def test_create_exchange_reaction():
print(libsbml.getLibSBMLDottedVersion())
doc = create_fba_doc()
model = doc.getModel()
builder.create_exchange_reaction(model, species_id="A")
builder.create_exchange_reaction(model, species_id="B")
assert model.getNumReactions() == 2
ex_A = model.getReaction(builder.EXCHANGE_REACTION_PREFIX + "A")
assert ex_A
ex_B = model.getReaction(builder.EXCHANGE_REACTION_PREFIX + "B")
assert ex_B
comp_model = model.getPlugin("comp")
ports = comp_model.getListOfPorts()
assert ports is not None
assert comp_model.getNumPorts() == 6
assert comp_model.getPort(builder.EXCHANGE_REACTION_PREFIX + "A_port")
assert comp_model.getPort(builder.EXCHANGE_REACTION_PREFIX + "B_port")
assert comp_model.getPort(builder.LOWER_BOUND_PREFIX + builder.EXCHANGE_REACTION_PREFIX + "A_port")
assert comp_model.getPort(builder.LOWER_BOUND_PREFIX + builder.EXCHANGE_REACTION_PREFIX + "B_port")
assert comp_model.getPort(builder.UPPER_BOUND_PREFIX + builder.EXCHANGE_REACTION_PREFIX + "A_port")
assert comp_model.getPort(builder.UPPER_BOUND_PREFIX + builder.EXCHANGE_REACTION_PREFIX + "B_port")
fbc_ex_A = ex_A.getPlugin("fbc")
assert fbc_ex_A
fbc_ex_B = ex_B.getPlugin("fbc")
assert fbc_ex_B
def test_create_exchange_reaction():
print(libsbml.getLibSBMLDottedVersion())
doc = create_fba_doc()
model = doc.getModel()
builder.create_exchange_reaction(model, species_id="A")
builder.create_exchange_reaction(model, species_id="B")
assert model.getNumReactions() == 2
ex_A = model.getReaction(builder.EXCHANGE_REACTION_PREFIX + "A")
assert ex_A
ex_B = model.getReaction(builder.EXCHANGE_REACTION_PREFIX + "B")
assert ex_B
comp_model = model.getPlugin("comp")
ports = comp_model.getListOfPorts()
assert ports is not None
assert comp_model.getNumPorts() == 6
assert comp_model.getPort(builder.EXCHANGE_REACTION_PREFIX + "A_port")
assert comp_model.getPort(builder.EXCHANGE_REACTION_PREFIX + "B_port")
assert comp_model.getPort(builder.LOWER_BOUND_PREFIX +
builder.EXCHANGE_REACTION_PREFIX + "A_port")
assert comp_model.getPort(builder.LOWER_BOUND_PREFIX +
builder.EXCHANGE_REACTION_PREFIX + "B_port")
assert comp_model.getPort(builder.UPPER_BOUND_PREFIX +
builder.EXCHANGE_REACTION_PREFIX + "A_port")
assert comp_model.getPort(builder.UPPER_BOUND_PREFIX +
builder.EXCHANGE_REACTION_PREFIX + "B_port")
fbc_ex_A = ex_A.getPlugin("fbc")
assert fbc_ex_A
fbc_ex_B = ex_B.getPlugin("fbc")
assert fbc_ex_B
def test_create_directed_exchange_reaction():
doc = create_fba_doc()
model = doc.getModel()
builder.create_exchange_reaction(model,
species_id="A",
exchange_type=builder.EXCHANGE_IMPORT)
builder.create_exchange_reaction(model,
species_id="B",
exchange_type=builder.EXCHANGE_EXPORT)
assert model.getNumReactions() == 2
# import
ex_A = model.getReaction(builder.EXCHANGE_REACTION_PREFIX + "A")
assert ex_A
fbc_ex_A = ex_A.getPlugin("fbc")
assert fbc_ex_A
pid_ub = fbc_ex_A.getUpperFluxBound()
p_ub = model.getParameter(pid_ub)
assert p_ub
assert p_ub.value == builder.ZERO_BOUND
pid_lb = fbc_ex_A.getLowerFluxBound()
p_lb = model.getParameter(pid_lb)
assert p_lb
assert p_lb.value == builder.LOWER_BOUND_DEFAULT
# export
ex_B = model.getReaction(builder.EXCHANGE_REACTION_PREFIX + "B")
assert ex_B
fbc_ex_B = ex_B.getPlugin("fbc")
assert fbc_ex_B
pid_ub = fbc_ex_B.getUpperFluxBound()
p_ub = model.getParameter(pid_ub)
assert p_ub
assert p_ub.value == builder.UPPER_BOUND_DEFAULT
pid_lb = fbc_ex_B.getLowerFluxBound()
p_lb = model.getParameter(pid_lb)
assert p_lb
assert p_lb.value == builder.ZERO_BOUND
def test_create_directed_exchange_reaction():
doc = create_fba_doc()
model = doc.getModel()
builder.create_exchange_reaction(model, species_id="A", exchange_type=builder.EXCHANGE_IMPORT)
builder.create_exchange_reaction(model, species_id="B", exchange_type=builder.EXCHANGE_EXPORT)
assert model.getNumReactions() == 2
# import
ex_A = model.getReaction(builder.EXCHANGE_REACTION_PREFIX + "A")
assert ex_A
fbc_ex_A = ex_A.getPlugin("fbc")
assert fbc_ex_A
pid_ub = fbc_ex_A.getUpperFluxBound()
p_ub = model.getParameter(pid_ub)
assert p_ub
assert p_ub.value == builder.ZERO_BOUND
pid_lb = fbc_ex_A.getLowerFluxBound()
p_lb = model.getParameter(pid_lb)
assert p_lb
assert p_lb.value == builder.LOWER_BOUND_DEFAULT
# export
ex_B = model.getReaction(builder.EXCHANGE_REACTION_PREFIX + "B")
assert ex_B
fbc_ex_B = ex_B.getPlugin("fbc")
assert fbc_ex_B
pid_ub = fbc_ex_B.getUpperFluxBound()
p_ub = model.getParameter(pid_ub)
assert p_ub
assert p_ub.value == builder.UPPER_BOUND_DEFAULT
pid_lb = fbc_ex_B.getLowerFluxBound()
p_lb = model.getParameter(pid_lb)
assert p_lb
assert p_lb.value == builder.ZERO_BOUND
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):
""" 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, 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 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 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 = 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):
""" 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
# reactions
r1 = factory.create_reaction(model, rid="R1", name="A import (R1)", fast=False, reversible=True,
reactants={"A": 1}, products={"B1": 1}, compartment='membrane')
r2 = factory.create_reaction(model, rid="R2", name="B1 <-> B2 (R2)", fast=False, reversible=True,
reactants={"B1": 1}, products={"B2": 1}, compartment='cell')
r3 = factory.create_reaction(model, rid="R3", name="B2 export (R3)", fast=False, reversible=True,
reactants={"B2": 1}, products={"C": 1}, compartment='membrane')
# flux bounds
fbc.set_flux_bounds(r1, lb="zero", ub="ub_R1")
fbc.set_flux_bounds(r2, lb="zero", ub="ub_default")
fbc.set_flux_bounds(r3, lb="zero", ub="ub_default")
# exchange reactions
builder.create_exchange_reaction(model, species_id="A", flux_unit=UNIT_FLUX)
builder.create_exchange_reaction(model, species_id="C", flux_unit=UNIT_FLUX)
# objective function
model_fbc = model.getPlugin("fbc")
fbc.create_objective(model_fbc, oid="R3_maximize", otype="maximize",
fluxObjectives={"R3": 1.0}, active=True)
# write SBML file
import tempfile
sbml_file = tempfile.NamedTemporaryFile(suffix=".xml")
sbmlio.write_sbml(doc=doc, filepath=sbml_file.name)
# In[ ]:
def test_modelcreator_notebook():
"""
If this test fails the respective notebook must be updated:
:return:
"""
import libsbml
from libsbml import (UNIT_KIND_SECOND, UNIT_KIND_ITEM, UNIT_KIND_MOLE,
UNIT_KIND_KILOGRAM, UNIT_KIND_METRE, UNIT_KIND_LITRE)
from sbmlutils import comp
from sbmlutils import fbc
from sbmlutils import sbmlio
from sbmlutils import factory as fac
from sbmlutils.dfba import builder, utils
main_units = {
'time': 's',
'extent': UNIT_KIND_ITEM,
'substance': UNIT_KIND_ITEM,
'length': 'm',
'area': 'm2',
'volume': 'm3',
}
units = [
fac.Unit('s', [(UNIT_KIND_SECOND, 1.0)]),
fac.Unit('item', [(UNIT_KIND_ITEM, 1.0)]),
fac.Unit('kg', [(UNIT_KIND_KILOGRAM, 1.0)]),
fac.Unit('m', [(UNIT_KIND_METRE, 1.0)]),
fac.Unit('m2', [(UNIT_KIND_METRE, 2.0)]),
fac.Unit('m3', [(UNIT_KIND_METRE, 3.0)]),
fac.Unit('mM', [(UNIT_KIND_MOLE, 1.0, 0),
(UNIT_KIND_METRE, -3.0)]),
fac.Unit('per_s', [(UNIT_KIND_SECOND, -1.0)]),
fac.Unit('item_per_s', [(UNIT_KIND_ITEM, 1.0),
(UNIT_KIND_SECOND, -1.0)]),
fac.Unit('item_per_m3', [(UNIT_KIND_ITEM, 1.0),
(UNIT_KIND_METRE, -3.0)]),
]
UNIT_TIME = 's'
UNIT_AMOUNT = 'item'
UNIT_AREA = 'm2'
UNIT_VOLUME = 'm3'
UNIT_CONCENTRATION = 'item_per_m3'
UNIT_FLUX = 'item_per_s'
# Create SBMLDocument with fba
doc = builder.template_doc_fba(model_id="toy")
model = doc.getModel()
utils.set_units(model, units)
utils.set_main_units(model, main_units)
objects = [
# compartments
fac.Compartment(sid='extern', value=1.0, unit=UNIT_VOLUME, constant=True, name='external compartment',
spatialDimensions=3),
fac.Compartment(sid='cell', value=1.0, unit=UNIT_VOLUME, constant=True, name='cell', spatialDimensions=3),
fac.Compartment(sid='membrane', value=1.0, unit=UNIT_AREA, constant=True, name='membrane', spatialDimensions=2),
# exchange species
fac.Species(sid='A', name="A", value=0, substanceUnit=UNIT_AMOUNT, hasOnlySubstanceUnits=True,
compartment="extern"),
fac.Species(sid='C', name="C", value=0, substanceUnit=UNIT_AMOUNT, hasOnlySubstanceUnits=True,
compartment="extern"),
# internal species
fac.Species(sid='B1', name="B1", value=0, substanceUnit=UNIT_AMOUNT, hasOnlySubstanceUnits=True,
compartment="cell"),
fac.Species(sid='B2', name="B2", value=0, substanceUnit=UNIT_AMOUNT, hasOnlySubstanceUnits=True,
compartment="cell"),
# bounds
fac.Parameter(sid="ub_R1", value=1.0, unit=UNIT_FLUX, constant=True, sboTerm=builder.FLUX_BOUND_SBO),
fac.Parameter(sid="zero", value=0.0, unit=UNIT_FLUX, constant=True, sboTerm=builder.FLUX_BOUND_SBO),
fac.Parameter(sid="ub_default", value=builder.UPPER_BOUND_DEFAULT, unit=UNIT_FLUX, constant=True,
sboTerm=builder.FLUX_BOUND_SBO),
]
fac.create_objects(model, objects)
# reactions
r1 = fac.create_reaction(model, rid="R1", name="A import (R1)", fast=False, reversible=True,
reactants={"A": 1}, products={"B1": 1}, compartment='membrane')
r2 = fac.create_reaction(model, rid="R2", name="B1 <-> B2 (R2)", fast=False, reversible=True,
reactants={"B1": 1}, products={"B2": 1}, compartment='cell')
r3 = fac.create_reaction(model, rid="R3", name="B2 export (R3)", fast=False, reversible=True,
reactants={"B2": 1}, products={"C": 1}, compartment='membrane')
# flux bounds
fbc.set_flux_bounds(r1, lb="zero", ub="ub_R1")
fbc.set_flux_bounds(r2, lb="zero", ub="ub_default")
fbc.set_flux_bounds(r3, lb="zero", ub="ub_default")
# exchange reactions
builder.create_exchange_reaction(model, species_id="A", flux_unit=UNIT_FLUX)
builder.create_exchange_reaction(model, species_id="C", flux_unit=UNIT_FLUX)
# objective function
model_fbc = model.getPlugin("fbc")
fac.create_objective(model_fbc, oid="R3_maximize", otype="maximize",
fluxObjectives={"R3": 1.0}, active=True)
# write SBML file
import tempfile
sbml_file = tempfile.NamedTemporaryFile(suffix=".xml")
sbmlio.write_sbml(doc=doc, filepath=sbml_file.name)
# reactions
Reaction(sid="R1", name="A import (R1)",
equation="A <-> B1", compartment='membrane', lowerFluxBound="zero", upperFluxBound="ub_R1"),
Reaction(sid="R2", name="B1 <-> B2 (R2)",
equation="B1 <-> B2", compartment='cell',
lowerFluxBound="zero", upperFluxBound="ub_default"),
Reaction(sid="R3", name="B2 export (R3)", fast=False, reversible=True,
equation="B2 <-> C", compartment='membrane',
lowerFluxBound="zero", upperFluxBound="ub_default"
),
]
factory.create_objects(model, objects)
# 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)
# write SBML file
import tempfile
sbml_file = tempfile.NamedTemporaryFile(suffix=".xml")
sbmlio.write_sbml(doc=doc, filepath=sbml_file.name)
# In[ ]:
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