def add_prot_pool_reaction(model: cobra.Model, id_addition: str,
p_total: float, p_measured: float,
unmeasured_protein_fraction: float, mean_saturation: float) -> cobra.Model:
"""Adds a protein pool reaction with the given parameters, in accordance with the GECKO paper.
The protein pool reaction gets the id 'ER_pool'+id_addition
Arguments
----------
* model: cobra.Model ~ The model to which the protein pool reaction shall be added :D
* id_addition: str ~ A string that may be added ad the end of the protein pool reaction's id.
* p_total: float ~ g/gDW of all proteins per 1 gDW cells
* p_measured: float ~ g/gDW of all proteins with measured concentrations.
* unmeasured_protein_fraction: float ~ The fraction of the meass of the unmeasured proteins
on the total protein mass per gDW cells
* mean_saturation: float ~ A fitted value of all unmeasured protein's mean saturation.
Output
----------
The given cobra model with a protein pool reaction :D
"""
# See suppl. data of GECKO paper, equation S28
pp_reaction = cobra.Reaction("ER_pool"+id_addition)
pp_reaction.name = "prot_pool reaction for unmeasured proteins"
pp_reaction.subsystem = "AutoPACMEN"
pp_reaction.lower_bound = 0
pp_reaction.upper_bound = (p_total - p_measured) * unmeasured_protein_fraction * mean_saturation
# The flux is in g/gDW
prot_pool_metabolite = cobra.Metabolite(
"prot_pool",
name="prot_pool pseudometabolite for unmeasured proteins",
compartment="AutoPACMEN")
pp_reaction.add_metabolites({prot_pool_metabolite: 1.0})
model.add_reactions([pp_reaction])
return model, prot_pool_metabolite
def test_model_history(tmp_path):
"""Testing reading and writing of ModelHistory."""
model = Model("test")
model._sbml = {
"creators": [{
"familyName": "Mustermann",
"givenName": "Max",
"organisation": "Muster University",
"email": "*****@*****.**",
}]
}
sbml_path = join(str(tmp_path), "test.xml")
with open(sbml_path, "w") as f_out:
write_sbml_model(model, f_out)
with open(sbml_path, "r") as f_in:
model2 = read_sbml_model(f_in)
assert "creators" in model2._sbml
assert len(model2._sbml["creators"]) is 1
c = model2._sbml["creators"][0]
assert c["familyName"] == "Mustermann"
assert c["givenName"] == "Max"
assert c["organisation"] == "Muster University"
assert c["email"] == "*****@*****.**"
def fva_prot_pool(model: cobra.Model,
pp_upper_bounds: List[float],
objective: str = "") -> None:
"""Performs an FVA for the given protein-constraint-enhanced model with the given protein pools.
Output
----------
Standard cobrapy FVA result summaries for each given protein pool.
Arguments
----------
* model: cobra.Model ~ The FVAed model as cobrapy Model instance
* pp_upper_bounds: List[float] ~ The list of upper protein pool bounds.
* objective: str = "" ~ If set, the objecive will be changed to the given term. Otherwise, the standard
objective is used.
"""
for pp_upper_bound in pp_upper_bounds:
with model:
if objective != "":
model.objective = objective
model.reactions.get_by_id(
"ER_pool_TG_").upper_bound = pp_upper_bound
solution = model.optimize()
print(
f"\sMOMENT-enhanced model, FVA solution for prot_pool upper bound of {pp_upper_bound}:"
)
model.summary(fva=1.0)
print(
abs(solution.fluxes.EX_glc__D_e) /
abs(solution.fluxes.EX_ac_e))
model.metabolites.prot_pool.summary()
def test_solve_mip(self):
solver = self.solver
if not hasattr(solver, "_SUPPORTS_MILP") or not solver._SUPPORTS_MILP:
self.skipTest("no milp support")
cobra_model = Model('MILP_implementation_test')
constraint = Metabolite("constraint")
constraint._bound = 2.5
x = Reaction("x")
x.lower_bound = 0.
x.objective_coefficient = 1.
x.add_metabolites({constraint: 2.5})
y = Reaction("y")
y.lower_bound = 0.
y.objective_coefficient = 1.
y.add_metabolites({constraint: 1.})
cobra_model.add_reactions([x, y])
float_sol = solver.solve(cobra_model)
# add an integer constraint
y.variable_kind = "integer"
int_sol = solver.solve(cobra_model)
self.assertAlmostEqual(float_sol.f, 2.5)
self.assertAlmostEqual(float_sol.x_dict["y"], 2.5)
self.assertEqual(int_sol.status, "optimal")
self.assertAlmostEqual(int_sol.f, 2.2)
self.assertAlmostEqual(int_sol.x_dict["y"], 2.0)
def test_single_reaction_deletion_linear_room(
room_model: Model, room_solution: Solution, all_solvers: List[str]
) -> None:
"""Test single reaction deletion using linear ROOM."""
room_model.solver = all_solvers
expected = pd.Series(
{
"v1": 10.0,
"v2": 5.0,
"v3": 0.0,
"v4": 5.0,
"v5": 5.0,
"v6": 0.0,
"b1": 10.0,
"b2": 5.0,
"b3": 5.0,
},
index=["v1", "v2", "v3", "v4", "v5", "v6", "b1", "b2", "b3"],
)
with room_model:
room_model.reactions.v6.knock_out()
add_room(
room_model,
solution=room_solution,
delta=0.0,
epsilon=0.0,
linear=True,
)
linear_room_sol = room_model.optimize()
assert np.allclose(linear_room_sol.fluxes, expected)
def test_fva_minimization(model: Model) -> None:
"""Test minimization using FVA."""
model.objective = model.reactions.EX_glc__D_e
model.objective_direction = "min"
solution = flux_variability_analysis(model, fraction_of_optimum=0.95)
assert solution.at["EX_glc__D_e", "minimum"] == -10.0
assert solution.at["EX_glc__D_e", "maximum"] == -9.5
def test_change_coefficient(self):
solver = self.solver
c = Metabolite("c")
c._bound = 6
x = Reaction("x")
x.lower_bound = 1.
y = Reaction("y")
y.lower_bound = 0.
x.add_metabolites({c: 1})
#y.add_metabolites({c: 1})
z = Reaction("z")
z.add_metabolites({c: 1})
z.objective_coefficient = 1
m = Model("test_model")
m.add_reactions([x, y, z])
# change an existing coefficient
lp = solver.create_problem(m)
solver.solve_problem(lp)
sol1 = solver.format_solution(lp, m)
solver.change_coefficient(lp, 0, 0, 2)
solver.solve_problem(lp)
sol2 = solver.format_solution(lp, m)
self.assertAlmostEqual(sol1.f, 5.0)
self.assertAlmostEqual(sol2.f, 4.0)
# change a new coefficient
z.objective_coefficient = 0.
y.objective_coefficient = 1.
lp = solver.create_problem(m)
solver.change_coefficient(lp, 0, 1, 2)
solver.solve_problem(lp)
solution = solver.format_solution(lp, m)
self.assertAlmostEqual(solution.x_dict["y"], 2.5)
def create_model_from_rxns(name, rxns_d5, objective_rxn_id):
model = Model(name)
for rxn_d4 in rxns_d5:
new_rxn = create_rxn(rxn_d4)
model.add_reactions([new_rxn])
model.objective = objective_rxn_id
return model
def test_inequality(self):
# The space enclosed by the constraints is a 2D triangle with
# vertexes as (3, 0), (1, 2), and (0, 1)
solver = self.solver
# c1 encodes y - x > 1 ==> y > x - 1
# c2 encodes y + x < 3 ==> y < 3 - x
c1 = Metabolite("c1")
c2 = Metabolite("c2")
x = Reaction("x")
x.lower_bound = 0
y = Reaction("y")
y.lower_bound = 0
x.add_metabolites({c1: -1, c2: 1})
y.add_metabolites({c1: 1, c2: 1})
c1._bound = 1
c1._constraint_sense = "G"
c2._bound = 3
c2._constraint_sense = "L"
m = Model()
m.add_reactions([x, y])
# test that optimal values are at the vertices
m.objective = "x"
self.assertAlmostEqual(solver.solve(m).f, 1.0)
self.assertAlmostEqual(solver.solve(m).x_dict["y"], 2.0)
m.objective = "y"
self.assertAlmostEqual(solver.solve(m).f, 3.0)
self.assertAlmostEqual(solver.solve(m, objective_sense="minimize").f,
1.0)
def from_cobra(self, model: cobra.Model, name: str):
"""Initialize from cobra model."""
# gather prots from by naming convention
super().__init__(model.id, name)
g_proteins = [
met for met in model.metabolites if met.id.startswith("prot_")
]
# gather prots from by SBML group
if model.groups.query("Protein"):
g_proteins += model.groups.Protein.members
g_proteins = set(g_proteins)
model.remove_metabolites(g_proteins)
self.add_metabolites(
[met for met in model.metabolites if met not in g_proteins])
self.add_reactions([
reac for reac in model.reactions if not reac.id.startswith("prot_")
])
self.add_proteins([Protein(prot) for prot in g_proteins])
# point every previous protein Metabolite to an actual Protein object
for reac in self.reactions:
reac._metabolites = {
met if met not in g_proteins else self.proteins.get_by_id(
met.id): val
for met, val in reac.metabolites.items()
}
self.__setstate__(self.__dict__)
self._populate_solver(self.reactions, self.metabolites, self.proteins)
def test_model_history(tmp_path):
"""Testing reading and writing of ModelHistory."""
model = Model("test")
model._sbml = {
"creators": [{
"familyName": "Mustermann",
"givenName": "Max",
"organisation": "Muster University",
"email": "*****@*****.**",
}]
}
sbml_path = join(str(tmp_path), "test.xml")
with open(sbml_path, "w") as f_out:
write_sbml_model(model, f_out)
with open(sbml_path, "r") as f_in:
model2 = read_sbml_model(f_in)
assert "creators" in model2._sbml
assert len(model2._sbml["creators"]) is 1
c = model2._sbml["creators"][0]
assert c["familyName"] == "Mustermann"
assert c["givenName"] == "Max"
assert c["organisation"] == "Muster University"
assert c["email"] == "*****@*****.**"
def test_solve_mip(self):
solver = self.solver
if not hasattr(solver, "_SUPPORTS_MILP") or not solver._SUPPORTS_MILP:
self.skipTest("no milp support")
cobra_model = Model('MILP_implementation_test')
constraint = Metabolite("constraint")
constraint._bound = 2.5
x = Reaction("x")
x.lower_bound = 0.
x.objective_coefficient = 1.
x.add_metabolites({constraint: 2.5})
y = Reaction("y")
y.lower_bound = 0.
y.objective_coefficient = 1.
y.add_metabolites({constraint: 1.})
cobra_model.add_reactions([x, y])
float_sol = solver.solve(cobra_model)
# add an integer constraint
y.variable_kind = "integer"
int_sol = solver.solve(cobra_model)
self.assertAlmostEqual(float_sol.f, 2.5)
self.assertAlmostEqual(float_sol.x_dict["y"], 2.5)
self.assertEqual(int_sol.status, "optimal")
self.assertAlmostEqual(int_sol.f, 2.2)
self.assertAlmostEqual(int_sol.x_dict["y"], 2.0)
def swap_from_generic(self,
targets: list,
components: list,
same_components=False,
progress_bar_processes_left=1):
"""
Swap compounds from a generic target and components. The algorithm acts as follows:
1st: Starts for identifying the reactions present in the requested biosynthetic pathway;
2nd: Creates a virtual model;
3rd: Calls the granulator to granulate the biosynthetic pathway;
:param list<str> targets: list of lipid targets
:param list<str> components: list of components
:param bool same_components: boolean for same or mix of components
:param int progress_bar_processes_left:
:return:
"""
targets_generic_ontology_id, components_ont_ids = \
self.transform_targets_and_components_into_boimmg_ids(targets,components)
self.__virtual_model = Model("virtual_model")
self.__add_hydrogen_to_virtual_model()
self.__virtual_model_mapper = ModelMapper(
self.__virtual_model, self.__compoundsAnnotationConfigs,
self.__compoundsIdConverter)
self.__virtual_compounds_revisor = CompoundsRevisor(
self.__virtual_model, self.__universal_model,
self.__compoundsAnnotationConfigs)
self.__virtual_compounds_revisor.set_model_mapper(
self.__virtual_model_mapper)
self.granulator.set_virtual_model(self.__virtual_model,
self.__virtual_model_mapper,
self.__virtual_compounds_revisor)
for target_generic_ontology_id in targets_generic_ontology_id:
biosynthesis_reactions = self.granulator.identify_biosynthesis_pathway(
target_generic_ontology_id)
self.__biosynthesis_reactions = deepcopy(biosynthesis_reactions)
self.__add_new_reactions_to_virtual_model(
self.__biosynthesis_reactions)
self.__model.remove_reactions(biosynthesis_reactions)
self.granulator.granulate(target_generic_ontology_id,
components_ont_ids, same_components,
progress_bar_processes_left)
self.generateISAreactions()
def fva_comparison(model_original: cobra.Model,
model_smoment: cobra.Model,
objective: str = "") -> None:
"""Compares the original model with the AutoPACMEN model using FVA for 100% of the objective value.
The results are printed in the console, and are using cobrapy's FVA summary function.
Arguments
----------
* model_original: cobra.Model ~ The original SBML model for which the FVA shall be performed.
* model_smoment: cobra.Model ~ The AutoPACMENed model for which an FVA shall be performed.
* objective: str = "" ~ An alternative objective for both models. Keep in mind that due to the separation
of reversible reactions in the sMOMENTed model, there may be differential reaction names for the raction
that you want to be the objective.
"""
# Set objective if given for the original model :D
if objective != "":
model_original.objective = objective
# Perform and print FVA for the original model :D
model_original.optimize()
print(
"Original model, FVA solution (for 100% of the maximal objective value):"
)
model_original.summary(fva=1.0)
# Set objective if given for the sMOMENTed model :D
if objective != "":
model_smoment.objective = objective
# Perform and print FVA for the sMOMENTed model :D
model_smoment.optimize()
print(
"\sMOMENT-enhanced model, FVA solution (for 100% of the maximal objective value):"
)
model_smoment.summary()
def opposing_model() -> Model:
"""Generate a toy model with opposing reversible reactions.
This toy model ensures that two opposing reversible reactions do not
appear as blocked.
"""
test_model = Model("opposing")
v1 = Reaction("v1")
v2 = Reaction("v2")
v3 = Reaction("v3")
v4 = Reaction("v4")
test_model.add_reactions([v1, v2, v3, v4])
v1.reaction = "-> 2 A"
v2.reaction = "A -> C" # Later made reversible via bounds.
v3.reaction = "D -> C" # Later made reversible via bounds.
v4.reaction = "D ->"
v1.bounds = 0.0, 3.0
v2.bounds = -3.0, 3.0
v3.bounds = -3.0, 3.0
v4.bounds = 0.0, 3.0
test_model.objective = v4
return test_model
def test_change_coefficient(self):
solver = self.solver
c = Metabolite("c")
c._bound = 6
x = Reaction("x")
x.lower_bound = 1.
y = Reaction("y")
y.lower_bound = 0.
x.add_metabolites({c: 1})
#y.add_metabolites({c: 1})
z = Reaction("z")
z.add_metabolites({c: 1})
z.objective_coefficient = 1
m = Model("test_model")
m.add_reactions([x, y, z])
# change an existing coefficient
lp = solver.create_problem(m)
solver.solve_problem(lp)
sol1 = solver.format_solution(lp, m)
solver.change_coefficient(lp, 0, 0, 2)
solver.solve_problem(lp)
sol2 = solver.format_solution(lp, m)
self.assertAlmostEqual(sol1.f, 5.0)
self.assertAlmostEqual(sol2.f, 4.0)
# change a new coefficient
z.objective_coefficient = 0.
y.objective_coefficient = 1.
lp = solver.create_problem(m)
solver.change_coefficient(lp, 0, 1, 2)
solver.solve_problem(lp)
solution = solver.format_solution(lp, m)
self.assertAlmostEqual(solution.x_dict["y"], 2.5)
def test_room_sanity(
model: Model, all_solvers: List[str], linear: bool, delta: float, eps: float
) -> None:
"""Test optimization criterion and optimality for ROOM."""
model.solver = all_solvers
sol = model.optimize()
with model:
model.reactions.PYK.knock_out()
knock_sol = model.optimize()
with model:
# let it calculate its own reference solution (pFBA)
add_room(model, linear=linear, delta=delta, epsilon=eps)
model.reactions.PYK.knock_out()
room_sol = model.optimize()
with model:
# use the more distant FBA reference
add_room(model, solution=sol, linear=linear, delta=delta, epsilon=eps)
model.reactions.PYK.knock_out()
room_sol_ref = model.optimize()
# The
flux_change = (sol.fluxes - knock_sol.fluxes).abs()
flux_change_room = (sol.fluxes - room_sol.fluxes).abs()
flux_change_room_ref = (sol.fluxes - room_sol_ref.fluxes).abs()
rxn_count_naive = (flux_change > delta * sol.fluxes.abs() + eps + 1e-6).sum()
rxn_count_room = (flux_change_room > delta * sol.fluxes.abs() + eps + 1e-6).sum()
rxn_count_room_ref = (
flux_change_room_ref > delta * sol.fluxes.abs() + eps + 1e-6
).sum()
# Expect the ROOM solution to have less changed reactions then a pFBA or FBA
assert rxn_count_room <= rxn_count_naive
assert rxn_count_room_ref <= rxn_count_naive
def test_linear_moma_sanity(model: Model, all_solvers: List[str]) -> None:
"""Test optimization criterion and optimality for linear MOMA."""
model.solver = all_solvers
sol = model.optimize()
with model:
model.reactions.PFK.knock_out()
knock_sol = model.optimize()
sabs = (knock_sol.fluxes - sol.fluxes).abs().sum()
with model:
add_moma(model, linear=True)
model.reactions.PFK.knock_out()
moma_sol = model.optimize()
moma_sabs = (moma_sol.fluxes - sol.fluxes).abs().sum()
# Use normal FBA as reference solution.
with model:
add_moma(model, solution=sol, linear=True)
model.reactions.PFK.knock_out()
moma_ref_sol = model.optimize()
moma_ref_sabs = (moma_ref_sol.fluxes - sol.fluxes).abs().sum()
assert np.allclose(moma_sol.objective_value, moma_sabs)
assert moma_sabs < sabs
assert np.isclose(moma_sol.objective_value, moma_ref_sol.objective_value)
assert np.isclose(moma_sabs, moma_ref_sabs)
with model:
add_moma(model, linear=True)
with pytest.raises(ValueError):
add_moma(model)
def test_moma_sanity(model: Model, qp_solvers: List[str]) -> None:
"""Test optimization criterion and optimality for MOMA."""
model.solver = qp_solvers
sol = model.optimize()
with model:
model.reactions.PFK.knock_out()
knock_sol = model.optimize()
ssq = (knock_sol.fluxes - sol.fluxes).pow(2).sum()
with model:
add_moma(model, linear=False)
model.reactions.PFK.knock_out()
moma_sol = model.optimize()
moma_ssq = (moma_sol.fluxes - sol.fluxes).pow(2).sum()
# Use normal FBA as reference solution.
with model:
add_moma(model, solution=sol, linear=False)
model.reactions.PFK.knock_out()
moma_ref_sol = model.optimize()
moma_ref_ssq = (moma_ref_sol.fluxes - sol.fluxes).pow(2).sum()
assert np.isclose(moma_sol.objective_value, moma_ssq)
assert moma_ssq < ssq
assert np.isclose(moma_sol.objective_value, moma_ref_sol.objective_value)
assert np.isclose(moma_ssq, moma_ref_ssq)
def minimized_shuffle(small_model):
model = small_model.copy()
chosen = sample(list(set(model.reactions) - set(model.exchanges)), 10)
new = Model("minimized_shuffle")
new.add_reactions(chosen)
LOGGER.debug("'%s' has %d metabolites, %d reactions, and %d genes.",
new.id, new.metabolites, new.reactions, new.genes)
return new
def gapfillfunc(model, database, runs):
""" This function gapfills the model using the growMatch algorithm that is built into cobrapy
Returns a dictionary which contains the pertinent information about the gapfilled model such as
the reactions added, the major ins and outs of the system and the objective value of the gapfilled
model.
This function calls on two other functions sort_and_deduplicate to assure the uniqueness of the solutions
and findInsAndOuts to find major ins and outs of the model when gapfilled when certain reactions
Args:
model: a model in SBML format
database: an external database database of reactions to be used for gapfilling
runs: integer number of iterations the gapfilling algorithm will run through
"""
# Read model from SBML file and create Universal model to add reactions to
func_model = create_cobra_model_from_sbml_file(model)
Universal = Model("Universal Reactions")
f = open(database, 'r')
next(f)
rxn_dict = {}
# Creates a dictionary of the reactions from the tab delimited database, storing their ID and the reaction string
for line in f:
rxn_items = line.split('\t')
rxn_dict[rxn_items[0]] = rxn_items[6], rxn_items[1]
# Adds the reactions from the above dictionary to the Universal model
for rxnName in rxn_dict.keys():
rxn = Reaction(rxnName)
Universal.add_reaction(rxn)
rxn.reaction = rxn_dict[rxnName][0]
rxn.name = rxn_dict[rxnName][1]
# Runs the growMatch algorithm filling gaps from the Universal model
result = flux_analysis.growMatch(func_model, Universal, iterations=runs)
resultShortened = sort_and_deduplicate(uniq(result))
rxns_added = {}
rxn_met_list = []
print resultShortened
for x in range(len(resultShortened)):
func_model_test = deepcopy(func_model)
# print func_model_test.optimize().f
for i in range(len(resultShortened[x])):
addID = resultShortened[x][i].id
rxn = Reaction(addID)
func_model_test.add_reaction(rxn)
rxn.reaction = resultShortened[x][i].reaction
rxn.reaction = re.sub('\+ dummy\S+', '', rxn.reaction)
rxn.name = resultShortened[x][i].name
mets = re.findall('cpd\d{5}_c0|cpd\d{5}_e0', rxn.reaction)
for met in mets:
y = func_model_test.metabolites.get_by_id(met)
rxn_met_list.append(y.name)
obj_value = func_model_test.optimize().f
fluxes = findInsAndOuts(func_model_test)
sorted_outs = fluxes[0]
sorted_ins = fluxes[1]
rxns_added[x] = resultShortened[x], obj_value, sorted_ins, sorted_outs, rxn_met_list
rxn_met_list = []
return rxns_added
def __init__(self, model, name):
"""
Very much model specific
"""
Model.__init__(self, model.copy(), name)
self._cons_queue = list()
self._var_queue = list()
def remove_reactions(self, reactions, remove_orphans=False):
# Remove the constraints and variables associated to these reactions
all_cons_subclasses = get_all_subclasses(ReactionConstraint)
all_var_subclasses = get_all_subclasses(ReactionVariable)
self._remove_associated_consvar(all_cons_subclasses,
all_var_subclasses, reactions)
Model.remove_reactions(self, reactions, remove_orphans)
def remove_metabolites(self, metabolite_list, destructive=False):
# Remove the constraints and variables associated to these reactions
all_cons_subclasses = get_all_subclasses(MetaboliteConstraint)
all_var_subclasses = get_all_subclasses(MetaboliteVariable)
self._remove_associated_consvar(all_cons_subclasses,
all_var_subclasses, metabolite_list)
Model.remove_metabolites(self, metabolite_list, destructive)
def tiny_toy_model():
tiny = Model("Toy Model")
m1 = Metabolite("M1")
d1 = Reaction("ex1")
d1.add_metabolites({m1: -1})
d1.upper_bound = 0
d1.lower_bound = -1000
tiny.add_reactions([d1])
tiny.objective = 'ex1'
return tiny
def repair(self):
"""
Updates references to variables and constraints
:return:
"""
# self.add_cons_vars([x.constraint for x in self._cons_dict.values()])
# self.add_cons_vars([x.variable for x in self._var_dict.values()])
Model.repair(self)
self.regenerate_constraints()
self.regenerate_variables()
def setUp(self):
self.model = Model("test model")
A = Metabolite("A")
r = Reaction("r")
r.add_metabolites({A: -1})
r.lower_bound = -1000
r.upper_bound = 1000
self.model.add_reaction(r)
convert_to_irreversible(self.model)
self.model.remove_reactions(["r"])
def restore_reaction_by_json(cobra_model: cobra.Model,
info: Dict[str, Any]) -> cobra.Reaction:
reaction = cobra.Reaction(id=info['cobra_id'],
name=info['name'],
subsystem=info['subsystem'],
lower_bound=info['lower_bound'],
upper_bound=info['upper_bound'])
cobra_model.add_reactions([reaction])
reaction.gene_reaction_rule = info['gene_reaction_rule']
return reaction
def tiny_toy_model():
tiny = Model("Toy Model")
m1 = Metabolite("M1")
d1 = Reaction("ex1")
d1.add_metabolites({m1: -1})
d1.upper_bound = 0
d1.lower_bound = -1000
tiny.add_reactions([d1])
tiny.objective = "ex1"
return tiny
def get_reference(mod, newR, delete_unbalanced, verbose=1):
from cobra import Model, Reaction, Metabolite
import pandas
import re
import os
dir = os.path.dirname(__file__)
seedmDB = pandas.read_csv(dir + "/../dat/seed_metabolites.tsv", sep="\t")
seedrDB = pandas.read_csv(dir + "/../dat/seed_reactions.tsv", sep="\t")
#refdb = seedrDB.loc[seedrDB['abbreviation'].isin(newR)] # vmh
refdb = seedrDB.loc[(seedrDB['id'].isin(newR)) &
(seedrDB['status'] == "OK"
)] # only choose reaction which have status okay
refmod = Model("reaction_database")
Rmod = [re.sub("_.*$", "", r.id) for r in mod.reactions]
print "Consider", len(refdb.index), "reactions"
Cold = 0
Calready = 0
for i, row in refdb.iterrows():
#rid = row["abbreviation"] # vmh
rid = row["id"]
if row["is_obsolete"] == 1: # do not add old reactions
Cold += 1
continue
#if rid in Rmod: # vmh
elif rid in Rmod:
Calready += 1
continue
r = Reaction(rid + "_c0") # default seed model have compartment tag
refmod.add_reaction(r)
#rstr = row["formula"] # vmh
rstr = row["equation"]
#rstr = row["code"]
rstr = rstr.replace("[0]", "_c0").replace("[1]", "_e0").replace(
"[3]", "_p0").replace("[2]", "_m0")
r.build_reaction_from_string(rstr, verbose=0)
#r.reaction = rstr
for m in refmod.metabolites:
if verbose == 2:
print m.id
mid = re.sub("_.*$", "", m.id)
hit = seedmDB.loc[seedmDB["id"] == mid]
m.name = hit["name"].values[0]
m.formula = hit["formula"].values[0]
m.charge = hit["charge"].values[0]
if verbose > 0:
print Calready, "reactions already in the model"
print Cold, "removed deprecated reactions"
refmod = repair_mass_balance(refmod, delete_unbalanced, verbose)
if verbose > 0:
print len(
refmod.reactions), "remaining reaction in reference database:",
return (refmod)
def model(request, solver):
if request.param == "empty":
model = Model(id_or_model=request.param, name=request.param)
elif request.param == "textbook":
model = read_sbml_model(join(dirname(__file__), "data",
"EcoliCore.xml.gz"))
else:
builder = getattr(request.module, "MODEL_REGISTRY")[request.param]
model = builder(Model(id_or_model=request.param, name=request.param))
model.solver = solver
return model
def test_remove_breaks(self):
model = Model("test model")
A = Metabolite("A")
r = Reaction("r")
r.add_metabolites({A: -1})
r.lower_bound = -1000
r.upper_bound = 1000
model.add_reaction(r)
convert_to_irreversible(model)
model.remove_reactions(["r"])
with pytest.raises(KeyError):
revert_to_reversible(model)
def createDict(file):
Universal = Model("Universal Reactions")
f = open('file', 'r')
rxn_dict = {}
for line in f:
rxn_items = line.split('\t')
rxn_dict[rxn_items[0]] = rxn_items[2]
for rxnName in rxn_dict.keys():
rxn = Reaction(rxnName)
Universal.add_reaction(rxn)
rxn.reaction = rxn_dict[rxnName]
return Universal
def test_quadratic(self):
solver = self.solver
if not hasattr(solver, "set_quadratic_objective"):
self.skipTest("no qp support")
c = Metabolite("c")
c._bound = 2
x = Reaction("x")
x.objective_coefficient = -0.5
x.lower_bound = 0.
y = Reaction("y")
y.objective_coefficient = -0.5
y.lower_bound = 0.
x.add_metabolites({c: 1})
y.add_metabolites({c: 1})
m = Model()
m.add_reactions([x, y])
lp = self.solver.create_problem(m)
quadratic_obj = scipy.sparse.eye(2) * 2
solver.set_quadratic_objective(lp, quadratic_obj)
solver.solve_problem(lp, objective_sense="minimize")
solution = solver.format_solution(lp, m)
self.assertEqual(solution.status, "optimal")
# Respecting linear objectives also makes the objective value 1.
self.assertAlmostEqual(solution.f, 1.)
self.assertAlmostEqual(solution.x_dict["y"], 1.)
self.assertAlmostEqual(solution.x_dict["y"], 1.)
# When the linear objectives are removed the objective value is 2.
solver.change_variable_objective(lp, 0, 0.)
solver.change_variable_objective(lp, 1, 0.)
solver.solve_problem(lp, objective_sense="minimize")
solution = solver.format_solution(lp, m)
self.assertEqual(solution.status, "optimal")
self.assertAlmostEqual(solution.f, 2.)
# test quadratic from solve function
solution = solver.solve(m, quadratic_component=quadratic_obj,
objective_sense="minimize")
self.assertEqual(solution.status, "optimal")
self.assertAlmostEqual(solution.f, 1.)
c._bound = 6
z = Reaction("z")
x.objective_coefficient = 0.
y.objective_coefficient = 0.
z.lower_bound = 0.
z.add_metabolites({c: 1})
m.add_reaction(z)
solution = solver.solve(m, quadratic_component=scipy.sparse.eye(3),
objective_sense="minimize")
# should be 12 not 24 because 1/2 (V^T Q V)
self.assertEqual(solution.status, "optimal")
self.assertAlmostEqual(solution.f, 6)
self.assertAlmostEqual(solution.x_dict["x"], 2, places=6)
self.assertAlmostEqual(solution.x_dict["y"], 2, places=6)
self.assertAlmostEqual(solution.x_dict["z"], 2, places=6)
def convert_to_cobra_model(the_network):
""" Take a generic NAMpy model and convert to
a COBRA model. The model is assumed to be monopartite.
You need a functional COBRApy for this.
Arguments:
the_network
kwargs:
flux_bounds
"""
continue_flag = True
try:
from cobra import Model, Reaction, Metabolite
except:
print 'This function requires a functional COBRApy, exiting ...'
if continue_flag:
__default_objective_coefficient = 0
if 'flux_bounds' in kwargs:
flux_bounds = kwargs['flux_bounds']
else:
flux_bounds = len(the_nodes)
metabolite_dict = {}
for the_node in the_network.nodetypes[0].nodes:
the_metabolite = Metabolite(the_node.id)
metabolite_dict.update({the_node.id: the_metabolite})
cobra_reaction_list = []
for the_edge in the_network.edges:
the_reaction = Reaction(the_edge.id)
cobra_reaction_list.append(the_reaction)
the_reaction.upper_bound = flux_bounds
the_reaction.lower_bound = -1 * flux_bounds
cobra_metabolites = {}
the_metabolite_id_1 = the_edge._nodes[0].id
the_metabolite_id_2 = the_edge._nodes[1].id
cobra_metabolites[metabolite_dict[the_metabolite_id_1]] = 1.
cobra_metabolites[metabolite_dict[the_metabolite_id_2]] = -1.
reaction.add_metabolites(cobra_metabolites)
reaction.objective_coefficient = __default_objective_coefficient
cobra_model = Model(model_id)
cobra_model.add_reactions(cobra_reaction_list)
return cobra_model
else:
return None
def Test():
model = Model('TEST')
nombre = "test_reaction"
reaction = Reaction(nombre)
reaction.name = '3 oxoacyl acyl carrier protein synthase n C140 '
reaction.subsystem = 'Cell Envelope Biosynthesis'
reaction.lower_bound = 0. # This is the default
reaction.upper_bound = 1000. # This is the default
reaction.add_metabolites({
Metabolite('malACP_c',
formula='C14H22N2O10PRS',
name='Malonyl-acyl-carrier-protein',
compartment='c'):
-1.0,
Metabolite('h_c', formula='H', name='H', compartment='c'):
-1.0,
Metabolite('ddcaACP_c',
formula='C23H43N2O8PRS',
name='Dodecanoyl-ACP-n-C120ACP',
compartment='c'):
-1.0,
Metabolite('co2_c', formula='CO2', name='CO2', compartment='c'):
1.0,
Metabolite('ACP_c',
formula='C11H21N2O7PRS',
name='acyl-carrier-protein',
compartment='c'):
1.0,
Metabolite('3omrsACP_c',
formula='C25H45N2O9PRS',
name='3-Oxotetradecanoyl-acyl-carrier-protein',
compartment='c'):
1.0
})
reaction.reaction
reaction.gene_reaction_rule = '( STM2378 or STM1197 )'
reaction.genes
model.add_reactions([reaction])
print('%i reaction' % len(model.reactions))
print('%i metabolites' % len(model.metabolites))
print('%i genes' % len(model.genes))
MostrarSistema()
model.objective = nombre
print(model.objective.expression)
print(model.objective.direction)
def setUp(self):
self.solver = solvers.solver_dict[self.solver_name]
self.model = create_test_model()
self.old_solution = 0.380008
self.infeasible_model = Model()
metabolite_1 = Metabolite("met1")
reaction_1 = Reaction("rxn1")
reaction_2 = Reaction("rxn2")
reaction_1.add_metabolites({metabolite_1: 1})
reaction_2.add_metabolites({metabolite_1: 1})
reaction_1.lower_bound = 1
reaction_2.upper_bound = 2
self.infeasible_model.add_reactions([reaction_1, reaction_2])
def cobra_model(self, name, reversible=True, bound=1000):
"""Constructs a cobra model for the reconstruction.
Args:
name (str): The name of the cobra model.
reversible (Optiona[bool]): Whether the returned model should
be reversible. Default is yes.
bound (Optional[float]): The default flux bound for the reactions.
Returns:
A cobra model containing the reconstruction. The original objective
will be conserved if it is still included in the model.
"""
new_mod = Model(name)
m = deepcopy(self.model)
for rid in self.conf:
r = m.reactions.get_by_id(rid)
if self.conf[rid] == 3 and "mock" not in r.notes:
if r not in new_mod.reactions:
r.upper_bound = bound
new_mod.add_reaction(r)
if "reflection" in r.notes:
rev = m.reactions.get_by_id(r.notes["reflection"])
if rev not in new_mod.reactions:
rev.upper_bound = bound
new_mod.add_reaction(rev)
if reversible:
revert_to_reversible(new_mod)
still_valid = True
for r in self.objective:
still_valid &= (self.conf[r.id] == 3)
if still_valid:
new_mod.change_objective(self.objective)
return new_mod
class TestCobraSolver(TestCase):
def setUp(self):
self.model = create_test_model()
initialize_growth_medium(self.model, "MgM")
self.old_solution = 0.320064
self.infeasible_model = Model()
metabolite_1 = Metabolite("met1")
# metabolite_2 = Metabolite("met2")
reaction_1 = Reaction("rxn1")
reaction_2 = Reaction("rxn2")
reaction_1.add_metabolites({metabolite_1: 1})
reaction_2.add_metabolites({metabolite_1: 1})
reaction_1.lower_bound = 1
reaction_2.upper_bound = 2
self.infeasible_model.add_reactions([reaction_1, reaction_2])
def test_gene_knockout_computation(self):
cobra_model = self.model
delete_model_genes = delete.delete_model_genes
get_removed = lambda m: {x.id for x in m._trimmed_reactions}
gene_list = ['STM1067', 'STM0227']
dependent_reactions = {'3HAD121', '3HAD160', '3HAD80', '3HAD140',
'3HAD180', '3HAD100', '3HAD181','3HAD120',
'3HAD60', '3HAD141', '3HAD161', 'T2DECAI',
'3HAD40'}
delete_model_genes(cobra_model, gene_list)
self.assertEqual(get_removed(cobra_model), dependent_reactions)
# cumulative
delete_model_genes(cobra_model, ["STM4221"],
cumulative_deletions=True)
dependent_reactions.add('PGI')
self.assertEqual(get_removed(cobra_model), dependent_reactions)
# non-cumulative
delete_model_genes(cobra_model, ["STM4221"],
cumulative_deletions=False)
self.assertEqual(get_removed(cobra_model), {'PGI'})
# make sure on reset that the bounds are correct
reset_bound = cobra_model.reactions.get_by_id("T2DECAI").upper_bound
self.assertEqual(reset_bound, 1000.)
# test computation when gene name is a subset of another
test_model = Model()
test_reaction_1 = Reaction("test1")
test_reaction_1.gene_reaction_rule = "eggs or (spam and eggspam)"
test_model.add_reaction(test_reaction_1)
delete.delete_model_genes(test_model, ["eggs"])
self.assertEqual(get_removed(test_model), set())
delete_model_genes(test_model, ["spam"], cumulative_deletions=True)
self.assertEqual(get_removed(test_model), {'test1'})
# test computation with nested boolean expression
delete.undelete_model_genes(test_model)
test_reaction_1.gene_reaction_rule = \
"g1 and g2 and (g3 or g4 or (g5 and g6))"
delete_model_genes(test_model, ["g3"], cumulative_deletions=False)
self.assertEqual(get_removed(test_model), set())
delete_model_genes(test_model, ["g1"], cumulative_deletions=False)
self.assertEqual(get_removed(test_model), {'test1'})
delete_model_genes(test_model, ["g5"], cumulative_deletions=False)
self.assertEqual(get_removed(test_model), set())
delete_model_genes(test_model, ["g3", "g4", "g5"],
cumulative_deletions=False)
self.assertEqual(get_removed(test_model), {'test1'})
def test_loopless(self):
try:
solver = get_solver_name(mip=True)
except:
self.skipTest("no MILP solver found")
test_model = Model()
test_model.add_metabolites(Metabolite("A"))
test_model.add_metabolites(Metabolite("B"))
test_model.add_metabolites(Metabolite("C"))
EX_A = Reaction("EX_A")
EX_A.add_metabolites({test_model.metabolites.A: 1})
DM_C = Reaction("DM_C")
DM_C.add_metabolites({test_model.metabolites.C: -1})
v1 = Reaction("v1")
v1.add_metabolites({test_model.metabolites.A: -1, test_model.metabolites.B: 1})
v2 = Reaction("v2")
v2.add_metabolites({test_model.metabolites.B: -1, test_model.metabolites.C: 1})
v3 = Reaction("v3")
v3.add_metabolites({test_model.metabolites.C: -1, test_model.metabolites.A: 1})
DM_C.objective_coefficient = 1
test_model.add_reactions([EX_A, DM_C, v1, v2, v3])
feasible_sol = construct_loopless_model(test_model).optimize()
v3.lower_bound = 1
infeasible_sol = construct_loopless_model(test_model).optimize()
self.assertEqual(feasible_sol.status, "optimal")
self.assertEqual(infeasible_sol.status, "infeasible")
def model():
A = Metabolite("A")
B = Metabolite("B")
C = Metabolite("C")
r1 = Reaction("r1")
r1.add_metabolites({A: -1, C: 1})
r2 = Reaction("r2")
r2.add_metabolites({B: -1, C: 1})
r3 = Reaction("EX_A")
r3.add_metabolites({A: 1})
r4 = Reaction("EX_B")
r4.add_metabolites({B: 1})
r5 = Reaction("EX_C")
r5.add_metabolites({C: -1})
mod = Model("test model")
mod.add_reactions([r1, r2, r3, r4, r5])
conf = {"r1": 1, "r2": -1, "EX_A": 1, "EX_B": 1, "EX_C": 1}
return (mod, conf)
def test_solve_mip(self):
solver = self.solver
cobra_model = Model('MILP_implementation_test')
constraint = Metabolite("constraint")
constraint._bound = 2.5
x = Reaction("x")
x.lower_bound = 0.
x.objective_coefficient = 1.
x.add_metabolites({constraint: 2.5})
y = Reaction("y")
y.lower_bound = 0.
y.objective_coefficient = 1.
y.add_metabolites({constraint: 1.})
cobra_model.add_reactions([x, y])
float_sol = solver.solve(cobra_model)
# add an integer constraint
y.variable_kind = "integer"
int_sol = solver.solve(cobra_model)
self.assertAlmostEqual(float_sol.f, 2.5)
self.assertAlmostEqual(float_sol.x_dict["y"], 2.5)
self.assertAlmostEqual(int_sol.f, 2.2)
self.assertAlmostEqual(int_sol.x_dict["y"], 2.0)
def setUp(self):
self.solver = solvers.solver_dict[self.solver_name]
self.model = create_test_model("textbook")
self.old_solution = 0.8739215
self.infeasible_model = Model()
metabolite_1 = Metabolite("met1")
reaction_1 = Reaction("rxn1")
reaction_2 = Reaction("rxn2")
reaction_1.add_metabolites({metabolite_1: 1})
reaction_2.add_metabolites({metabolite_1: 1})
reaction_1.lower_bound = 1
reaction_2.upper_bound = 2
self.infeasible_model.add_reactions([reaction_1, reaction_2])
def test_remove_genes(self):
m = Model("test")
m.add_reactions([Reaction("r" + str(i + 1)) for i in range(8)])
self.assertEqual(len(m.reactions), 8)
rxns = m.reactions
rxns.r1.gene_reaction_rule = "(a and b) or (c and a)"
rxns.r2.gene_reaction_rule = "(a and b and d and e)"
rxns.r3.gene_reaction_rule = "(a and b) or (b and c)"
rxns.r4.gene_reaction_rule = "(f and b) or (b and c)"
rxns.r5.gene_reaction_rule = "x"
rxns.r6.gene_reaction_rule = "y"
rxns.r7.gene_reaction_rule = "x or z"
rxns.r8.gene_reaction_rule = ""
self.assertIn("a", m.genes)
self.assertIn("x", m.genes)
delete.remove_genes(m, ["a"], remove_reactions=False)
self.assertNotIn("a", m.genes)
self.assertIn("x", m.genes)
self.assertEqual(rxns.r1.gene_reaction_rule, "")
self.assertEqual(rxns.r2.gene_reaction_rule, "")
self.assertEqual(rxns.r3.gene_reaction_rule, "b and c")
self.assertEqual(rxns.r4.gene_reaction_rule, "(f and b) or (b and c)")
self.assertEqual(rxns.r5.gene_reaction_rule, "x")
self.assertEqual(rxns.r6.gene_reaction_rule, "y")
self.assertEqual(rxns.r7.genes, {m.genes.x, m.genes.z})
self.assertEqual(rxns.r8.gene_reaction_rule, "")
delete.remove_genes(m, ["x"], remove_reactions=True)
self.assertEqual(len(m.reactions), 7)
self.assertNotIn("r5", m.reactions)
self.assertNotIn("x", m.genes)
self.assertEqual(rxns.r1.gene_reaction_rule, "")
self.assertEqual(rxns.r2.gene_reaction_rule, "")
self.assertEqual(rxns.r3.gene_reaction_rule, "b and c")
self.assertEqual(rxns.r4.gene_reaction_rule, "(f and b) or (b and c)")
self.assertEqual(rxns.r6.gene_reaction_rule, "y")
self.assertEqual(rxns.r7.gene_reaction_rule, "z")
self.assertEqual(rxns.r7.genes, {m.genes.z})
self.assertEqual(rxns.r8.gene_reaction_rule, "")
def setUp(self):
self.solver = solvers.solver_dict[self.solver_name]
self.model = create_test_model()
initialize_growth_medium(self.model, 'MgM')
self.old_solution = 0.320064
self.infeasible_model = Model()
metabolite_1 = Metabolite("met1")
reaction_1 = Reaction("rxn1")
reaction_2 = Reaction("rxn2")
reaction_1.add_metabolites({metabolite_1: 1})
reaction_2.add_metabolites({metabolite_1: 1})
reaction_1.lower_bound = 1
reaction_2.upper_bound = 2
self.infeasible_model.add_reactions([reaction_1, reaction_2])
def build_model():
m = Model("Blazier et al 2012")
m1_e = Metabolite("M1_e")
m1 = Metabolite("M1")
m2 = Metabolite("M2")
m3 = Metabolite("M3")
m4_e = Metabolite("M4_e")
m4 = Metabolite("M4")
m5 = Metabolite("M5")
r1 = Reaction("R1")
r1.add_metabolites({m1_e: -1, m1: 1})
r2 = Reaction("R2")
r2.add_metabolites({m1: -1, m2: 1})
r2.gene_reaction_rule = "Gene2"
r3 = Reaction("R3")
r3.add_metabolites({m2: -1, m3: 1})
r3.gene_reaction_rule = "Gene3"
r4 = Reaction("R4")
r4.add_metabolites({m3: -1})
r5 = Reaction("R5")
r5.add_metabolites({m4_e: -1, m4: 1})
r6 = Reaction("R6")
r6.add_metabolites({m4: -1, m5: 1})
r6.gene_reaction_rule = "Gene6"
r7 = Reaction("R7")
r7.add_metabolites({m5: -1, m2: 1})
r7.lower_bound = -r7.upper_bound
r7.gene_reaction_rule = "Gene7"
r8 = Reaction("R8")
r8.add_metabolites({m5: -1})
m.add_reactions([r1, r2, r3, r4, r5, r6, r7, r8])
EX_M1_e = m.add_boundary(m1_e)
EX_M1_e.lower_bound = -10
EX_M4_e = m.add_boundary(m4_e)
EX_M4_e.lower_bound = -10
m.objective = r4
return m
###Date Last Modified: May 25, 2016
###Contributors: Fahim, Zakary, Heba, Mike
# import these things
from cobra import Model, Reaction, Metabolite, Gene
import cobra.test
import os
import copy
from os.path import join
# create new model from sbml file
print("importing the existing the ecoli model...")
eco = cobra.io.sbml.create_cobra_model_from_sbml_file("/home/protoxpire0/Documents/igem/Gol_FBA/msb201165-s3.xml",old_sbml=False,legacy_metabolite=False,print_time=False,use_hyphens=False)
print("Creating new_model...")
new_model = Model('new_model')
print("Adding compartment 'a' for 'all'...")
new_model.compartments['a'] = 'all'
#Adding all metabolites from existing model removing duplications
print("Adding all metabolites from existing model removing duplications...")
for x in eco.metabolites:
dup = False
for y in new_model.metabolites:
if x.id[:-2] == y.id:
dup = True
break
if dup == False:
met = copy.deepcopy(x)
met.id = met.id[:-2]+'_a'
print(('Cones cost me $%1.2f to produce.'%(cone_production_cost)))
print(('I can sell popsicles for $%1.2f.'%(popsicle_selling_price)))
print(('Popsicles cost me $%1.2f to produce.'%(popsicle_production_cost)))
print(('My total budget was capped at $%1.2f today.'%(starting_budget)))
# problem is:
# max profit
# s.t.
# cone_production_cost*cone_production + popsidle_production_cost*popsicle_production <= starting_budget
# number of cones and popsicles has to be integer...
# first, we'll solve the continuous case just to make sure everything is
# working (it should only make cones)...then we'll tighten the constraints to
# integer... and it should make popsicles.
cobra_model = Model('MILP_implementation_test')
cone_out = Metabolite(id='cone_out', compartment='c')
cone_in = Metabolite(id='cone_in', compartment='c')
cone_consumed = Metabolite(id='cone_consumed', compartment='c')
popsicle_out = Metabolite(id='popsicle_out', compartment='c')
popsicle_in = Metabolite(id='popsicle_in', compartment='c')
popsicle_consumed = Metabolite(id='popsicle_consumed', compartment='c')
the_reactions = []
# SOURCE
Cone_source = Reaction(name='Cone_source')
temp_metabolite_dict = {cone_out: 1}
Cone_source.add_metabolites(temp_metabolite_dict)
the_reactions.append(Cone_source)
def create_modelFromReactionsAndMetabolitesTables(self,rxns_table_I,mets_table_I):
'''generate a cobra model from isotopomer_modelReactions and isotopomer_modelMetabolites tables'''
cobra_model = Model(rxns_table_I[0]['model_id']);
for rxn_cnt,rxn_row in enumerate(rxns_table_I):
#if rxn_row['rxn_id'] == 'HEX1':
# print 'check'
mets = {}
print(rxn_row['rxn_id'])
# parse the reactants
for rxn_met_cnt,rxn_met in enumerate(rxn_row['reactants_ids']):
for met_cnt,met_row in enumerate(mets_table_I):
if met_row['met_id']==rxn_met:# and met_row['balanced']:
compartment = met_row['compartment']
if not compartment:
met_id_tmp = met_row['met_id'].split('.')[0]
compartment = met_id_tmp.split('_')[-1];
met_tmp = Metabolite(met_row['met_id'],met_row['formula'],met_row['met_name'],compartment)
met_tmp.charge = met_row['charge']
# check for duplicate metabolites
met_keys = list(mets.keys());
met_keys_ids = {};
if met_keys:
for cnt,met in enumerate(met_keys):
met_keys_ids[met.id]=cnt;
if met_tmp.id in list(met_keys_ids.keys()):
mets[met_keys[met_keys_ids[met_tmp.id]]]-=1
else:
mets[met_tmp] = rxn_row['reactants_stoichiometry'][rxn_met_cnt];
break;
# parse the products
for rxn_met_cnt,rxn_met in enumerate(rxn_row['products_ids']):
for met_cnt,met_row in enumerate(mets_table_I):
if met_row['met_id']==rxn_met:# and met_row['balanced']:
compartment = met_row['compartment']
if not compartment:
met_id_tmp = met_row['met_id'].split('.')[0]
compartment = met_id_tmp.split('_')[-1];
met_tmp = Metabolite(met_row['met_id'],met_row['formula'],met_row['met_name'],compartment)
met_tmp.charge = met_row['charge']
# check for duplicate metabolites
met_keys = list(mets.keys());
met_keys_ids = {};
if met_keys:
for cnt,met in enumerate(met_keys):
met_keys_ids[met.id]=cnt;
if met_tmp.id in list(met_keys_ids.keys()):
mets[met_keys[met_keys_ids[met_tmp.id]]]+=1
else:
mets[met_tmp] = rxn_row['products_stoichiometry'][rxn_met_cnt];
break;
rxn = None;
rxn = Reaction(rxn_row['rxn_id']);
rxn.add_metabolites(mets);
rxn.lower_bound=rxn_row['lower_bound'];
rxn.upper_bound=rxn_row['upper_bound'];
rxn.subsystem=rxn_row['subsystem'];
rxn.gpr=rxn_row['gpr'];
rxn.objective_coefficient=rxn_row['objective_coefficient'];
cobra_model.add_reactions([rxn]);
cobra_model.repair();
return cobra_model
def solve_mip(self):
cone_selling_price = 7.0
cone_production_cost = 3.0
popsicle_selling_price = 2.0
popsicle_production_cost = 1.0
starting_budget = 100.0
cobra_model = Model("MILP_implementation_test")
cone_out = Metabolite(id="cone_out", compartment="c")
cone_in = Metabolite(id="cone_in", compartment="c")
cone_consumed = Metabolite(id="cone_consumed", compartment="c")
popsicle_out = Metabolite(id="popsicle_out", compartment="c")
popsicle_in = Metabolite(id="popsicle_in", compartment="c")
popsicle_consumed = Metabolite(id="popsicle_consumed", compartment="c")
the_reactions = []
# SOURCE
Cone_source = Reaction(name="Cone_source")
temp_metabolite_dict = {cone_out: 1}
Cone_source.add_metabolites(temp_metabolite_dict)
the_reactions.append(Cone_source)
Popsicle_source = Reaction(name="Popsicle_source")
temp_metabolite_dict = {popsicle_out: 1}
Popsicle_source.add_metabolites(temp_metabolite_dict)
the_reactions.append(Popsicle_source)
## PRODUCTION
Cone_production = Reaction(name="Cone_production")
temp_metabolite_dict = {cone_out: -1, cone_in: 1}
Cone_production.add_metabolites(temp_metabolite_dict)
the_reactions.append(Cone_production)
Popsicle_production = Reaction(name="Popsicle_production")
temp_metabolite_dict = {popsicle_out: -1, popsicle_in: 1}
Popsicle_production.add_metabolites(temp_metabolite_dict)
the_reactions.append(Popsicle_production)
## CONSUMPTION
Cone_consumption = Reaction(name="Cone_consumption")
temp_metabolite_dict = {cone_in: -1, cone_consumed: 1}
Cone_consumption.add_metabolites(temp_metabolite_dict)
the_reactions.append(Cone_consumption)
Popsicle_consumption = Reaction(name="Popsicle_consumption")
temp_metabolite_dict = {popsicle_in: -1, popsicle_consumed: 1}
Popsicle_consumption.add_metabolites(temp_metabolite_dict)
the_reactions.append(Popsicle_consumption)
# SINK
Cone_consumed_sink = Reaction(name="Cone_consumed_sink")
temp_metabolite_dict = {cone_consumed: -1}
Cone_consumed_sink.add_metabolites(temp_metabolite_dict)
the_reactions.append(Cone_consumed_sink)
Popsicle_consumed_sink = Reaction(name="Popsicle_consumed_sink")
temp_metabolite_dict = {popsicle_consumed: -1}
Popsicle_consumed_sink.add_metabolites(temp_metabolite_dict)
the_reactions.append(Popsicle_consumed_sink)
## add all reactions
cobra_model.add_reactions(the_reactions)
# set objective coefficients
Cone_consumption.objective_coefficient = cone_selling_price
Popsicle_consumption.objective_coefficient = popsicle_selling_price
Cone_production.objective_coefficient = -1 * cone_production_cost
Popsicle_production.objective_coefficient = -1 * popsicle_production_cost
# Make sure we produce whole cones
Cone_production.variable_kind = "integer"
Popsicle_production.variable_kind = "integer"
production_capacity_constraint = Metabolite(id="production_capacity_constraint")
production_capacity_constraint._constraint_sense = "L"
production_capacity_constraint._bound = starting_budget
Cone_production.add_metabolites({production_capacity_constraint: cone_production_cost})
Popsicle_production.add_metabolites({production_capacity_constraint: popsicle_production_cost})
cobra_model.optimize(solver=solver_name)
self.assertEqual(133, cobra_model.solution.f)
self.assertEqual(33, cobra_model.solution.x_dict["Cone_consumption"])
cone = Reaction("cone")
popsicle = Reaction("popsicle")
# constrainted to a budget
budget = Metabolite("budget")
budget._constraint_sense = "L"
budget._bound = starting_budget
cone.add_metabolites({budget: cone_production_cost})
popsicle.add_metabolites({budget: popsicle_production_cost})
# objective coefficient is the profit to be made from each unit
cone.objective_coefficient = cone_selling_price - cone_production_cost
popsicle.objective_coefficient = popsicle_selling_price - \
popsicle_production_cost
m = Model("lerman_ice_cream_co")
m.add_reactions((cone, popsicle))
m.optimize().x_dict
# Output:
# {'cone': 33.333333333333336, 'popsicle': 0.0}
# In reality, cones and popsicles can only be sold in integer amounts. We can
# use the variable kind attribute of a cobra.Reaction to enforce this.
cone.variable_kind = "integer"
popsicle.variable_kind = "integer"
m.optimize().x_dict
# Output:
# {'cone': 33.0, 'popsicle': 1.0}
from cobra.io.sbml import create_cobra_model_from_sbml_file
from cobra import Model, Reaction, flux_analysis
from copy import deepcopy
mattModel = create_cobra_model_from_sbml_file("2016_06_23_gapped_meoh_producing.xml")
Universal = Model("Universal Reactions")
f = open('2015_test_db_2.txt', 'r')
def uniq(lst):
last = object()
for item in lst:
if item == last:
continue
yield item
last = item
def sort_and_deduplicate(l):
return list(uniq(sorted(l, reverse=True)))
rxn_dict = {}
for line in f:
rxn_items = line.split('\t')
rxn_dict[rxn_items[0]] = rxn_items[2]
for rxnName in rxn_dict.keys():
rxn = Reaction(rxnName)
Universal.add_reaction(rxn)
rxn.reaction = rxn_dict[rxnName]
growthValue = []
its = 4
from cobra import Model, Reaction, Metabolite
cobra_model = Model('firstModel')
reaction = Reaction('3OAS140')
reaction.name = '3 oxoacyl carrier protein synthase n C140'
reaction.subsystem = 'Cell Envelope Biosynthesis'
ACP_c = Metabolite(
'ACP_c',
formula='C11H21N2O7PRS',
name='acyl-carrier-protein',
compartment='c')
omrsACP_c = Metabolite(
'3omrsACP_c',
formula='C25H45N2O9PRS',
name='3-Oxotetradecanoyl-acyl-carrier-protein',
compartment='c')
co2_c = Metabolite(
'co2_c',
formula='CO2',
name='CO2',
compartment='c')
malACP_c = Metabolite(
'malACP_c',
formula='C14H22N2O10PRS',
name='Malonyl-acyl-carrier-protein',
compartment='c')
h_c = Metabolite(
'h_c',
formula='H',
def test_gene_knockout_computation(self):
cobra_model = create_test_model()
# helper functions for running tests
delete_model_genes = delete.delete_model_genes
find_gene_knockout_reactions = delete.find_gene_knockout_reactions
def find_gene_knockout_reactions_fast(cobra_model, gene_list):
compiled_rules = delete.get_compiled_gene_reaction_rules(
cobra_model)
return find_gene_knockout_reactions(
cobra_model, gene_list,
compiled_gene_reaction_rules=compiled_rules)
def get_removed(m):
return {x.id for x in m._trimmed_reactions}
def test_computation(m, gene_ids, expected_reaction_ids):
genes = [m.genes.get_by_id(i) for i in gene_ids]
expected_reactions = {m.reactions.get_by_id(i)
for i in expected_reaction_ids}
removed1 = set(find_gene_knockout_reactions(m, genes))
removed2 = set(find_gene_knockout_reactions_fast(m, genes))
self.assertEqual(removed1, expected_reactions)
self.assertEqual(removed2, expected_reactions)
delete.delete_model_genes(m, gene_ids, cumulative_deletions=False)
self.assertEqual(get_removed(m), expected_reaction_ids)
delete.undelete_model_genes(m)
gene_list = ['STM1067', 'STM0227']
dependent_reactions = {'3HAD121', '3HAD160', '3HAD80', '3HAD140',
'3HAD180', '3HAD100', '3HAD181', '3HAD120',
'3HAD60', '3HAD141', '3HAD161', 'T2DECAI',
'3HAD40'}
test_computation(cobra_model, gene_list, dependent_reactions)
test_computation(cobra_model, ['STM4221'], {'PGI'})
test_computation(cobra_model, ['STM1746.S'], {'4PEPTabcpp'})
# test cumulative behavior
delete_model_genes(cobra_model, gene_list[:1])
delete_model_genes(cobra_model, gene_list[1:],
cumulative_deletions=True)
delete_model_genes(cobra_model, ["STM4221"],
cumulative_deletions=True)
dependent_reactions.add('PGI')
self.assertEqual(get_removed(cobra_model), dependent_reactions)
# non-cumulative following cumulative
delete_model_genes(cobra_model, ["STM4221"],
cumulative_deletions=False)
self.assertEqual(get_removed(cobra_model), {'PGI'})
# make sure on reset that the bounds are correct
reset_bound = cobra_model.reactions.get_by_id("T2DECAI").upper_bound
self.assertEqual(reset_bound, 1000.)
# test computation when gene name is a subset of another
test_model = Model()
test_reaction_1 = Reaction("test1")
test_reaction_1.gene_reaction_rule = "eggs or (spam and eggspam)"
test_model.add_reaction(test_reaction_1)
test_computation(test_model, ["eggs"], set())
test_computation(test_model, ["eggs", "spam"], {'test1'})
# test computation with nested boolean expression
test_reaction_1.gene_reaction_rule = \
"g1 and g2 and (g3 or g4 or (g5 and g6))"
test_computation(test_model, ["g3"], set())
test_computation(test_model, ["g1"], {'test1'})
test_computation(test_model, ["g5"], set())
test_computation(test_model, ["g3", "g4", "g5"], {'test1'})
# test computation when gene names are python expressions
test_reaction_1.gene_reaction_rule = "g1 and (for or in)"
test_computation(test_model, ["for", "in"], {'test1'})
test_computation(test_model, ["for"], set())
test_reaction_1.gene_reaction_rule = "g1 and g2 and g2.conjugate"
test_computation(test_model, ["g2"], {"test1"})
test_computation(test_model, ["g2.conjugate"], {"test1"})
test_reaction_1.gene_reaction_rule = "g1 and (try:' or 'except:1)"
test_computation(test_model, ["try:'"], set())
test_computation(test_model, ["try:'", "'except:1"], {"test1"})
def test_gapfilling(self):
try:
solver = get_solver_name(mip=True)
except:
self.skipTest("no MILP solver found")
m = Model()
m.add_metabolites(map(Metabolite, ["a", "b", "c"]))
r = Reaction("EX_A")
m.add_reaction(r)
r.add_metabolites({m.metabolites.a: 1})
r = Reaction("r1")
m.add_reaction(r)
r.add_metabolites({m.metabolites.b: -1, m.metabolites.c: 1})
r = Reaction("DM_C")
m.add_reaction(r)
r.add_metabolites({m.metabolites.c: -1})
r.objective_coefficient = 1
U = Model()
r = Reaction("a2b")
U.add_reaction(r)
r.build_reaction_from_string("a --> b", verbose=False)
r = Reaction("a2d")
U.add_reaction(r)
r.build_reaction_from_string("a --> d", verbose=False)
# GrowMatch
result = gapfilling.growMatch(m, U)[0]
self.assertEqual(len(result), 1)
self.assertEqual(result[0].id, "a2b")
# SMILEY
result = gapfilling.SMILEY(m, "b", U)[0]
self.assertEqual(len(result), 1)
self.assertEqual(result[0].id, "a2b")
# 2 rounds of GrowMatch with exchange reactions
result = gapfilling.growMatch(m, None, ex_rxns=True, iterations=2)
self.assertEqual(len(result), 2)
self.assertEqual(len(result[0]), 1)
self.assertEqual(len(result[1]), 1)
self.assertEqual({i[0].id for i in result}, {"SMILEY_EX_b", "SMILEY_EX_c"})
def build_model():
m = Model("Zur et al 2012")
m1 = Metabolite("M1")
m2 = Metabolite("M2")
m3 = Metabolite("M3")
m4 = Metabolite("M4")
m5 = Metabolite("M5")
m6 = Metabolite("M6")
m7 = Metabolite("M7")
m8 = Metabolite("M8")
m9 = Metabolite("M9")
m10 = Metabolite("M10")
r1 = Reaction("R1")
r1.add_metabolites({m3: 1})
r2 = Reaction("R2")
r2.add_metabolites({m1: 1})
r2.gene_reaction_rule = "G1 or G2"
r3 = Reaction("R3")
r3.add_metabolites({m2: 1})
r3.gene_reaction_rule = "G5"
r4 = Reaction("R4")
r4.add_metabolites({m1: -1, m10: 1})
r4.lower_bound = -r4.upper_bound
r5 = Reaction("R5")
r5.add_metabolites({m10: -1, m4: 1})
r5.lower_bound = -r5.upper_bound
r6 = Reaction("R6")
r6.add_metabolites({m1: -1, m4: 1})
r7 = Reaction("R7")
r7.add_metabolites({m1: -1, m2: -1, m5: 1, m6: 1})
r7.gene_reaction_rule = "G6"
r8 = Reaction("R8")
r8.add_metabolites({m3: -1, m4: -1, m7: 1, m8: 1})
r8.gene_reaction_rule = "G3"
r9 = Reaction("R9")
r9.add_metabolites({m5: -1})
r10 = Reaction("R10")
r10.add_metabolites({m6: -1, m9: 1})
r10.gene_reaction_rule = "G7"
r11 = Reaction("R11")
r11.add_metabolites({m7: -1})
r12 = Reaction("R12")
r12.add_metabolites({m8: -1})
r12.gene_reaction_rule = "G4"
r13 = Reaction("R13")
r13.add_metabolites({m9: -1})
m.add_reactions([r1, r2, r3, r4, r5, r6, r7, r8])
m.objective = r4
return m
# We need to use a solver that supports quadratic programming, such as gurobi
# or cplex. If a solver which supports quadratic programming is installed, this
# function will return its name.
print(solvers.get_solver_name(qp=True))
# Prints:
# gurobi
c = Metabolite("c")
c._bound = 2
x = Reaction("x")
y = Reaction("y")
x.add_metabolites({c: 1})
y.add_metabolites({c: 1})
m = Model()
m.add_reactions([x, y])
sol = m.optimize(quadratic_component=Q, objective_sense="minimize")
sol.x_dict
# Output:
# {'x': 1.0, 'y': 1.0}
# Suppose we change the problem to have a mixed linear and quadratic objective.
#
# > **min** $\frac{1}{2}\left(x^2 + y^2 \right) - y$
#
# > *subject to*
#
# > $x + y = 2$
#
# > $x \ge 0$