc.create_objects(
model,
[
# kinetic species
mc.Species(sid='D',
initialConcentration=0,
substanceUnit=UNIT_AMOUNT,
hasOnlySubstanceUnits=True,
compartment="extern"),
# kinetic
mc.Parameter(sid="k_R4",
value=0.1,
constant=True,
unit="per_s",
sboTerm="SBO:0000009"),
# bounds parameter
mc.Parameter(sid='ub_R1',
value=1.0,
unit=UNIT_FLUX,
constant=False,
sboTerm="SBO:0000625"),
])
# kinetic reaction (MMK)
mc.create_reaction(model,
rid="R4",
name="R4: C -> D",
fast=False,
reversible=False,
reactants={"C": 1},
products={"D": 1},
formula="k_R4*C",
compartment="extern")
# kinetic flux bounds
comp.replace_elements(model,
'ub_R1',
ref_type=comp.SBASE_REF_TYPE_PORT,
replaced_elements={
'bounds': ['ub_R1_port'],
'fba': ['ub_R1_port']
})
# write SBML file
if annotations:
annotator.annotate_sbml_doc(doc, annotations)
sbml.write_sbml(doc,
filepath=os.path.join(directory, sbml_file),
validate=True)
# change back the working dir
os.chdir(working_dir)
def 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 top_model(sbml_file, directory, emds, doc_fba=None):
""" Create 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>
""")
# Necessary to change into directory with submodel files
working_dir = os.getcwd()
os.chdir(directory)
model_id = "ecoli"
doc = builder.template_doc_top(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)
# minimal medium with single carbon source
initial_c = {
'ac_e': 1.0,
'acald_e': 1.0,
'akg_e': 1.0,
'co2_e': 1.0,
'etoh_e': 1.0,
'for_e': 1.0,
'fru_e': 1.0,
'fum_e': 1.0,
'glc__D_e': 20.0,
'gln__L_e': 10.0,
'glu__L_e': 1.0,
'h_e': 1.0,
'h2o_e': 20.0,
'lac__D_e': 1.0,
'mal__L_e': 1.0,
'nh4_e': 1.0,
'o2_e': 1.0,
'pi_e': 1.0,
'pyr_e': 1.0,
'succ_e': 1.0,
'X': 0.001,
}
for sid, value in initial_c.items():
species = model.getSpecies(sid)
species.setInitialConcentration(value)
# 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)
# write SBML file
sbml.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):
""" 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
def top_model(sbml_file, directory, emds, doc_fba=None, annotations=None):
"""
Create diauxic comp model.
Test script for working with the comp extension in SBML.
One model composition combines all the kinetic models,
in addition the higher level comp model is created which combines everything (i.e. the FBA & ODE models).
For the simulation of the full combined model the tools have to figure out the subparts which are
simulated with which simulation environment.
Creates the full comp model as combination of FBA and comp models.
The submodels must already exist in the given directory
"""
top_notes = notes.format("""
<h2>TOP model</h2>
<p>Main comp DFBA model by combining fba, update and bounds
model with additional kinetics in the top model.</p>
""")
# Necessary to change into directory with submodel files
working_dir = os.getcwd()
os.chdir(directory)
doc = builder.template_doc_top(settings.MODEL_ID, emds)
model = doc.getModel()
utils.set_model_info(model, notes=top_notes,
creators=creators, units=units, main_units=main_units)
# dt
builder.create_dfba_dt(model, time_unit=UNIT_TIME, create_port=False)
# compartment
compartment_id = "bioreactor"
builder.create_dfba_compartment(model, compartment_id=compartment_id, unit_volume=UNIT_VOLUME, create_port=False)
# dynamic species
model_fba = doc_fba.getModel()
builder.create_dfba_species(model, model_fba, compartment_id=compartment_id, unit_amount=UNIT_AMOUNT,
create_port=False)
# dummy species
builder.create_dummy_species(model, compartment_id=compartment_id, unit_amount=UNIT_AMOUNT)
# exchange flux bounds
builder.create_exchange_bounds(model, model_fba=model_fba, unit_flux=UNIT_FLUX, create_ports=False)
# dummy reactions & flux assignments
builder.create_dummy_reactions(model, model_fba=model_fba, unit_flux=UNIT_FLUX)
# replacedBy (fba reactions)
builder.create_top_replacedBy(model, model_fba=model_fba)
# replaced
builder.create_top_replacements(model, model_fba, compartment_id=compartment_id)
# initial kinetic concentrations
initial_c = {
'Glcxt': 10.8,
'Ac': 0.4,
'O2': 0.21,
'X': 0.001,
}
for sid, value in initial_c.items():
species = model.getSpecies(sid)
species.setInitialConcentration(value)
objects = [
# biomass conversion factor
# mc.Parameter(sid="Y", name="biomass [g_per_l]", value=1.0, unit="g_per_l"),
# oxygen exchange parameters
mc.Parameter(sid="O2_ref", name="O2 reference", value=0.21, unit=UNIT_CONCENTRATION),
mc.Parameter(sid="kLa", name="O2 mass transfer", value=7.5, unit='per_h'),
]
mc.create_objects(model, objects)
# oxygen transfer reaction
mc.create_reaction(model, rid="vO2_transfer", name="oxygen transfer", reversible=True,
reactants={}, products={"O2": 1}, formula="kLa * (O2_ref-O2) * bioreactor",
compartment="bioreactor")
# write SBML file
if annotations:
annotation.annotate_sbml_doc(doc, annotations)
sbmlio.write_sbml(doc, filepath=os.path.join(directory, sbml_file), validate=True)
# change back into working dir
os.chdir(working_dir)
def fba_model(sbml_file, directory, annotations=None):
""" Create FBA submodel.
FBA submodel in sbml:fbc-version 2.
"""
fba_notes = notes.format("""
<h2>FBA submodel</h2>
<p>DFBA fba submodel. Unbalanced metabolites are encoded via exchange fluxes.</p>
""")
doc = builder.template_doc_fba(settings.MODEL_ID)
model = doc.getModel()
utils.set_model_info(model,
notes=fba_notes,
creators=creators,
units=units,
main_units=main_units)
objects = [
# compartments
Compartment(sid='bioreactor',
value=1.0,
unit=UNIT_VOLUME,
constant=True,
name='bioreactor',
spatialDimensions=3),
# species
Species(sid='Glcxt',
name="glucose",
initialConcentration=0.0,
substanceUnit=UNIT_AMOUNT,
hasOnlySubstanceUnits=False,
compartment="bioreactor"),
Species(sid='Ac',
name="acetate",
initialConcentration=0.0,
substanceUnit=UNIT_AMOUNT,
hasOnlySubstanceUnits=False,
compartment="bioreactor"),
Species(sid='O2',
name="oxygen",
initialConcentration=0.0,
substanceUnit=UNIT_AMOUNT,
hasOnlySubstanceUnits=False,
compartment="bioreactor"),
Species(sid='X',
name="biomass",
initialConcentration=0.0,
substanceUnit=UNIT_AMOUNT,
hasOnlySubstanceUnits=False,
compartment="bioreactor"),
# bounds
Parameter(sid="zero",
name="zero bound",
value=0.0,
unit=UNIT_FLUX_PER_G,
constant=True,
sboTerm="SBO:0000612"),
Parameter(sid="ub_default",
name="default upper bound",
value=builder.UPPER_BOUND_DEFAULT,
unit=UNIT_FLUX_PER_G,
constant=True,
sboTerm="SBO:0000612"),
Reaction(sid="v1",
name="v1 (39.43 Ac + 35 O2 -> X)",
reversible=False,
equation="39.43 Ac + 35 O2 -> X",
compartment='bioreactor',
lowerFluxBound="zero",
upperFluxBound="ub_default"),
Reaction(sid="v2",
name="v2 (9.46 Glcxt + 12.92 O2 -> X)",
reversible=False,
equation="9.46 Glcxt + 12.92 O2 -> X",
compartment='bioreactor',
lowerFluxBound="zero",
upperFluxBound="ub_default"),
Reaction(sid="v3",
name="v3 (9.84 Glcxt + 12.73 O2 -> 1.24 Ac + X)",
reversible=False,
equation="9.84 Glcxt + 12.73 O2 -> 1.24 Ac + X",
compartment='bioreactor',
lowerFluxBound="zero",
upperFluxBound="ub_default"),
Reaction(sid="v4",
name="v4 (19.23 Glcxt -> 12.12 Ac + X)",
reversible=False,
equation="19.23 Glcxt -> 12.12 Ac + X",
compartment='bioreactor',
lowerFluxBound="zero",
upperFluxBound="ub_default"),
]
factory.create_objects(model, objects)
# 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:
annotator.annotate_sbml_doc(doc, annotations)
sbmlio.write_sbml(doc, filepath=pjoin(directory, sbml_file), validate=True)
return doc
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):
""" FBA model
:param sbml_file: output file name
:param directory: output directory
:return: SBMLDocument
"""
fba_notes = notes.format("""
<h2>FBA submodel</h2>
<p>DFBA fba submodel. Unbalanced metabolites are encoded via exchange fluxes.</p>
""")
doc = builder.template_doc_fba(settings.MODEL_ID)
model = doc.getModel()
utils.set_model_info(model,
notes=fba_notes,
creators=creators,
units=units,
main_units=main_units)
objects = [
# compartments
mc.Compartment(sid='extern',
value=1.0,
unit=UNIT_VOLUME,
constant=True,
name='external compartment',
spatialDimensions=3),
mc.Compartment(sid='cell',
value=1.0,
unit=UNIT_VOLUME,
constant=True,
name='cell',
spatialDimensions=3),
mc.Compartment(sid='membrane',
value=1.0,
unit=UNIT_AREA,
constant=True,
name='membrane',
spatialDimensions=2),
# exchange species
mc.Species(sid='A',
name="A",
initialConcentration=0,
substanceUnit=UNIT_AMOUNT,
hasOnlySubstanceUnits=True,
compartment="extern"),
mc.Species(sid='C',
name="C",
initialConcentration=0,
substanceUnit=UNIT_AMOUNT,
hasOnlySubstanceUnits=True,
compartment="extern"),
# internal species
mc.Species(sid='B1',
name="B1",
initialConcentration=0,
substanceUnit=UNIT_AMOUNT,
hasOnlySubstanceUnits=True,
compartment="cell"),
mc.Species(sid='B2',
name="B2",
initialConcentration=0,
substanceUnit=UNIT_AMOUNT,
hasOnlySubstanceUnits=True,
compartment="cell"),
# bounds
mc.Parameter(sid="ub_R1",
value=1.0,
unit=UNIT_FLUX,
constant=True,
sboTerm=builder.FLUX_BOUND_SBO),
mc.Parameter(sid="zero",
value=0.0,
unit=UNIT_FLUX,
constant=True,
sboTerm=builder.FLUX_BOUND_SBO),
mc.Parameter(sid="ub_default",
value=builder.UPPER_BOUND_DEFAULT,
unit=UNIT_FLUX,
constant=True,
sboTerm=builder.FLUX_BOUND_SBO),
]
mc.create_objects(model, objects)
# reactions
r1 = mc.create_reaction(model,
rid="R1",
name="A import (R1)",
fast=False,
reversible=True,
reactants={"A": 1},
products={"B1": 1},
compartment='membrane')
r2 = mc.create_reaction(model,
rid="R2",
name="B1 <-> B2 (R2)",
fast=False,
reversible=True,
reactants={"B1": 1},
products={"B2": 1},
compartment='cell')
r3 = mc.create_reaction(model,
rid="R3",
name="B2 export (R3)",
fast=False,
reversible=True,
reactants={"B2": 1},
products={"C": 1},
compartment='membrane')
# flux bounds
fbc.set_flux_bounds(r1, lb="zero", ub="ub_R1")
fbc.set_flux_bounds(r2, lb="zero", ub="ub_default")
fbc.set_flux_bounds(r3, lb="zero", ub="ub_default")
# exchange reactions
builder.create_exchange_reaction(model,
species_id="A",
flux_unit=UNIT_FLUX)
builder.create_exchange_reaction(model,
species_id="C",
flux_unit=UNIT_FLUX)
# objective function
model_fbc = model.getPlugin("fbc")
fbc.create_objective(model_fbc,
oid="R3_maximize",
otype="maximize",
fluxObjectives={"R3": 1.0},
active=True)
# create ports for kinetic bounds
comp.create_ports(model, portType=comp.PORT_TYPE_PORT, idRefs=["ub_R1"])
# write SBML
if annotations:
annotator.annotate_sbml_doc(doc, annotations)
sbml.write_sbml(doc,
filepath=os.path.join(directory, sbml_file),
validate=True)
return doc
def top_model(sbml_file, directory, emds, doc_fba=None):
""" Create 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>
""")
# Necessary to change into directory with submodel files
working_dir = os.getcwd()
os.chdir(directory)
model_id = "ecoli"
doc = builder.template_doc_top(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)
# minimal medium with single carbon source
initial_c = {
'ac_e': 1.0,
'acald_e': 1.0,
'akg_e': 1.0,
'co2_e': 1.0,
'etoh_e': 1.0,
'for_e': 1.0,
'fru_e': 1.0,
'fum_e': 1.0,
'glc__D_e': 20.0,
'gln__L_e': 10.0,
'glu__L_e': 1.0,
'h_e': 1.0,
'h2o_e': 20.0,
'lac__D_e': 1.0,
'mal__L_e': 1.0,
'nh4_e': 1.0,
'o2_e': 1.0,
'pi_e': 1.0,
'pyr_e': 1.0,
'succ_e': 1.0,
'X': 0.001,
}
for sid, value in initial_c.items():
species = model.getSpecies(sid)
species.setInitialConcentration(value)
# 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)
# write SBML file
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):
""" 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 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 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 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
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)
