def create_top_replacements(model, model_fba, compartment_id):
""" Create all the replacements in the top model.
:param model:
:param model_fba:
:param compartment_id:
:return:
"""
# compartment
comp.replace_elements(model, compartment_id, ref_type=comp.SBASE_REF_TYPE_PORT,
replaced_elements={
'update': ['{}_port'.format(compartment_id)],
'bounds': ['{}_port'.format(compartment_id)]})
# dt
comp.replace_elements(model, 'dt', ref_type=comp.SBASE_REF_TYPE_PORT,
replaced_elements={'bounds': ['dt_port']})
# species dependent replacements
ex_rids = utils.find_exchange_reactions(model_fba)
for ex_rid, sid in ex_rids.items():
# flux parameters
comp.replace_elements(model, FLUX_PARAMETER_PREFIX + sid, ref_type=comp.SBASE_REF_TYPE_PORT,
replaced_elements={'update': ['{}_port'.format(FLUX_PARAMETER_PREFIX + sid)]})
# dynamic species
comp.replace_elements(model, sid, ref_type=comp.SBASE_REF_TYPE_PORT,
replaced_elements={
'bounds': ['{}_port'.format(sid)],
'update': ['{}_port'.format(sid)]})
# bounds of exchange reactions
for replace_id in [
UPPER_BOUND_PREFIX + EXCHANGE_REACTION_PREFIX + sid,
LOWER_BOUND_PREFIX + EXCHANGE_REACTION_PREFIX + sid]:
comp.replace_elements(model, replace_id, ref_type=comp.SBASE_REF_TYPE_PORT,
replaced_elements={
'bounds': ['{}_port'.format(replace_id)],
'fba': ['{}_port'.format(replace_id)]})
# replace units
for unit in model.getListOfUnitDefinitions():
uid = unit.getId()
comp.replace_element_in_submodels(model, uid, ref_type=comp.SBASE_REF_TYPE_UNIT,
submodels=['bounds', 'fba', 'update'])
def create_top_replacements(model, model_fba, compartment_id):
""" Create all the replacements in the top model.
:param model:
:param model_fba:
:param compartment_id:
:return:
"""
# compartment
comp.replace_elements(model,
compartment_id,
ref_type=comp.SBASE_REF_TYPE_PORT,
replaced_elements={
'update': ['{}_port'.format(compartment_id)],
'bounds': ['{}_port'.format(compartment_id)]
})
# dt
comp.replace_elements(model,
'dt',
ref_type=comp.SBASE_REF_TYPE_PORT,
replaced_elements={'bounds': ['dt_port']})
# species dependent replacements
ex_rids = utils.find_exchange_reactions(model_fba)
for ex_rid, sid in ex_rids.items():
# flux parameters
comp.replace_elements(
model,
FLUX_PARAMETER_PREFIX + sid,
ref_type=comp.SBASE_REF_TYPE_PORT,
replaced_elements={
'update': ['{}_port'.format(FLUX_PARAMETER_PREFIX + sid)]
})
# dynamic species
comp.replace_elements(model,
sid,
ref_type=comp.SBASE_REF_TYPE_PORT,
replaced_elements={
'bounds': ['{}_port'.format(sid)],
'update': ['{}_port'.format(sid)]
})
# bounds of exchange reactions
for replace_id in [
UPPER_BOUND_PREFIX + EXCHANGE_REACTION_PREFIX + sid,
LOWER_BOUND_PREFIX + EXCHANGE_REACTION_PREFIX + sid
]:
comp.replace_elements(model,
replace_id,
ref_type=comp.SBASE_REF_TYPE_PORT,
replaced_elements={
'bounds': ['{}_port'.format(replace_id)],
'fba': ['{}_port'.format(replace_id)]
})
# replace units
for unit in model.getListOfUnitDefinitions():
uid = unit.getId()
comp.replace_element_in_submodels(
model,
uid,
ref_type=comp.SBASE_REF_TYPE_UNIT,
submodels=['bounds', 'fba', 'update'])
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 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 create_top_level_model(sbml_file):
"""
Creates the full comp model as combination of FBA and comp models.
connections
------------
[1] flux bounds
kinetic reaction bounds => replace the FBA bounds
comp_ode.submodel_bounds__ub_R1 => fba_R1.upper_bound
[2] reaction rates (fluxes)
FBA flux (all reactions) => replaces Reaction flux in kinetic model
** FBA **
<listOfParameters>
<parameter id="ub_R1" name="ub R1" value="1" units="item_per_s" constant="false"/>
<parameter id="lb" name="lower bound" value="0" units="item_per_s" constant="true"/>
<parameter id="ub" name="upper bound" value="1000" units="item_per_s" constant="true"/>
<parameter id="v_R1" name="R1 flux" value="0" units="item_per_s" constant="false"/>
<parameter id="v_R2" name="R2 flux" value="0" units="item_per_s" constant="false"/>
<parameter id="v_R3" name="R3 flux" value="0" units="item_per_s" constant="false"/>
</listOfParameters>
"""
sbmlns = SBMLNamespaces(3, 1, "comp", 1)
doc = SBMLDocument(sbmlns)
doc.setPackageRequired("comp", True)
doc.setPackageRequired("fbc", False)
mdoc = doc.getPlugin("comp")
# create listOfExternalModelDefinitions
emd_bounds = comp.create_ExternalModelDefinition(mdoc,
"toy_ode_bounds",
sbml_file=ode_bounds_file)
emd_fba = comp.create_ExternalModelDefinition(mdoc,
"toy_fba",
sbml_file=fba_file)
emd_update = comp.create_ExternalModelDefinition(mdoc,
"toy_ode_update",
sbml_file=ode_update_file)
emd_model = comp.create_ExternalModelDefinition(mdoc,
"toy_ode_model",
sbml_file=ode_model_file)
# create models and submodels
model = doc.createModel()
model.setId("toy_top_level")
model.setName("Top level model")
model_factory.add_generic_info(model)
mplugin = model.getPlugin("comp")
model.setSBOTerm(comp.SBO_CONTINOUS_FRAMEWORK)
# add submodel which references the external model definition
comp.add_submodel_from_emd(mplugin, submodel_sid="bounds", emd=emd_bounds)
comp.add_submodel_from_emd(mplugin, submodel_sid="fba", emd=emd_fba)
comp.add_submodel_from_emd(mplugin, submodel_sid="update", emd=emd_update)
comp.add_submodel_from_emd(mplugin, submodel_sid="model", emd=emd_model)
# --- compartments ---
create_compartments(model, [{
A_ID: "extern",
A_NAME: "external compartment",
A_VALUE: 1.0,
A_SPATIAL_DIMENSION: 3,
A_UNIT: model_factory.UNIT_VOLUME
}, {
A_ID: 'cell',
A_NAME: 'cell',
A_VALUE: 1.0,
A_SPATIAL_DIMENSION: 3,
A_UNIT: model_factory.UNIT_VOLUME
}])
# --- species ---
# replaced species
# (fba species are not replaced, because they need their boundaryConditions for the FBA,
# and do not depend on the actual concentrations)
create_species(model, [
{
A_ID: 'C',
A_NAME: "C",
A_VALUE: 0,
A_UNIT: model_factory.UNIT_AMOUNT,
A_HAS_ONLY_SUBSTANCE_UNITS: True,
A_COMPARTMENT: "extern"
},
])
# --- parameters ---
create_parameters(
model,
[
# bounds
{
A_ID: 'ub_R1',
A_VALUE: 1.0,
A_UNIT: model_factory.UNIT_FLUX,
A_NAME: 'ub_R1',
A_CONSTANT: False
},
{
A_ID: "vR3",
A_NAME: "vR3 (FBA flux)",
A_VALUE: 0.1,
A_UNIT: model_factory.UNIT_FLUX,
A_CONSTANT: False
}
])
# --- reactions ---
# dummy reaction in top model
r1 = create_reaction(model,
rid="R3",
name="R3 dummy",
fast=False,
reversible=True,
reactants={},
products={"C": 1},
compartment="extern")
# assignment rule
create_assignment_rules(model, [{A_ID: "vR3", A_VALUE: "R3"}])
# --- replacements ---
# replace compartments
comp.replace_elements(model,
'extern',
ref_type=comp.SBASE_REF_TYPE_PORT,
replaced_elements={
'fba': ['extern_port'],
'update': ['extern_port'],
'model': ['extern_port']
})
comp.replace_elements(model,
'cell',
ref_type=comp.SBASE_REF_TYPE_PORT,
replaced_elements={'fba': ['cell_port']})
# replace parameters
comp.replace_elements(model,
'ub_R1',
ref_type=comp.SBASE_REF_TYPE_PORT,
replaced_elements={
'bounds': ['ub_R1_port'],
'fba': ['ub_R1_port']
})
comp.replace_elements(model,
'vR3',
ref_type=comp.SBASE_REF_TYPE_PORT,
replaced_elements={'update': ['vR3_port']})
# replace species
comp.replace_elements(model,
'C',
ref_type=comp.SBASE_REF_TYPE_PORT,
replaced_elements={
'fba': ['C_port'],
'update': ['C_port'],
'model': ['C_port']
})
# replace reaction by fba reaction
comp.replaced_by(model,
'R3',
ref_type=comp.SBASE_REF_TYPE_PORT,
submodel='fba',
replaced_by="R3_port")
# replace units
for uid in [
's', 'kg', 'm3', 'm2', 'mM', 'item_per_m3', 'm', 'per_s',
'item_per_s'
]:
comp.replace_element_in_submodels(
model,
uid,
ref_type=comp.SBASE_REF_TYPE_UNIT,
submodels=['bounds', 'fba', 'update', 'model'])
# write SBML file
sbml_io.write_and_check(doc, sbml_file)