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