Ejemplo n.º 1
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 def fva(self) -> pd.DataFrame:
     model = self.read_model()
     result = fba(model)
     fluxes = result.fluxes
     try:
         fva_result = flux_variability_analysis(
             model, reactions=model.reactions, fraction_of_optimum=1.0
         )  # type: FluxVariabilityResult
         df = fva_result.data_frame
         df_out = pd.DataFrame(
             {
                 "model": self.model_path.name,
                 "objective": self.objective_id,
                 "reaction": df.index,
                 "flux": fluxes,
                 "status": CuratorConstants.STATUS_OPTIMAL,
                 "minimum": df.lower_bound,
                 "maximum": df.upper_bound,
             }
         )
     except Exception as e:
         logger.error(f"{e}")
         df_out = pd.DataFrame(
             {
                 "model": self.model_path.name,
                 "objective": self.objective_id,
                 "reaction": [r.id for r in model.reactions],
                 "flux": fluxes,
                 "status": CuratorConstants.STATUS_INFEASIBLE,
                 "minimum": CuratorConstants.VALUE_INFEASIBLE,
                 "maximum": CuratorConstants.VALUE_INFEASIBLE,
             }
         )
     return df_out
Ejemplo n.º 2
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    def reaction_deletion(self) -> pd.DataFrame:
        model = self.read_model()
        reaction_status = []
        reaction_values = []

        for reaction in model.reactions:
            reaction_bounds = (reaction.lower_bound, reaction.upper_bound)
            reaction.bounds = (0, 0)

            # run fba
            try:
                result = fba(model)
                value = result.objective_value
                status = CuratorConstants.STATUS_OPTIMAL
            except Exception as e:
                logger.error(f"{e}")
                value = CuratorConstants.VALUE_INFEASIBLE
                status = CuratorConstants.STATUS_INFEASIBLE

            reaction_status.append(status)
            reaction_values.append(value)

            # restore bounds
            reaction.bounds = reaction_bounds[:]

        return pd.DataFrame(
            {
                "model": self.model_path.name,
                "objective": self.objective_id,
                "reaction": [r.id for r in model.reactions],
                "status": reaction_status,
                "value": reaction_values,
            }
        )
def optimize_models_cameo(model_paths: List[Path]) -> pd.DataFrame:
    """FBA optimization for all given models."""
    results = []
    n_models = len(model_paths)
    for k, path in enumerate(model_paths):
        # load model
        start_time = time.time()
        model = read_sbml_model(str(path))
        load_time = time.time() - start_time  # [s]

        # run optimization
        start_time = time.time()
        result = fba(model)
        simulate_time = time.time() - start_time  # [s]
        objective_value = result.objective_value
        filename = path.name
        model = filename.split(".")[0]
        res = (model, objective_value, load_time, simulate_time)
        results.append(res)

        print("[{}/{}]".format(k, n_models), res)

    return pd.DataFrame(data=results,
                        columns=("model", "objective_value", "load_time",
                                 "simulate_time"))
Ejemplo n.º 4
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def write_results():
  """optimize results and write out to a file"""
  from cameo import load_model, fba
  
  outF = open("KOFBAFluxes-2.txt","w")
  
  model = load_model('KOmodel.json')
  print(len(model.genes))
  print(len(model.metabolites))
  print(len(model.reactions))
  # new_solution = model.optimize()
  fba_result = fba(model)
  print(fba_result)
  # print(fba_result.data_frame)
  print(len(fba_result.data_frame))
  # print(model.reactions)
    
  print(dir(fba_result))
  print(fba_result.data_frame)
  fbaD = fba_result.data_frame.T.to_dict()
  fbaCorrD = {}
  for keyS, valueF in fbaD.items():
    fbaCorrD[keyS] = valueF["flux"]
 
  for keyS, valueF in fbaCorrD.items():
    # print(keyS, valueF)
    outF.write(str(keyS) + ", " + str(valueF) + "\n")
 def test_apply_designs(self, model, diff_fva):
     result = diff_fva.run()
     works = []
     for strain_design in result:
         with model:
             strain_design.apply(model)
             try:
                 solution = fba(model, objective="Biomass_Ecoli_core_N_lp_w_fsh_GAM_rp__Nmet2")
                 works.append(solution["EX_succ_lp_e_rp_"] > 1e-6 and solution.objective_value > 1e-6)
             except Infeasible:
                 works.append(False)
     assert any(works)
Ejemplo n.º 6
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 def evaluate_design(model, strain_design, pathway, aerobic, bpcy, pyield):
     with TimeMachine() as tm:
         if not aerobic and 'EX_o2_e' in model.reactions:
             model.reactions.EX_o2_e.change_bounds(lb=0, time_machine=tm)
         pathway.apply(model, time_machine=tm)
         strain_design.apply(model, time_machine=tm)
         try:
             solution = fba(model, objective=model.biomass)
             _bpcy = bpcy(model, solution, strain_design.targets)
             _pyield = pyield(model, solution, strain_design.targets)
             target_flux = solution.fluxes[pyield.product]
             biomass = solution.fluxes[bpcy.biomass]
         except SolveError:
             _bpcy, _pyield, target_flux, biomass = np.nan, np.nan, np.nan, np.nan
         return _bpcy, _pyield, target_flux, biomass
Ejemplo n.º 7
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    def fba(self,
            measured_metabolites,
            filter_by_subsystem=False,
            add_constraints=False):
        if add_constraints:
            self.increasing_metabolite_constrains(measured_metabolites)

        if measured_metabolites is not None:
            self.set_objective_coefficients(measured_metabolites)

        reactions = None
        if filter_by_subsystem:
            reactions = self.filter_reaction_by_subsystems()

        return fba(self, reactions=reactions)
Ejemplo n.º 8
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 def evaluate_design(model, strain_design, pathway, aerobic, bpcy, pyield):
     with model:
         if not aerobic and 'EX_o2_e' in model.reactions:
             model.reactions.EX_o2_e.lower_bound = 0
         pathway.apply(model)
         strain_design.apply(model)
         try:
             solution = fba(model, objective=model.biomass)
             _bpcy = bpcy(model, solution, strain_design.targets)
             _pyield = pyield(model, solution, strain_design.targets)
             target_flux = solution.fluxes[pyield.product]
             biomass = solution.fluxes[bpcy.biomass]
         except OptimizationError:
             _bpcy, _pyield, target_flux, biomass = np.nan, np.nan, np.nan, np.nan
         return _bpcy, _pyield, target_flux, biomass
Ejemplo n.º 9
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 def evaluate_design(model, strain_design, pathway, aerobic, bpcy, pyield):
     with model:
         if not aerobic and 'EX_o2_e' in model.reactions:
             model.reactions.EX_o2_e.lower_bound = 0
         pathway.apply(model)
         strain_design.apply(model)
         try:
             solution = fba(model, objective=model.biomass)
             _bpcy = bpcy(model, solution, strain_design.targets)
             _pyield = pyield(model, solution, strain_design.targets)
             target_flux = solution.fluxes[pyield.product]
             biomass = solution.fluxes[bpcy.biomass]
         except OptimizationError:
             _bpcy, _pyield, target_flux, biomass = np.nan, np.nan, np.nan, np.nan
         return _bpcy, _pyield, target_flux, biomass
Ejemplo n.º 10
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 def test_apply_designs(self, model, diff_fva):
     result = diff_fva.run()
     works = []
     for strain_design in result:
         with model:
             strain_design.apply(model)
             try:
                 solution = fba(
                     model,
                     objective="Biomass_Ecoli_core_N_lp_w_fsh_GAM_rp__Nmet2"
                 )
                 works.append(solution["EX_succ_lp_e_rp_"] > 1e-6
                              and solution.objective_value > 1e-6)
             except Infeasible:
                 works.append(False)
     assert any(works)
 def test_apply_designs(self, model):
     result = DifferentialFVA(model,
                              model.reactions.EX_succ_lp_e_rp_,
                              points=5).run()
     works = []
     for strain_design in result:
         with TimeMachine() as tm:
             strain_design.apply(model, tm)
             try:
                 solution = fba(
                     model,
                     objective="Biomass_Ecoli_core_N_lp_w_fsh_GAM_rp__Nmet2"
                 )
                 works.append(solution["EX_succ_lp_e_rp_"] > 1e-6
                              and solution.objective_value > 1e-6)
             except Infeasible:
                 works.append(False)
     assert any(works)
Ejemplo n.º 12
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def _fba(model, analysis):
    '''!
    Private function - to simulate a model using Flux Balance 
    Analysis (FBA) or FBA-related methods, with Cameo.

    @model String: Model acceptable by Cameo (see 
    http://cameo.bio/02-import-models.html).
    @analysis String: Type of FBA to perform. Allowable types are 
    FBA (standard flux balance analysis) and pFBA (parsimonious 
    FBA). 
    '''
    import cameo
    if analysis == 'FBA':
        print('Run flux balance analysis on model %s' % str(model))
        return cameo.fba(model)
    elif analysis == 'pFBA':
        print('Run parsimonious flux balance analysis on model %s' \
              % str(model))
        return cameo.pfba(model)
Ejemplo n.º 13
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    def gene_deletion(self) -> pd.DataFrame:
        model = self.read_model()
        gene_status = []
        gene_values = []

        knockout_reactions = self.knockout_reactions_for_genes(self.model_path)

        for gene in model.genes:
            reaction_bounds = dict()
            # knockout all reactions affected by gene by setting bounds zero
            for rid in knockout_reactions[gene.id]:
                reaction = model.reactions.get_by_id(rid)
                reaction_bounds[reaction.id] = (
                    reaction.lower_bound,
                    reaction.upper_bound,
                )
                reaction.bounds = (0, 0)
            try:
                # run fba
                result = fba(model)
                value = result.objective_value
                status = CuratorConstants.STATUS_OPTIMAL
            except Exception as e:
                logger.error(f"{e}")
                value = CuratorConstants.VALUE_INFEASIBLE
                status = CuratorConstants.STATUS_INFEASIBLE
            gene_status.append(status)
            gene_values.append(value)

            # restore bounds
            for rid, bounds in reaction_bounds.items():
                model.reactions.get_by_id(rid).bounds = bounds[:]

        return pd.DataFrame(
            {
                "model": self.model_path.name,
                "objective": self.objective_id,
                "gene": [gene.id for gene in model.genes],
                "status": gene_status,
                "value": gene_values,
            }
        )
Ejemplo n.º 14
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    def objective(self) -> pd.DataFrame:
        model = self.read_model()
        try:
            # fbc optimization
            result = fba(model)
            value = result.objective_value
            status = CuratorConstants.STATUS_OPTIMAL
        except Exception as e:
            logger.error(f"{e}")
            value = CuratorConstants.VALUE_INFEASIBLE
            status = CuratorConstants.STATUS_INFEASIBLE

        return pd.DataFrame(
            {
                "model": self.model_path.name,
                "objective": [self.objective_id],
                "status": [status],
                "value": [value],
            }
        )
Ejemplo n.º 15
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 def calculate_yield(model, source, product):
     try:
         flux_dist = fba(model, objective=product)
         return flux_dist[product.id] / abs(flux_dist[source.id])
     except OptimizationError:
         return 0.0
Ejemplo n.º 16
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def gimme(model,
          expression_profile=None,
          cutoff=None,
          objective=None,
          objective_dist=None,
          fraction_of_optimum=0.9,
          normalization=or2min_and2max,
          condition=None,
          not_measured_value=None,
          *args,
          **kwargs):
    """
    Gene Inactivity Moderated by Metabolism and Expression (GIMME)[1]

    Parameters
    ----------
    model: SolverBased Model
        A constraint based model
    expression_profile: ExpressionProfile
        An expression profile
    cutoff: float
        inactivity threshold
    objective: str or other cameo compatible objective
        The Minimal Required Functionalities (MRF)
    objective_dist: FluxDistributionResult
        A predetermined flux distribution for the objective can be provided (optional)
    fraction_of_optimum: float
        The fraction of the MRF
    normalization: function
        expression profile normalization function
    condition: str, int or None
        The condition from the expression profile. If None (default), the first condition on the profile will be used.
    normalization: function
        The normalization function to convert the gene expression profile into reaction expression profile (default: max)

    Returns
    -------
    GimmeResult

    References
    ----------
    .. [1] Becker, S. a and Palsson, B. O. (2008). Context-specific metabolic networks are consistent with experiments.
       PLoS Computational Biology, 4(5), e1000082. doi:10.1371/journal.pcbi.1000082
    """

    assert isinstance(model, SolverBasedModel)
    assert isinstance(expression_profile, ExpressionProfile)
    assert isinstance(fraction_of_optimum, numbers.Number)
    assert isinstance(cutoff, numbers.Number)

    objective = model.objective if objective is None else objective
    objective_dist = fba(
        model,
        objective=objective) if objective_dist is None else objective_dist

    assert isinstance(objective_dist, FluxDistributionResult)

    if objective.direction == 'max':
        fix_obj_constraint = model.solver.interface.Constraint(
            model.objective.expression,
            lb=fraction_of_optimum * objective_dist.objective_value,
            name="required metabolic functionalities")
    else:
        fix_obj_constraint = model.solver.interface.Constraint(
            model.objective.expression,
            ub=fraction_of_optimum * objective_dist.objective_value,
            name="required metabolic functionalities")
    objective_terms = list()

    condition = expression_profile.conditions[
        0] if condition is None else condition
    not_measured_value = cutoff if not_measured_value is None else not_measured_value

    reaction_profile = expression_profile.to_reaction_dict(
        condition, model, not_measured_value, normalization)
    coefficients = {
        r: cutoff - exp if cutoff > exp else 0
        for r, exp in six.iteritems(reaction_profile)
    }

    for rid, coefficient in six.iteritems(coefficients):
        reaction = model.reactions.get_by_id(rid)
        if coefficient > 0:
            objective_terms.append(
                coefficient *
                (reaction.forward_variable + reaction.reverse_variable))

    with TimeMachine() as tm:
        gimme_objective = model.solver.interface.Objective(
            Add(*objective_terms), direction="min")
        tm(do=partial(setattr, model, "objective", gimme_objective),
           undo=partial(setattr, model, "objective",
                        model.objective.expression))
        tm(do=partial(model.solver.add, fix_obj_constraint),
           undo=partial(model.solver.remove, [fix_obj_constraint]))
        solution = model.solve()
        return GimmeResult(solution.fluxes, solution.f, objective_dist.fluxes,
                           reaction_profile, cutoff)
Ejemplo n.º 17
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    def run(self,
            product=None,
            max_predictions=float("inf"),
            min_production=.1,
            timeout=None,
            callback=None,
            silent=False,
            allow_native_exchanges=False):
        """Run pathway prediction for a desired product.

        Parameters
        ----------
        product : Metabolite, str
            Metabolite or id or name of metabolite to find production pathways for.
        max_predictions : int, optional
            The maximum number of predictions to compute.
        min_production : float
            The minimum acceptable production flux to product.
        timeout : int
            The time limit [seconds] per attempted prediction.
        callback : function
            A function that takes a successfully predicted pathway.
        silent : bool
            If True will print the pathways and max flux values.
        allow_native_exchanges: bool
            If True, exchange reactions for native metabolites will be allowed.

        Returns
        -------
        PathwayPredictions
            The predicted pathways.
        """

        product = self._find_product(product)

        pathways = list()
        with TimeMachine() as tm, self.model:
            tm(do=partial(setattr, self.model.solver.configuration, 'timeout',
                          timeout),
               undo=partial(setattr, self.model.solver.configuration,
                            'timeout',
                            self.model.solver.configuration.timeout))
            try:
                product_reaction = self.model.reactions.get_by_id('DM_' +
                                                                  product.id)
            except KeyError:
                product_reaction = self.model.add_boundary(product,
                                                           type='demand')

            product_reaction.lower_bound = min_production
            counter = 1
            while counter <= max_predictions:
                logger.debug('Predicting pathway No. %d' % counter)
                try:
                    self.model.slim_optimize(error_value=None)
                except OptimizationError as e:
                    logger.error(
                        'No pathway could be predicted. Terminating pathway predictions.'
                    )
                    logger.error(e)
                    break

                vars_to_cut = list()
                for i, y_var_id in enumerate(self._y_vars_ids):
                    y_var = self.model.solver.variables[y_var_id]
                    if y_var.primal == 1.0:
                        vars_to_cut.append(y_var)
                logger.info(vars_to_cut)

                if len(vars_to_cut) == 0:
                    # no pathway found:
                    logger.info(
                        "It seems %s is a native product in model %s. "
                        "Let's see if we can find better heterologous pathways."
                        % (product, self.model))
                    # knockout adapter with native product
                    for adapter in self.adpater_reactions:
                        if product in adapter.metabolites:
                            logger.info(
                                'Knocking out adapter reaction %s containing native product.'
                                % adapter)
                            adapter.knock_out()
                    continue

                pathway = [
                    self.model.reactions.get_by_id(y_var.name[2:])
                    for y_var in vars_to_cut
                ]

                pathway_metabolites = set([
                    m for pathway_reaction in pathway
                    for m in pathway_reaction.metabolites
                ])
                logger.info('Pathway predicted: %s' % '\t'.join([
                    r.build_reaction_string(use_metabolite_names=True)
                    for r in pathway
                ]))
                pathway_metabolites.add(product)

                # Figure out adapter reactions to include
                adapters = [
                    adapter for adapter in self.adpater_reactions
                    if adapter.products[0] in pathway_metabolites
                ]

                # Figure out exchange reactions to include
                exchanges = [
                    exchange for exchange in self._exchanges
                    if abs(exchange.flux) > non_zero_flux_threshold
                    and exchange.id != product_reaction.id
                ]

                if allow_native_exchanges:
                    exchanges = [
                        exchange for exchange in exchanges
                        if list(exchange.metabolites)[0] in pathway_metabolites
                    ]

                pathway = PathwayResult(pathway, exchanges, adapters,
                                        product_reaction)
                if not silent:
                    util.display_pathway(pathway, counter)

                integer_cut = self.model.solver.interface.Constraint(
                    Add(*vars_to_cut),
                    name="integer_cut_" + str(counter),
                    ub=len(vars_to_cut) - 1)
                logger.debug('Adding integer cut.')
                tm(do=partial(self.model.solver.add, integer_cut),
                   undo=partial(self.model.solver.remove, integer_cut))

                # Test pathway in the original model
                with self.original_model:
                    pathway.apply(self.original_model)
                    try:
                        solution = fba(self.original_model,
                                       objective=pathway.product.id)
                    except OptimizationError as e:
                        logger.error(e)
                        logger.error(
                            "Addition of pathway {} made the model unsolvable. "
                            "Skipping pathway.".format(pathway))
                        continue
                    else:
                        if solution[
                                pathway.product.id] > non_zero_flux_threshold:
                            pathways.append(pathway)
                            if not silent:
                                print("Max flux: %.5f" %
                                      solution[pathway.product.id])
                        else:
                            logger.error(
                                "Pathway {} couldn't be verified. Production flux {}"
                                "is below requirement {}. Skipping pathway.".
                                format(pathway, solution[pathway.product.id],
                                       non_zero_flux_threshold))
                    finally:
                        counter += 1
                        if callback is not None:
                            callback(pathway)

            return PathwayPredictions(pathways)
Ejemplo n.º 18
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def gimme(
    model,
    expression_profile=None,
    cutoff=None,
    objective=None,
    objective_dist=None,
    fraction_of_optimum=0.9,
    normalization=or2min_and2max,
    condition=None,
    not_measured_value=None,
    *args,
    **kwargs
):
    """
    Gene Inactivity Moderated by Metabolism and Expression (GIMME)[1]

    Parameters
    ----------
    model: SolverBased Model
        A constraint based model
    expression_profile: ExpressionProfile
        An expression profile
    cutoff: float
        inactivity threshold
    objective: str or other cameo compatible objective
        The Minimal Required Functionalities (MRF)
    objective_dist: FluxDistributionResult
        A predetermined flux distribution for the objective can be provided (optional)
    fraction_of_optimum: float
        The fraction of the MRF
    normalization: function
        expression profile normalization function
    condition: str, int or None
        The condition from the expression profile. If None (default), the first condition on the profile will be used.
    normalization: function
        The normalization function to convert the gene expression profile into reaction expression profile (default: max)

    Returns
    -------
    GimmeResult

    References
    ----------
    .. [1] Becker, S. a and Palsson, B. O. (2008). Context-specific metabolic networks are consistent with experiments.
       PLoS Computational Biology, 4(5), e1000082. doi:10.1371/journal.pcbi.1000082
    """

    assert isinstance(model, SolverBasedModel)
    assert isinstance(expression_profile, ExpressionProfile)
    assert isinstance(fraction_of_optimum, numbers.Number)
    assert isinstance(cutoff, numbers.Number)

    objective = model.objective if objective is None else objective
    objective_dist = fba(model, objective) if objective_dist is None else objective_dist

    assert isinstance(objective_dist, FluxDistributionResult)

    if objective.direction == "max":
        fix_obj_constraint = model.solver.interface.Constraint(
            model.objective.expression,
            lb=fraction_of_optimum * objective_dist.objective_value,
            name="required metabolic functionalities",
        )
    else:
        fix_obj_constraint = model.solver.interface.Constraint(
            model.objective.expression,
            ub=fraction_of_optimum * objective_dist.objective_value,
            name="required metabolic functionalities",
        )
    objective_terms = list()

    condition = expression_profile.conditions[0] if condition is None else condition
    not_measured_value = cutoff if not_measured_value is None else not_measured_value

    reaction_profile = expression_profile.to_reaction_dict(condition, model, not_measured_value, normalization)
    coefficients = {r: cutoff - exp if cutoff > exp else 0 for r, exp in six.iteritems(reaction_profile)}

    for rid, coefficient in six.iteritems(coefficients):
        reaction = model.reactions.get_by_id(rid)
        if coefficient > 0:
            objective_terms.append(coefficient * (reaction.forward_variable + reaction.reverse_variable))

    with TimeMachine() as tm:
        gimme_objective = model.solver.interface.Objective(Add(*objective_terms), direction="min")
        tm(
            do=partial(setattr, model, "objective", gimme_objective),
            undo=partial(setattr, model, "objective", model.objective.expression),
        )
        tm(
            do=partial(model.solver._add_constraint, fix_obj_constraint),
            undo=partial(model.solver._remove_constraints, [fix_obj_constraint]),
        )
        solution = model.solve()
        return GimmeResult(solution.fluxes, solution.f, objective_dist.fluxes, reaction_profile, cutoff)
Ejemplo n.º 19
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 def calculate_yield(model, source, product):
     try:
         flux_dist = fba(model, objective=product)
         return flux_dist[product.id] / abs(flux_dist[source.id])
     except OptimizationError:
         return 0.0
Ejemplo n.º 20
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'''
Created on 4 Dec 2018

@author: mate

load in CD4 model, extract all proteins and save them to a new .csv
'''

from cameo import load_model, fba

model = load_model('models/CD4T1670.xml')
print(model.reactions)
new_solution = model.optimize()
fba_result = fba(model)
print(fba_result)
print(fba_result.data_frame)
print(len(fba_result.data_frame))
# print(model.reactions)

for reactionO in model.reactions:
    for reactionI in reactionO.genes:
        print(reactionI)

fba_result.display_on_map("RECON1.Carbohydrate metabolism")