def test_solve_mip(self, solver_test):
solver, old_solution, infeasible_model = solver_test
if not hasattr(solver, "_SUPPORTS_MILP") or not solver._SUPPORTS_MILP:
pytest.skip("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)
assert abs(float_sol.f - 2.5) < 10 ** -5
assert abs(float_sol.x_dict["y"] - 2.5) < 10 ** -5
assert int_sol.status == "optimal"
assert abs(int_sol.f - 2.2) < 10 ** -3
assert abs(int_sol.x_dict["y"] - 2.0) < 10 ** -3
def test_iadd(model: Model) -> None:
"""Test in-place addition of reaction."""
PGI = model.reactions.PGI
EX_h2o = model.reactions.EX_h2o_e
original_PGI_gpr = PGI.gene_reaction_rule
PGI += EX_h2o
assert PGI.gene_reaction_rule == original_PGI_gpr
assert PGI.metabolites[model.metabolites.h2o_e] == -1.0
# Original should not change
assert EX_h2o.gene_reaction_rule == ""
assert EX_h2o.metabolites[model.metabolites.h2o_e] == -1.0
# Add a reaction not in the model
new_reaction = Reaction("test")
new_reaction.add_metabolites({Metabolite("A"): -1, Metabolite("B"): 1})
PGI += new_reaction
assert PGI.gene_reaction_rule == original_PGI_gpr
assert len(PGI.gene_reaction_rule) == 5
# And vice versa
new_reaction += PGI
assert len(new_reaction.metabolites) == 5 # not
assert len(new_reaction.genes) == 1
assert new_reaction.gene_reaction_rule == original_PGI_gpr
# Combine two GPRs
model.reactions.ACKr += model.reactions.ACONTa
expected_rule = "(b2296 or b3115 or b1849) and (b0118 or b1276)"
assert model.reactions.ACKr.gene_reaction_rule == expected_rule
assert len(model.reactions.ACKr.genes) == 5
def construct_geometric_fba_model():
test_model = Model('geometric_fba_paper_model')
test_model.add_metabolites(Metabolite('A'))
test_model.add_metabolites(Metabolite('B'))
v1 = Reaction('v1', upper_bound=1.0)
v1.add_metabolites({test_model.metabolites.A: 1.0})
v2 = Reaction('v2', lower_bound=-1000.0)
v2.add_metabolites({
test_model.metabolites.A: -1.0,
test_model.metabolites.B: 1.0
})
v3 = Reaction('v3', lower_bound=-1000.0)
v3.add_metabolites({
test_model.metabolites.A: -1.0,
test_model.metabolites.B: 1.0
})
v4 = Reaction('v4', lower_bound=-1000.0)
v4.add_metabolites({
test_model.metabolites.A: -1.0,
test_model.metabolites.B: 1.0
})
v5 = Reaction('v5')
v5.add_metabolites({
test_model.metabolites.A: 0.0,
test_model.metabolites.B: -1.0
})
test_model.add_reactions([v1, v2, v3, v4, v5])
test_model.objective = 'v5'
return test_model
def test_add_reaction_context(self, model):
old_reaction_count = len(model.reactions)
old_metabolite_count = len(model.metabolites)
dummy_metabolite_1 = Metabolite("test_foo_1")
dummy_metabolite_2 = Metabolite("test_foo_2")
actual_metabolite = model.metabolites[0]
copy_metabolite = model.metabolites[1].copy()
dummy_reaction = Reaction("test_foo_reaction")
dummy_reaction.add_metabolites({
dummy_metabolite_1: -1,
dummy_metabolite_2: 1,
copy_metabolite: -2,
actual_metabolite: 1
})
dummy_reaction.gene_reaction_rule = 'dummy_gene'
with model:
model.add_reaction(dummy_reaction)
assert model.reactions.get_by_id(dummy_reaction.id) == \
dummy_reaction
assert len(model.reactions) == old_reaction_count + 1
assert len(model.metabolites) == old_metabolite_count + 2
assert dummy_metabolite_1._model == model
assert 'dummy_gene' in model.genes
assert len(model.reactions) == old_reaction_count
assert len(model.metabolites) == old_metabolite_count
with pytest.raises(KeyError):
model.reactions.get_by_id(dummy_reaction.id)
assert dummy_metabolite_1._model is None
assert 'dummy_gene' not in model.genes
def test_iadd(self, model):
PGI = model.reactions.PGI
EX_h2o = model.reactions.EX_h2o_e
original_PGI_gpr = PGI.gene_reaction_rule
PGI += EX_h2o
assert PGI.gene_reaction_rule == original_PGI_gpr
assert PGI.metabolites[model.metabolites.h2o_e] == -1.0
# original should not have changed
assert EX_h2o.gene_reaction_rule == ''
assert EX_h2o.metabolites[model.metabolites.h2o_e] == -1.0
# what about adding a reaction not in the model
new_reaction = Reaction("test")
new_reaction.add_metabolites({Metabolite("A"): -1, Metabolite("B"): 1})
PGI += new_reaction
assert PGI.gene_reaction_rule == original_PGI_gpr
assert len(PGI.gene_reaction_rule) == 5
# and vice versa
new_reaction += PGI
assert len(new_reaction.metabolites) == 5 # not
assert len(new_reaction.genes) == 1
assert new_reaction.gene_reaction_rule == original_PGI_gpr
# what about combining 2 gpr's
model.reactions.ACKr += model.reactions.ACONTa
expected_rule = '(b2296 or b3115 or b1849) and (b0118 or b1276)'
assert model.reactions.ACKr.gene_reaction_rule == expected_rule
assert len(model.reactions.ACKr.genes) == 5
def test_get_yield_not_working_if_input_formula_missing(self):
model = Model("test")
met1 = Metabolite(id="S7P")
met2 = Metabolite(id="T3P1", formula="C3H7O6P")
met3 = Metabolite(id="E4P", formula="C4H9O7P")
met4 = Metabolite(id="F6P", formula="C6H13O9P")
model.add_metabolites((met1, met2, met3, met4))
react1 = Reaction(id="r1", name="Transaldolase")
react1.add_metabolites({met1: -1, met2: -1, met3: 1, met4: 1})
react2 = Reaction(id="r2")
react2.add_metabolites({met1: -1})
react3 = Reaction(id="r3")
react3.add_metabolites({met2: -1})
react4 = Reaction(id="r4")
react4.add_metabolites({met3: -1})
react5 = Reaction(id="r5")
react5.add_metabolites({met4: -1})
model.add_reactions((react1, react2, react3, react4, react5))
fluxes = {
react1.id: 1,
react2.id: -1,
react3.id: -1,
react4.id: 1,
react5.id: 1
}
status, _ = get_yields(fluxes, model)
assert status is False
def test_add_reactions(self, model):
r1 = Reaction('r1')
r1.add_metabolites({Metabolite('A'): -1, Metabolite('B'): 1})
r1.lower_bound, r1.upper_bound = -999999., 999999.
r2 = Reaction('r2')
r2.add_metabolites({
Metabolite('A'): -1,
Metabolite('C'): 1,
Metabolite('D'): 1
})
r2.lower_bound, r2.upper_bound = 0., 999999.
model.add_reactions([r1, r2])
r2.objective_coefficient = 3.
assert r2.objective_coefficient == 3.
assert model.reactions[-2] == r1
assert model.reactions[-1] == r2
assert isinstance(model.reactions[-2].reverse_variable,
model.problem.Variable)
coefficients_dict = model.objective.expression. \
as_coefficients_dict()
biomass_r = model.reactions.get_by_id('Biomass_Ecoli_core')
assert coefficients_dict[biomass_r.forward_variable] == 1.
assert coefficients_dict[biomass_r.reverse_variable] == -1.
assert coefficients_dict[model.reactions.r2.forward_variable] == 3.
assert coefficients_dict[model.reactions.r2.reverse_variable] == -3.
def construct_ll_test_model():
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
})
test_model.add_reactions([EX_A, DM_C, v1, v2, v3])
DM_C.objective_coefficient = 1
return test_model
def test_assess(self, model, solver):
with model:
assert assess(model, model.reactions.GLCpts, solver=solver) is True
pyr = model.metabolites.pyr_c
a = Metabolite('a')
b = Metabolite('b')
model.add_metabolites([a, b])
pyr_a2b = Reaction('pyr_a2b')
pyr_a2b.add_metabolites({pyr: -1, a: -1, b: 1})
model.add_reactions([pyr_a2b])
res = assess(model, pyr_a2b, 0.01, solver=solver)
expected = {
'precursors': {
a: {
'required': 0.01,
'produced': 0.0
}
},
'products': {
b: {
'required': 0.01,
'capacity': 0.0
}
}
}
assert res == expected
def test_change_coefficient(self, solver_test):
solver, old_solution, infeasible_model = solver_test
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})
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)
assert sol1.status == "optimal"
solver.change_coefficient(lp, 0, 0, 2)
solver.solve_problem(lp)
sol2 = solver.format_solution(lp, m)
assert sol2.status == "optimal"
assert abs(sol1.f - 5.0) < 10 ** -3
assert abs(sol2.f - 4.0) < 10 ** -3
# 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)
assert solution.status == "optimal"
assert abs(solution.x_dict["y"] - 2.5) < 10 ** -3
def test_add_reactions_single_existing(model):
rxn = model.reactions[0]
r1 = Reaction(rxn.id)
r1.add_metabolites({Metabolite("A"): -1, Metabolite("B"): 1})
r1.lower_bound, r1.upper_bound = -999999.0, 999999.0
model.add_reactions([r1])
assert rxn in model.reactions
assert r1 is not model.reactions.get_by_id(rxn.id)
def test_bad_exchange(model: Model) -> None:
"""Test bad exchange reaction identification."""
with pytest.raises(ValueError):
m = Metabolite("baddy", compartment="nonsense")
model.add_boundary(m, type="exchange")
m = Metabolite("goody", compartment="e")
rxn = model.add_boundary(m, type="exchange")
assert isinstance(rxn, Reaction)
def test_canonical_form(self, model):
# add G constraint to test
g_constr = Metabolite("SUCCt2_2__test_G_constraint")
g_constr._constraint_sense = "G"
g_constr._bound = 5.0
model.reactions.get_by_id("SUCCt2_2").add_metabolites({g_constr: 1})
assert abs(model.optimize("maximize").f - 0.855) < 0.001
# convert to canonical form
model = canonical_form(model)
assert abs(model.optimize("maximize").f - 0.855) < 10 ** -3
def test__normalize_pseudoreaction_atpm():
reaction = Reaction('notATPM')
reaction.add_metabolites({Metabolite('atp_c'): -1,
Metabolite('h2o_c'): -1,
Metabolite('pi_c'): 1,
Metabolite('h_c'): 1,
Metabolite('adp_c'): 1})
_normalize_pseudoreaction(reaction)
assert reaction.id == 'ATPM'
assert reaction.subsystem == 'Biomass and maintenance functions'
def test_canonical_form(self, model):
# add G constraint to test
g_constr = Metabolite("SUCCt2_2__test_G_constraint")
g_constr._constraint_sense = "G"
g_constr._bound = 5.0
model.reactions.get_by_id("SUCCt2_2").add_metabolites({g_constr: 1})
assert abs(model.optimize("maximize").f - 0.855) < 0.001
# convert to canonical form
model = canonical_form(model)
assert abs(model.optimize("maximize").f - 0.855) < 10**-3
def test__normalize_pseudoreaction_atpm_has_gpr():
reaction = Reaction('NPT1')
reaction.add_metabolites({Metabolite('atp_c'): -1,
Metabolite('h2o_c'): -1,
Metabolite('pi_c'): 1,
Metabolite('h_c'): 1,
Metabolite('adp_c'): 1})
reaction.gene_reaction_rule = 'b1779'
_normalize_pseudoreaction(reaction)
# should not change
assert reaction.id == 'NPT1'
def test_canonical_form(self):
model = create_test_model("textbook")
# add G constraint to test
g_constr = Metabolite("SUCCt2_2__test_G_constraint")
g_constr._constraint_sense = "G"
g_constr._bound = 5.0
model.reactions.get_by_id("SUCCt2_2").add_metabolites({g_constr: 1})
self.assertAlmostEqual(model.optimize("maximize").f, 0.855, places=3)
# convert to canonical form
model = canonical_form(model)
self.assertAlmostEqual(model.optimize("maximize").f, 0.855, places=3)
def test_set_id(self, solved_model):
solution, model = solved_model
met = Metabolite("test")
with pytest.raises(TypeError):
setattr(met, 'id', 1)
model.add_metabolites([met])
with pytest.raises(ValueError):
setattr(met, "id", 'g6p_c')
met.id = "test2"
assert "test2" in model.metabolites
assert "test" not in model.metabolites
def test_set_id(self, solved_model):
solution, model = solved_model
met = Metabolite("test")
with pytest.raises(TypeError):
setattr(met, 'id', 1)
model.add_metabolites([met])
with pytest.raises(ValueError):
setattr(met, "id", 'g6p_c')
met.id = "test2"
assert "test2" in model.metabolites
assert "test" not in model.metabolites
def test_compartments(self, model):
assert set(model.compartments) == {"c", "e"}
model = Model("test", "test")
met_c = Metabolite("a_c", compartment="c")
met_e = Metabolite("a_e", compartment="e")
rxn = Reaction("foo")
rxn.add_metabolites({met_e: -1, met_c: 1})
model.add_reactions([rxn])
assert model.compartments == {'c': '', 'e': ''}
model.compartments = {'c': 'cytosol'}
assert model.compartments == {'c': 'cytosol', 'e': ''}
def test_canonical_form(self):
model = create_test_model("textbook")
# add G constraint to test
g_constr = Metabolite("SUCCt2_2__test_G_constraint")
g_constr._constraint_sense = "G"
g_constr._bound = 5.0
model.reactions.get_by_id("SUCCt2_2").add_metabolites({g_constr: 1})
self.assertAlmostEqual(model.optimize("maximize").f, 0.855, places=3)
# convert to canonical form
model = canonical_form(model)
self.assertAlmostEqual(model.optimize("maximize").f, 0.855, places=3)
def test_get_yield(self):
model = Model("test")
met1 = Metabolite(id="S7P", formula="C7H15O10P")
met2 = Metabolite(id="T3P1", formula="C3H7O6P")
met3 = Metabolite(id="E4P", formula="C4H9O7P")
met4 = Metabolite(id="F6P", formula="C6H13O9P")
model.add_metabolites((met1, met2, met3, met4))
react1 = Reaction(id="r1", name="Transaldolase")
react1.add_metabolites({met1: -1, met2: -1, met3: 1, met4: 1})
react2 = Reaction(id="r2")
react2.add_metabolites({met1: -1})
react3 = Reaction(id="r3")
react3.add_metabolites({met2: -1})
react4 = Reaction(id="r4")
react4.add_metabolites({met3: -1})
react5 = Reaction(id="r5")
react5.add_metabolites({met4: -1})
model.add_reactions((react1, react2, react3, react4, react5))
fluxes = {
react1.id: 1,
react2.id: -1,
react3.id: -1,
react4.id: 1,
react5.id: 1
}
status, yields = get_yields(fluxes, model)
assert status is True
assert yields == {
"C": {
met3: 0.4,
met4: 0.6
},
"H": {
met3: 9 / 22,
met4: 13 / 22
},
"O": {
met3: 7 / 16,
met4: 9 / 16
},
"P": {
met3: 0.5,
met4: 0.5
}
}
def test_add_reactions_duplicate(model):
rxn = model.reactions[0]
r1 = Reaction('r1')
r1.add_metabolites({Metabolite('A'): -1, Metabolite('B'): 1})
r1.lower_bound, r1.upper_bound = -999999., 999999.
r2 = Reaction(rxn.id)
r2.add_metabolites(
{Metabolite('A'): -1, Metabolite('C'): 1, Metabolite('D'): 1})
model.add_reactions([r1, r2])
assert r1 in model.reactions
assert rxn in model.reactions
assert r2 is not model.reactions.get_by_id(rxn.id)
def test_quadratic(self, solver_test):
solver, old_solution, infeasible_model = solver_test
if not hasattr(solver, "set_quadratic_objective"):
pytest.skip("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 = 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)
assert solution.status == "optimal"
# Respecting linear objectives also makes the objective value 1.
assert abs(solution.f - 1.) < 10 ** -3
assert abs(solution.x_dict["y"] - 1.) < 10 ** -3
assert abs(solution.x_dict["y"] - 1.) < 10 ** -3
# 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)
assert solution.status == "optimal"
assert abs(solution.f - 2.) < 10 ** -3
# test quadratic from solve function
solution = solver.solve(m, quadratic_component=quadratic_obj,
objective_sense="minimize")
assert solution.status == "optimal"
assert abs(solution.f - 1.) < 10 ** -3
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)
assert solution.status == "optimal"
assert abs(solution.f - 6) < 10 ** -3
assert abs(solution.x_dict["x"] - 2) < 10 ** -6
assert abs(solution.x_dict["y"] - 2) < 10 ** -6
assert abs(solution.x_dict["z"] - 2) < 10 ** -6
def construct_loopless_model(cobra_model):
"""Construct a loopless model.
This adds MILP constraints to prevent flux from proceeding in a loop, as
done in http://dx.doi.org/10.1016/j.bpj.2010.12.3707
Please see the documentation for an explanation of the algorithm.
This must be solved with an MILP capable solver.
"""
# copy the model and make it irreversible
model = cobra_model.copy()
convert_to_irreversible(model)
max_ub = max(model.reactions.list_attr("upper_bound"))
# a dict for storing S^T
thermo_stoic = {"thermo_var_" + metabolite.id: {}
for metabolite in model.metabolites}
# Slice operator is so that we don't get newly added metabolites
original_metabolites = model.metabolites[:]
for reaction in model.reactions[:]:
# Boundary reactions are not subjected to these constraints
if len(reaction._metabolites) == 1:
continue
# populate the S^T dict
bound_id = "thermo_bound_" + reaction.id
for met, stoic in iteritems(reaction._metabolites):
thermo_stoic["thermo_var_" + met.id][bound_id] = stoic
# I * 1000 > v --> I * 1000 - v > 0
reaction_ind = Reaction(reaction.id + "_indicator")
reaction_ind.variable_kind = "integer"
reaction_ind.upper_bound = 1
reaction_ub = Metabolite(reaction.id + "_ind_ub")
reaction_ub._constraint_sense = "G"
reaction.add_metabolites({reaction_ub: -1})
reaction_ind.add_metabolites({reaction_ub: max_ub})
# This adds a compensating term for 0 flux reactions, so we get
# S^T x - (1 - I) * 1001 < -1 which becomes
# S^T x < 1000 for 0 flux reactions and
# S^T x < -1 for reactions with nonzero flux.
reaction_bound = Metabolite(bound_id)
reaction_bound._constraint_sense = "L"
reaction_bound._bound = max_ub
reaction_ind.add_metabolites({reaction_bound: max_ub + 1})
model.add_reaction(reaction_ind)
for metabolite in original_metabolites:
metabolite_var = Reaction("thermo_var_" + metabolite.id)
metabolite_var.lower_bound = -max_ub
model.add_reaction(metabolite_var)
metabolite_var.add_metabolites(
{model.metabolites.get_by_id(k): v
for k, v in iteritems(thermo_stoic[metabolite_var.id])})
return model
def test__normalize_pseudoreaction_atpm_reversed():
reaction = Reaction('notATPM')
reaction.add_metabolites({Metabolite('atp_c'): 1,
Metabolite('h2o_c'): 1,
Metabolite('pi_c'): -1,
Metabolite('h_c'): -1,
Metabolite('adp_c'): -1})
reaction.lower_bound = -50
reaction.upper_bound = 100
_normalize_pseudoreaction(reaction)
assert reaction.id == 'ATPM'
assert reaction.lower_bound == -100
assert reaction.upper_bound == 50
def test_add_metabolite(self, model):
with pytest.raises(ValueError):
model.add_metabolites(Metabolite())
with model:
with model:
reaction = model.reactions.get_by_id("PGI")
reaction.add_metabolites({model.metabolites[0]: 1})
assert model.metabolites[0] in reaction._metabolites
fake_metabolite = Metabolite("fake")
reaction.add_metabolites({fake_metabolite: 1})
assert fake_metabolite in reaction._metabolites
assert model.metabolites.has_id("fake")
assert model.metabolites.get_by_id("fake") is fake_metabolite
assert len(model._contexts[0]._history) == 0
assert fake_metabolite._model is None
assert fake_metabolite not in reaction._metabolites
assert "fake" not in model.metabolites
# test adding by string
with model:
reaction.add_metabolites({"g6p_c": -1}) # already in reaction
assert reaction._metabolites[model.metabolites.get_by_id(
"g6p_c")] == -2
reaction.add_metabolites({"h_c": 1})
assert reaction._metabolites[model.metabolites.get_by_id(
"h_c")] == 1
with pytest.raises(KeyError):
reaction.add_metabolites({"missing": 1})
assert reaction._metabolites[model.metabolites.get_by_id(
"g6p_c")] == -1
assert model.metabolites.h_c not in reaction._metabolites
# Test combine=False
reaction = model.reactions.get_by_id("ATPM")
old_stoich = reaction._metabolites[model.metabolites.get_by_id(
"h2o_c")]
with model:
reaction.add_metabolites({'h2o_c': 2.5}, combine=False)
assert reaction._metabolites[model.metabolites.get_by_id(
"h2o_c")] == 2.5
assert reaction._metabolites[model.metabolites.get_by_id(
"h2o_c")] == old_stoich
# test adding to a new Reaction
reaction = Reaction("test")
assert len(reaction._metabolites) == 0
reaction.add_metabolites({Metabolite("test_met"): -1})
assert len(reaction._metabolites) == 1
def construct_difference_model(model_1, model_2, norm_type='euclidean'):
"""Combine two models into a larger model that is designed to calculate differences
between the models
"""
#Get index mappings
common_dict = {}
#Using copies of the models so things are modified above
combined_model = model_1 = model_1.copy()
model_2 = model_2.copy()
for reaction_1 in model_1.reactions:
try:
reaction_2 = model_2.reactions.get_by_id(reaction_1.id)
common_dict[reaction_1] = reaction_2
except:
continue
#Add a prefix in front of the mutant_model metabolites and reactions to prevent
#name collisions in DictList
for the_dict_list in [model_2.metabolites,
model_2.reactions]:
[setattr(x, 'id', 'mutant_%s'%x.id)
for x in the_dict_list]
the_dict_list._generate_index() #Update the DictList.dicts
combined_model.add_reactions(model_2.reactions)
[setattr(x, 'objective_coefficient', 0.)
for x in combined_model.reactions]
#Add in the difference reactions. The mutant reactions and metabolites are already added.
#This must be a list to maintain the correct order when adding the difference_metabolites
difference_reactions = [] #Add the difference reactions at the end to speed things up
difference_metabolites = []
for reaction_1, reaction_2 in iteritems(common_dict):
reaction_1._difference_partner = reaction_2
reaction_2._difference_partner = reaction_1
difference_reaction = Reaction('difference_%s'%reaction_1.id)
difference_reactions.append(difference_reaction)
difference_reaction.upper_bound = 100000
difference_reaction.lower_bound = -1* difference_reaction.upper_bound
difference_metabolite = Metabolite('difference_%s'%reaction_1.id)
difference_metabolites.append(difference_metabolite)
if norm_type == 'linear':
difference_metabolite._constraint_sense = 'G'
reaction_1.add_metabolites({difference_metabolite: -1.}, add_to_container_model=False)
reaction_2.add_metabolites({difference_metabolite: 1.}, add_to_container_model=False)
difference_reaction.add_metabolites({difference_metabolite: 1.}, add_to_container_model=False)
combined_model.add_metabolites(difference_metabolites)
combined_model.add_reactions(difference_reactions)
return(combined_model)
def test_inequality(self, solver_test):
solver, old_solution, infeasible_model = solver_test
# The space enclosed by the constraints is a 2D triangle with
# vertexes as (3, 0), (1, 2), and (0, 1)
# 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"
assert abs(solver.solve(m).f - 1.0) < 10 ** -3
assert abs(solver.solve(m).x_dict["y"] - 2.0) < 10 ** -3
m.objective = "y"
assert abs(solver.solve(m).f - 3.0) < 10 ** -3
assert abs(
solver.solve(m, objective_sense="minimize").f - 1.0) < 10 ** -3
def geometric_fba_model():
"""
Generate geometric FBA model as described in [1]_
References
----------
.. [1] Smallbone, Kieran & Simeonidis, Vangelis. (2009).
Flux balance analysis: A geometric perspective.
Journal of theoretical biology.258. 311-5.
10.1016/j.jtbi.2009.01.027.
"""
test_model = Model("geometric_fba_paper_model")
test_model.add_metabolites(Metabolite("A"))
test_model.add_metabolites(Metabolite("B"))
v_1 = Reaction("v1", upper_bound=1.0)
v_1.add_metabolites({test_model.metabolites.A: 1.0})
v_2 = Reaction("v2", lower_bound=-1000.0)
v_2.add_metabolites({
test_model.metabolites.A: -1.0,
test_model.metabolites.B: 1.0
})
v_3 = Reaction("v3", lower_bound=-1000.0)
v_3.add_metabolites({
test_model.metabolites.A: -1.0,
test_model.metabolites.B: 1.0
})
v_4 = Reaction("v4", lower_bound=-1000.0)
v_4.add_metabolites({
test_model.metabolites.A: -1.0,
test_model.metabolites.B: 1.0
})
v_5 = Reaction("v5")
v_5.add_metabolites({
test_model.metabolites.A: 0.0,
test_model.metabolites.B: -1.0
})
test_model.add_reactions([v_1, v_2, v_3, v_4, v_5])
test_model.objective = "v5"
return test_model
def test_add_reactions_duplicate(model):
rxn = model.reactions[0]
r1 = Reaction("r1")
r1.add_metabolites({Metabolite("A"): -1, Metabolite("B"): 1})
r1.lower_bound, r1.upper_bound = -999999.0, 999999.0
r2 = Reaction(rxn.id)
r2.add_metabolites({
Metabolite("A"): -1,
Metabolite("C"): 1,
Metabolite("D"): 1
})
model.add_reactions([r1, r2])
assert r1 in model.reactions
assert rxn in model.reactions
assert r2 is not model.reactions.get_by_id(rxn.id)
def test_complicated_model():
"""Test a complicated model.
Difficult model since the online mean calculation is numerically
unstable so many samples weakly violate the equality constraints.
"""
model = Model('flux_split')
reaction1 = Reaction('V1')
reaction2 = Reaction('V2')
reaction3 = Reaction('V3')
reaction1.bounds = (0, 6)
reaction2.bounds = (0, 8)
reaction3.bounds = (0, 10)
A = Metabolite('A')
reaction1.add_metabolites({A: -1})
reaction2.add_metabolites({A: -1})
reaction3.add_metabolites({A: 1})
model.add_reactions([reaction1, reaction2, reaction3])
optgp = OptGPSampler(model, 1, seed=42)
achr = ACHRSampler(model, seed=42)
optgp_samples = optgp.sample(100)
achr_samples = achr.sample(100)
assert any(optgp_samples.corr().abs() < 1.0)
assert any(achr_samples.corr().abs() < 1.0)
# > 95% are valid
assert sum(optgp.validate(optgp_samples) == "v") > 95
assert sum(achr.validate(achr_samples) == "v") > 95
def test_model_remove_reaction(model):
old_reaction_count = len(model.reactions)
with model:
model.remove_reactions(["PGI"])
assert len(model.reactions) == old_reaction_count - 1
with pytest.raises(KeyError):
model.reactions.get_by_id("PGI")
model.remove_reactions(model.reactions[:1])
assert len(model.reactions) == old_reaction_count - 2
assert len(model.reactions) == old_reaction_count
assert "PGI" in model.reactions
tmp_metabolite = Metabolite("testing")
model.reactions[0].add_metabolites({tmp_metabolite: 1})
assert tmp_metabolite in model.metabolites
model.remove_reactions(model.reactions[:1], remove_orphans=True)
assert tmp_metabolite not in model.metabolites
with model:
model.reactions[0].add_metabolites({tmp_metabolite: 1})
assert tmp_metabolite in model.metabolites
assert tmp_metabolite not in model.metabolites
biomass_before = model.slim_optimize()
with model:
model.remove_reactions([model.reactions.Biomass_Ecoli_core])
assert np.isclose(model.slim_optimize(), 0)
assert np.isclose(model.slim_optimize(), biomass_before)
def test_reaction_delete(self, model):
old_reaction_count = len(model.reactions)
tmp_metabolite = Metabolite("testing")
# Delete without removing orphan
model.reactions[0].add_metabolites({tmp_metabolite: 1})
assert len(tmp_metabolite.reactions) == 1
model.reactions[0].delete(remove_orphans=False)
# make sure it's still in the model
assert tmp_metabolite in model.metabolites
assert len(tmp_metabolite.reactions) == 0
assert len(model.reactions) == old_reaction_count - 1
# Now try it with removing orphans
model.reactions[0].add_metabolites({tmp_metabolite: 1})
assert len(tmp_metabolite.reactions) == 1
model.reactions[0].delete(remove_orphans=True)
assert tmp_metabolite not in model.metabolites
assert len(tmp_metabolite.reactions) == 0
assert len(model.reactions) == old_reaction_count - 2
# It shouldn't remove orphans if it's in 2 reactions however
model.reactions[0].add_metabolites({tmp_metabolite: 1})
model.reactions[1].add_metabolites({tmp_metabolite: 1})
assert len(tmp_metabolite.reactions) == 2
model.reactions[0].delete(remove_orphans=False)
assert tmp_metabolite in model.metabolites
assert len(tmp_metabolite.reactions) == 1
assert len(model.reactions) == old_reaction_count - 3
def test_complicated_model(self):
"""Difficult model since the online mean calculation is numerically
unstable so many samples weakly violate the equality constraints."""
model = Model('flux_split')
reaction1 = Reaction('V1')
reaction2 = Reaction('V2')
reaction3 = Reaction('V3')
reaction1.lower_bound = 0
reaction2.lower_bound = 0
reaction3.lower_bound = 0
reaction1.upper_bound = 6
reaction2.upper_bound = 8
reaction3.upper_bound = 10
A = Metabolite('A')
reaction1.add_metabolites({A: -1})
reaction2.add_metabolites({A: -1})
reaction3.add_metabolites({A: 1})
model.add_reactions([reaction1])
model.add_reactions([reaction2])
model.add_reactions([reaction3])
optgp = OptGPSampler(model, 1, seed=42)
achr = ACHRSampler(model, seed=42)
optgp_samples = optgp.sample(100)
achr_samples = achr.sample(100)
assert any(optgp_samples.corr().abs() < 1.0)
assert any(achr_samples.corr().abs() < 1.0)
# > 95% are valid
assert (sum(optgp.validate(optgp_samples) == "v") > 95)
assert (sum(achr.validate(achr_samples) == "v") > 95)
def convert_to_irreversible_with_indicators(cobra_model,reaction_id_list,metabolite_list, mutually_exclusive_directionality_constraint = False,label_model=None):
#Function modified from the work by : """Schmidt BJ1, Ebrahim A, Metz TO, Adkins JN, Palsson B, Hyduke DR. GIM3E: condition-specific models of cellular metabolism developed from metabolomics and expression data Bioinformatics. 2013 Nov 15;29(22):2900-8. doi: 10.1093/bioinformatics/btt493. Epub 2013 Aug 23."""
"""Will break all of the reversible reactions into two separate irreversible
reactions with different directions. This function call modified from
a version in the core cobra to facilitate the MILP formulation and
include gene_reaction_rules with the reverse reaction
Arguments:
cobra_model: A model object which will be modified in place.
mutually_exclusive_directionality_constraint: Boolean. If True, turnover
reactions are constructed to serve as MILP constraints to prevent loops.
Returns:
None, cobra_model is modified in place
"""
reactions_to_add = []
from cobra.core.Reaction import Reaction
from cobra.core import Metabolite
reactions_to_make_irreversible=[]
for x in reaction_id_list:
reactions_to_make_irreversible.append(cobra_model.reactions.get_by_id(x))
"""for x in lexs:
reactions_to_make_irreversible.append(cobra_model.reactions.get_by_id(x))"""
#If a label model object is provided make sure all experimentally measured metabolites (or at least one of the metabolites in the pool) is produced
full_metabolite_list=copy.copy(metabolite_list)
print full_metabolite_list
if label_model!=None:
emus=[]
for condition in label_model.experimental_dict:
for emu in label_model.experimental_dict[condition]:
if emu not in emus:
emus.append(emu)
measured_metabolite_dict={}
for emu in emus:
iso_id=str(label_model.emu_dict[emu]["met_id"])
#print label_model.id_isotopomer_object_dict
#isotopomer_object=label_model.id_isotopomer_object_dict[iso_id]
metabolites=label_model.isotopomer_id_metabolite_id_dict[iso_id]
print [iso_id,label_model.isotopomer_id_metabolite_id_dict[iso_id]]
if isinstance(metabolites,list):
for metabolite in metabolites:
full_metabolite_list.append(metabolite)
else:
full_metabolite_list.append(metabolites)
for metabolites in full_metabolite_list:
print metabolites
if not isinstance(metabolites,list):
metabolites=[metabolites]
for metabolite in metabolites:
print metabolite
the_metabolite=cobra_model.metabolites.get_by_id(metabolite)
for x in the_metabolite.reactions:
if x not in reactions_to_make_irreversible:
reactions_to_make_irreversible.append(x)
for reaction in reactions_to_make_irreversible:
# Potential artifact because a reaction might run backwards naturally
# and this would result in adding an empty reaction to the
# model in addition to the reverse reaction.
if reaction.lower_bound < 0:
#reverse_reaction = Reaction(reaction.id + "_reverse")
reverse_reaction = reaction.copy()
reverse_reaction.id = reaction.id + "_reverse"
reverse_reaction.lower_bound = max(0,-1*reaction.upper_bound)
reverse_reaction.upper_bound = reaction.lower_bound * -1.
reaction.lower_bound = 0
if reaction.upper_bound<0:
reaction.upper_bound=0
# Make the directions aware of each other
reaction.notes["reflection"] = reverse_reaction.id
reverse_reaction.notes["reflection"] = reaction.id
reaction_dict = {}
current_metabolites = [x for x in reaction.metabolites]
for the_metabolite in current_metabolites:
reaction_dict[the_metabolite] = -2 * reaction.get_coefficient(the_metabolite.id)
reverse_reaction.add_metabolites(reaction_dict)
reactions_to_add.append(reverse_reaction)
# Also: GPRs should already copy
# reverse_reaction.gene_reaction_rule = reaction.gene_reaction_rule
# reverse_reaction._genes = reaction._genes
if mutually_exclusive_directionality_constraint:
# A continuous reaction bounded by 0., 1.
# Serves as a source for the indicator metabolites
tmp_source = Reaction('IRRMILP_direction_constraint_source_for_%s_and_%s'
%(reaction.id,
reverse_reaction.id))
tmp_source.upper_bound = 1.
tmp_source.lower_bound = 0.
# The reverse indicator reaction is
# an integer-valued reaction bounded by 0,1
# that activates flux to the reverse reaction
# and deactivates the forward reaction only when it is
# turned on to 1
tmp_indicator = Reaction('IRRMILP_reverse_indicator_for_%s_and_%s'
%(reaction.id,
reverse_reaction.id))
tmp_indicator.upper_bound = 1
tmp_indicator.lower_bound = 0
tmp_indicator.variable_kind = 'integer'
flux_constraint_forward = Metabolite(id =
'IRRMILP_direction_constraint_for_%s'%reaction.id)
flux_constraint_reverse = Metabolite(id =
'IRRMILP_direction_constraint_for_%s'%reverse_reaction.id)
flux_constraint_reverse._constraint_sense = 'G'
flux_constraint_reverse._bound = 0.
tmp_source.add_metabolites({flux_constraint_forward: 1})
tmp_indicator.add_metabolites({flux_constraint_forward: -1,
flux_constraint_reverse: 1})
if reaction.upper_bound != 0:
reaction.add_metabolites({flux_constraint_forward: -1./reaction.upper_bound})
else:
# could put 1.01 X the tolerance here,
# This is arbitrary. Use 0.001
# since 1000 is a typical upper bound
reaction.add_metabolites({flux_constraint_forward: -0.001})
if reverse_reaction.upper_bound != 0:
reverse_reaction.add_metabolites({flux_constraint_reverse: -1./reverse_reaction.upper_bound})
else:
reverse_reaction.add_metabolites({flux_constraint_reverse: -0.001})
reactions_to_add.append(tmp_indicator)
reactions_to_add.append(tmp_source)
cobra_model.add_reactions(reactions_to_add)
def test_metabolite_formula():
met = Metabolite("water")
met.formula = "H2O"
assert met.elements == {"H": 2, "O": 1}
assert met.formula_weight == 18.01528
def from_mat_struct(mat_struct, model_id=None, inf=inf):
"""create a model from the COBRA toolbox struct
The struct will be a dict read in by scipy.io.loadmat
"""
m = mat_struct
if m.dtype.names is None:
raise ValueError("not a valid mat struct")
if not {"rxns", "mets", "S", "lb", "ub"} <= set(m.dtype.names):
raise ValueError("not a valid mat struct")
if "c" in m.dtype.names:
c_vec = m["c"][0, 0]
else:
c_vec = None
warn("objective vector 'c' not found")
model = Model()
if model_id is not None:
model.id = model_id
elif "description" in m.dtype.names:
description = m["description"][0, 0][0]
if not isinstance(description, string_types) and len(description) > 1:
model.id = description[0]
warn("Several IDs detected, only using the first.")
else:
model.id = description
else:
model.id = "imported_model"
for i, name in enumerate(m["mets"][0, 0]):
new_metabolite = Metabolite()
new_metabolite.id = str(name[0][0])
if all(var in m.dtype.names for var in
['metComps', 'comps', 'compNames']):
comp_index = m["metComps"][0, 0][i][0] - 1
new_metabolite.compartment = m['comps'][0, 0][comp_index][0][0]
if new_metabolite.compartment not in model.compartments:
comp_name = m['compNames'][0, 0][comp_index][0][0]
model.compartments[new_metabolite.compartment] = comp_name
else:
new_metabolite.compartment = _get_id_compartment(new_metabolite.id)
if new_metabolite.compartment not in model.compartments:
model.compartments[
new_metabolite.compartment] = new_metabolite.compartment
try:
new_metabolite.name = str(m["metNames"][0, 0][i][0][0])
except (IndexError, ValueError):
pass
try:
new_metabolite.formula = str(m["metFormulas"][0][0][i][0][0])
except (IndexError, ValueError):
pass
try:
new_metabolite.charge = float(m["metCharge"][0, 0][i][0])
int_charge = int(new_metabolite.charge)
if new_metabolite.charge == int_charge:
new_metabolite.charge = int_charge
except (IndexError, ValueError):
pass
model.add_metabolites([new_metabolite])
new_reactions = []
coefficients = {}
for i, name in enumerate(m["rxns"][0, 0]):
new_reaction = Reaction()
new_reaction.id = str(name[0][0])
new_reaction.lower_bound = float(m["lb"][0, 0][i][0])
new_reaction.upper_bound = float(m["ub"][0, 0][i][0])
if isinf(new_reaction.lower_bound) and new_reaction.lower_bound < 0:
new_reaction.lower_bound = -inf
if isinf(new_reaction.upper_bound) and new_reaction.upper_bound > 0:
new_reaction.upper_bound = inf
if c_vec is not None:
coefficients[new_reaction] = float(c_vec[i][0])
try:
new_reaction.gene_reaction_rule = str(m['grRules'][0, 0][i][0][0])
except (IndexError, ValueError):
pass
try:
new_reaction.name = str(m["rxnNames"][0, 0][i][0][0])
except (IndexError, ValueError):
pass
try:
new_reaction.subsystem = str(m['subSystems'][0, 0][i][0][0])
except (IndexError, ValueError):
pass
new_reactions.append(new_reaction)
model.add_reactions(new_reactions)
set_objective(model, coefficients)
coo = scipy_sparse.coo_matrix(m["S"][0, 0])
for i, j, v in zip(coo.row, coo.col, coo.data):
model.reactions[j].add_metabolites({model.metabolites[i]: v})
return model
def create_cobra_model_from_sbml_file(sbml_filename, old_sbml=False,
legacy_metabolite=False,
print_time=False, use_hyphens=False):
"""convert an SBML XML file into a cobra.Model object.
Supports SBML Level 2 Versions 1 and 4. The function will detect if the
SBML fbc package is used in the file and run the converter if the fbc
package is used.
Parameters
----------
sbml_filename: string
old_sbml: bool
Set to True if the XML file has metabolite formula appended to
metabolite names. This was a poorly designed artifact that persists in
some models.
legacy_metabolite: bool
If True then assume that the metabolite id has the compartment id
appended after an underscore (e.g. _c for cytosol). This has not been
implemented but will be soon.
print_time: bool
deprecated
use_hyphens: bool
If True, double underscores (__) in an SBML ID will be converted to
hyphens
Returns
-------
Model : The parsed cobra model
"""
if not libsbml:
raise ImportError('create_cobra_model_from_sbml_file '
'requires python-libsbml')
__default_lower_bound = -1000
__default_upper_bound = 1000
__default_objective_coefficient = 0
# Ensure that the file exists
if not isfile(sbml_filename):
raise IOError('Your SBML file is not found: %s' % sbml_filename)
# Expressions to change SBML Ids to Palsson Lab Ids
metabolite_re = re.compile('^M_')
reaction_re = re.compile('^R_')
compartment_re = re.compile('^C_')
if print_time:
warn("print_time is deprecated", DeprecationWarning)
model_doc = libsbml.readSBML(sbml_filename)
if model_doc.getPlugin("fbc") is not None:
from libsbml import ConversionProperties, LIBSBML_OPERATION_SUCCESS
conversion_properties = ConversionProperties()
conversion_properties.addOption(
"convert fbc to cobra", True, "Convert FBC model to Cobra model")
result = model_doc.convert(conversion_properties)
if result != LIBSBML_OPERATION_SUCCESS:
raise Exception("Conversion of SBML+fbc to COBRA failed")
sbml_model = model_doc.getModel()
sbml_model_id = sbml_model.getId()
sbml_species = sbml_model.getListOfSpecies()
sbml_reactions = sbml_model.getListOfReactions()
sbml_compartments = sbml_model.getListOfCompartments()
compartment_dict = dict([(compartment_re.split(x.getId())[-1], x.getName())
for x in sbml_compartments])
if legacy_metabolite:
# Deal with the palsson lab appending the compartment id to the
# metabolite id
new_dict = {}
for the_id, the_name in compartment_dict.items():
if the_name == '':
new_dict[the_id[0].lower()] = the_id
else:
new_dict[the_id] = the_name
compartment_dict = new_dict
legacy_compartment_converter = dict(
[(v, k) for k, v in iteritems(compartment_dict)])
cobra_model = Model(sbml_model_id)
metabolites = []
metabolite_dict = {}
# Convert sbml_metabolites to cobra.Metabolites
for sbml_metabolite in sbml_species:
# Skip sbml boundary species
if sbml_metabolite.getBoundaryCondition():
continue
if (old_sbml or legacy_metabolite) and \
sbml_metabolite.getId().endswith('_b'):
# Deal with incorrect sbml from bigg.ucsd.edu
continue
tmp_metabolite = Metabolite()
metabolite_id = tmp_metabolite.id = sbml_metabolite.getId()
tmp_metabolite.compartment = compartment_re.split(
sbml_metabolite.getCompartment())[-1]
if legacy_metabolite:
if tmp_metabolite.compartment not in compartment_dict:
tmp_metabolite.compartment = legacy_compartment_converter[
tmp_metabolite.compartment]
tmp_metabolite.id = parse_legacy_id(
tmp_metabolite.id, tmp_metabolite.compartment,
use_hyphens=use_hyphens)
if use_hyphens:
tmp_metabolite.id = metabolite_re.split(
tmp_metabolite.id)[-1].replace('__', '-')
else:
# Just in case the SBML ids are ill-formed and use -
tmp_metabolite.id = metabolite_re.split(
tmp_metabolite.id)[-1].replace('-', '__')
tmp_metabolite.name = sbml_metabolite.getName()
tmp_formula = ''
tmp_metabolite.notes = parse_legacy_sbml_notes(
sbml_metabolite.getNotesString())
if sbml_metabolite.isSetCharge():
tmp_metabolite.charge = sbml_metabolite.getCharge()
if "CHARGE" in tmp_metabolite.notes:
note_charge = tmp_metabolite.notes["CHARGE"][0]
try:
note_charge = float(note_charge)
if note_charge == int(note_charge):
note_charge = int(note_charge)
except:
warn("charge of %s is not a number (%s)" %
(tmp_metabolite.id, str(note_charge)))
else:
if ((tmp_metabolite.charge is None) or
(tmp_metabolite.charge == note_charge)):
tmp_metabolite.notes.pop("CHARGE")
# set charge to the one from notes if not assigend before
# the same
tmp_metabolite.charge = note_charge
else: # tmp_metabolite.charge != note_charge
msg = "different charges specified for %s (%d and %d)"
msg = msg % (tmp_metabolite.id,
tmp_metabolite.charge, note_charge)
warn(msg)
# Chances are a 0 note charge was written by mistake. We
# will default to the note_charge in this case.
if tmp_metabolite.charge == 0:
tmp_metabolite.charge = note_charge
for the_key in tmp_metabolite.notes.keys():
if the_key.lower() == 'formula':
tmp_formula = tmp_metabolite.notes.pop(the_key)[0]
break
if tmp_formula == '' and old_sbml:
tmp_formula = tmp_metabolite.name.split('_')[-1]
tmp_metabolite.name = tmp_metabolite.name[:-len(tmp_formula) - 1]
tmp_metabolite.formula = tmp_formula
metabolite_dict.update({metabolite_id: tmp_metabolite})
metabolites.append(tmp_metabolite)
cobra_model.add_metabolites(metabolites)
# Construct the vectors and matrices for holding connectivity and numerical
# info to feed to the cobra toolbox.
# Always assume steady state simulations so b is set to 0
cobra_reaction_list = []
coefficients = {}
for sbml_reaction in sbml_reactions:
if use_hyphens:
# Change the ids to match conventions used by the Palsson lab.
reaction = Reaction(reaction_re.split(
sbml_reaction.getId())[-1].replace('__', '-'))
else:
# Just in case the SBML ids are ill-formed and use -
reaction = Reaction(reaction_re.split(
sbml_reaction.getId())[-1].replace('-', '__'))
cobra_reaction_list.append(reaction)
# reaction.exchange_reaction = 0
reaction.name = sbml_reaction.getName()
cobra_metabolites = {}
# Use the cobra.Metabolite class here
for sbml_metabolite in sbml_reaction.getListOfReactants():
tmp_metabolite_id = sbml_metabolite.getSpecies()
# This deals with boundary metabolites
if tmp_metabolite_id in metabolite_dict:
tmp_metabolite = metabolite_dict[tmp_metabolite_id]
cobra_metabolites[tmp_metabolite] = - \
sbml_metabolite.getStoichiometry()
for sbml_metabolite in sbml_reaction.getListOfProducts():
tmp_metabolite_id = sbml_metabolite.getSpecies()
# This deals with boundary metabolites
if tmp_metabolite_id in metabolite_dict:
tmp_metabolite = metabolite_dict[tmp_metabolite_id]
# Handle the case where the metabolite was specified both
# as a reactant and as a product.
if tmp_metabolite in cobra_metabolites:
warn("%s appears as a reactant and product %s" %
(tmp_metabolite_id, reaction.id))
cobra_metabolites[
tmp_metabolite] += sbml_metabolite.getStoichiometry()
# if the combined stoichiometry is 0, remove the metabolite
if cobra_metabolites[tmp_metabolite] == 0:
cobra_metabolites.pop(tmp_metabolite)
else:
cobra_metabolites[
tmp_metabolite] = sbml_metabolite.getStoichiometry()
# check for nan
for met, v in iteritems(cobra_metabolites):
if isnan(v) or isinf(v):
warn("invalid value %s for metabolite '%s' in reaction '%s'" %
(str(v), met.id, reaction.id))
reaction.add_metabolites(cobra_metabolites)
# Parse the kinetic law info here.
parameter_dict = {}
# If lower and upper bounds are specified in the Kinetic Law then
# they override the sbml reversible attribute. If they are not
# specified then the bounds are determined by getReversible.
if not sbml_reaction.getKineticLaw():
if sbml_reaction.getReversible():
parameter_dict['lower_bound'] = __default_lower_bound
parameter_dict['upper_bound'] = __default_upper_bound
else:
# Assume that irreversible reactions only proceed from left to
# right.
parameter_dict['lower_bound'] = 0
parameter_dict['upper_bound'] = __default_upper_bound
parameter_dict[
'objective_coefficient'] = __default_objective_coefficient
else:
for sbml_parameter in \
sbml_reaction.getKineticLaw().getListOfParameters():
parameter_dict[
sbml_parameter.getId().lower()] = sbml_parameter.getValue()
if 'lower_bound' in parameter_dict:
reaction.lower_bound = parameter_dict['lower_bound']
elif 'lower bound' in parameter_dict:
reaction.lower_bound = parameter_dict['lower bound']
elif sbml_reaction.getReversible():
reaction.lower_bound = __default_lower_bound
else:
reaction.lower_bound = 0
if 'upper_bound' in parameter_dict:
reaction.upper_bound = parameter_dict['upper_bound']
elif 'upper bound' in parameter_dict:
reaction.upper_bound = parameter_dict['upper bound']
else:
reaction.upper_bound = __default_upper_bound
objective_coefficient = parameter_dict.get(
'objective_coefficient', parameter_dict.get(
'objective_coefficient', __default_objective_coefficient))
if objective_coefficient != 0:
coefficients[reaction] = objective_coefficient
# ensure values are not set to nan or inf
if isnan(reaction.lower_bound) or isinf(reaction.lower_bound):
reaction.lower_bound = __default_lower_bound
if isnan(reaction.upper_bound) or isinf(reaction.upper_bound):
reaction.upper_bound = __default_upper_bound
reaction_note_dict = parse_legacy_sbml_notes(
sbml_reaction.getNotesString())
# Parse the reaction notes.
# POTENTIAL BUG: DEALING WITH LEGACY 'SBML' THAT IS NOT IN A
# STANDARD FORMAT
# TODO: READ IN OTHER NOTES AND GIVE THEM A reaction_ prefix.
# TODO: Make sure genes get added as objects
if 'GENE ASSOCIATION' in reaction_note_dict:
rule = reaction_note_dict['GENE ASSOCIATION'][0]
try:
rule.encode('ascii')
except (UnicodeEncodeError, UnicodeDecodeError):
warn("gene_reaction_rule '%s' is not ascii compliant" % rule)
if rule.startswith(""") and rule.endswith("""):
rule = rule[6:-6]
reaction.gene_reaction_rule = rule
if 'GENE LIST' in reaction_note_dict:
reaction.systematic_names = reaction_note_dict['GENE LIST'][0]
elif ('GENES' in reaction_note_dict and
reaction_note_dict['GENES'] != ['']):
reaction.systematic_names = reaction_note_dict['GENES'][0]
elif 'LOCUS' in reaction_note_dict:
gene_id_to_object = dict([(x.id, x) for x in reaction._genes])
for the_row in reaction_note_dict['LOCUS']:
tmp_row_dict = {}
the_row = 'LOCUS:' + the_row.lstrip('_').rstrip('#')
for the_item in the_row.split('#'):
k, v = the_item.split(':')
tmp_row_dict[k] = v
tmp_locus_id = tmp_row_dict['LOCUS']
if 'TRANSCRIPT' in tmp_row_dict:
tmp_locus_id = tmp_locus_id + \
'.' + tmp_row_dict['TRANSCRIPT']
if 'ABBREVIATION' in tmp_row_dict:
gene_id_to_object[tmp_locus_id].name = tmp_row_dict[
'ABBREVIATION']
if 'SUBSYSTEM' in reaction_note_dict:
reaction.subsystem = reaction_note_dict.pop('SUBSYSTEM')[0]
reaction.notes = reaction_note_dict
# Now, add all of the reactions to the model.
cobra_model.id = sbml_model.getId()
# Populate the compartment list - This will be done based on
# cobra.Metabolites in cobra.Reactions in the future.
cobra_model.compartments = compartment_dict
cobra_model.add_reactions(cobra_reaction_list)
set_objective(cobra_model, coefficients)
return cobra_model
def moma(wt_model, mutant_model, objective_sense='maximize', solver=None,
tolerance_optimality=1e-8, tolerance_feasibility=1e-8,
minimize_norm=True, norm_flux_dict=None, the_problem='return', lp_method=0,
combined_model=None, norm_type='euclidean'):
"""Runs the minimization of metabolic adjustment method described in
Segre et al 2002 PNAS 99(23): 15112-7.
wt_model: A cobra.Model object
mutant_model: A cobra.Model object with different reaction bounds vs wt_model.
objective_sense: 'maximize' or 'minimize'
solver: 'gurobi', 'cplex', or 'glpk'. Note: glpk cannot be used with norm_type 'euclidean'
tolerance_optimality: Solver tolerance for optimality.
tolerance_feasibility: Solver tolerance for feasibility.
the_problem: None or a problem object for the specific solver that can be
used to hot start the next solution.
lp_method: The method to use for solving the problem. Depends on the solver. See
the cobra.flux_analysis.solvers.py file for more info.
For norm_type == 'euclidean':
the primal simplex works best for the test model (gurobi: lp_method=0, cplex: lp_method=1)
combined_model: an output from moma that represents the combined optimization to be solved.
"""
if solver is None:
if norm_type == "euclidean":
solver = get_solver_name(qp=True)
else:
solver = get_solver_name() # linear is not even implemented yet
if combined_model is not None or the_problem not in ['return']:
warn("moma currently does not support reusing models or problems. " +\
"continuing without them")
combined_model = None
the_problem = 'return'
if solver.lower() == 'cplex' and lp_method == 0:
#print 'for moma, solver method 0 is very slow for cplex. changing to method 1'
lp_method = 1
if solver.lower() == 'glpk' and norm_type == 'euclidean':
try:
# from gurobipy import Model
solver = 'gurobi'
warn("GLPK can't solve quadratic problems like MOMA. Switched solver to %s"%solver)
except:
warn("GLPK can't solve quadratic problems like MOMA. Switching to linear MOMA")
if norm_type == 'euclidean':
#Reusing the basis can get the solver stuck.
reuse_basis = False
if combined_model and combined_model.norm_type != norm_type:
print('Cannot use combined_model.norm_type = %s with user-specified norm type'%(combined_model.norm_type,
norm_type))
print('Defaulting to user-specified norm_type')
combined_model = None
if norm_type == 'linear':
raise Exception('linear MOMA is not currently implmented')
quadratic_component = None
if minimize_norm:
if norm_flux_dict is None:
optimize_minimum_flux(wt_model, objective_sense='maximize',
tolerance_feasibility=tolerance_feasibility)
norm_flux_dict = wt_model.solution.x_dict
else:
# update the solution of wt model according to norm_flux_dict
wt_model.optimize() # this is just to make sure wt_model.solution and mutant_model.solution refer to different object.
objective_reaction_coefficient_dict = dict([(x.id, x.objective_coefficient)
for x in wt_model.reactions
if x.objective_coefficient])
try:
wt_model.solution.f = sum([norm_flux_dict[k] * v for k, v in
objective_reaction_coefficient_dict.items()])
wt_model.solution.x_dict = norm_flux_dict
except:
print('incorrect norm_flux_dict')
raise
# formulate qMOMA using wt_flux as reference
# make a copy not to change the objective coefficients of original mutant model
mutant_model_moma = mutant_model.copy()
nRxns = len(mutant_model_moma.reactions)
quadratic_component = 2 * eye(nRxns, nRxns)
# linear component
[setattr(x, 'objective_coefficient', -2 * norm_flux_dict[x.id]) for x in mutant_model_moma.reactions]
the_problem = mutant_model_moma.optimize(objective_sense='minimize',
quadratic_component=quadratic_component,
solver=solver,
tolerance_optimality=tolerance_optimality,
tolerance_feasibility=tolerance_feasibility,
lp_method=lp_method)
#, reuse_basis=reuse_basis) # this should be commented out when solver is 'cplex'
if mutant_model_moma.solution.status != 'optimal':
warn('optimal moma solution not found: solver status %s'%mutant_model_moma.solution.status +\
' returning the problem, the_combined model, and the quadratic component for trouble shooting')
return(the_problem, mutant_model_moma, quadratic_component)
solution = mutant_model_moma.solution
mutant_dict = {}
mutant_f = sum([mutant_model.reactions.get_by_id(x.id).objective_coefficient * x.x for x in mutant_model_moma.reactions])
mutant_dict['objective_value'] = mutant_f
mutant_dict['status'] = solution.status
#TODO: Deal with maximize / minimize issues for a reversible model that's been converted to irreversible
mutant_dict['flux_difference'] = flux_difference = sum([(norm_flux_dict[r.id] - mutant_model_moma.solution.x_dict[r.id])**2
for r in mutant_model_moma.reactions])
mutant_dict['the_problem'] = the_problem
mutant_dict['mutant_model'] = mutant_model_moma
# update the solution of original mutant model
mutant_model.solution.x_dict = the_problem.x_dict
mutant_model.solution.status = solution.status
mutant_model.solution.f = mutant_f
# del wt_model, mutant_model, quadratic_component, solution
return(mutant_dict)
else:
#Construct a problem that attempts to maximize the objective in the WT model while
#solving the quadratic problem. This new problem is constructed to try to find
#a solution for the WT model that lies close to the mutant model. There are
#often multiple equivalent solutions with M matrices and the one returned
#by a simple cobra_model.optimize call may be too far from the mutant.
#This only needs to be adjusted if we update mutant_model._S after deleting reactions
number_of_reactions_in_common = len(set([x.id for x in wt_model.reactions]).intersection([x.id for x in mutant_model.reactions]))
number_of_reactions = len(wt_model.reactions) + len(mutant_model.reactions)
#Get the optimal wt objective value and adjust based on optimality tolerances
wt_model.optimize(solver=solver)
wt_optimal = deepcopy(wt_model.solution.f)
if objective_sense == 'maximize':
wt_optimal = floor(wt_optimal/tolerance_optimality)*tolerance_optimality
else:
wt_optimal = ceil(wt_optimal/tolerance_optimality)*tolerance_optimality
if not combined_model:
#Collect the set of wt reactions contributing to the objective.
objective_reaction_coefficient_dict = dict([(x.id, x.objective_coefficient)
for x in wt_model.reactions
if x.objective_coefficient])
combined_model = construct_difference_model(wt_model, mutant_model, norm_type)
#Add in the virtual objective metabolite to constrain the wt_model to the space where
#the objective was maximal
objective_metabolite = Metabolite('wt_optimal')
objective_metabolite._bound = wt_optimal
if objective_sense == 'maximize':
objective_metabolite._constraint_sense = 'G'
else:
objective_metabolite._constraint_sense = 'L'
#TODO: this couples the wt_model objective reaction to the virtual metabolite
#Currently, assumes a single objective reaction; however, this may be extended
[combined_model.reactions.get_by_id(k).add_metabolites({objective_metabolite: v})
for k, v in objective_reaction_coefficient_dict.items()]
if norm_type == 'euclidean':
#Makes assumptions about the structure of combined model
quadratic_component = s_vstack((lil_matrix((number_of_reactions, number_of_reactions + number_of_reactions_in_common )),
s_hstack((lil_matrix((number_of_reactions_in_common, number_of_reactions)),
eye(number_of_reactions_in_common,number_of_reactions_in_common)))))
elif norm_type == 'linear':
quadratic_component = None
combined_model.norm_type = norm_type
cobra_model = combined_model
the_problem = combined_model.optimize(objective_sense='minimize',
quadratic_component=quadratic_component,
solver=solver,
tolerance_optimality=tolerance_optimality,
tolerance_feasibility=tolerance_feasibility,
lp_method=lp_method) #, reuse_basis=reuse_basis) # this should be commented out when solver is 'cplex'
if combined_model.solution.status != 'optimal':
warn('optimal moma solution not found: solver status %s'%combined_model.solution.status +\
' returning the problem, the_combined model, and the quadratic component for trouble shooting')
return(the_problem, combined_model, quadratic_component)
solution = combined_model.solution
mutant_dict = {}
#Might be faster to quey based on mutant_model.reactions with the 'mutant_' prefix added
_reaction_list = [x for x in combined_model.reactions if x.id.startswith('mutant_')]
mutant_f = sum([mutant_model.reactions.get_by_id(x.id[len('mutant_'):]).objective_coefficient *
x.x for x in _reaction_list])
mutant_dict['objective_value'] = mutant_f
wild_type_flux_total = sum([abs(solution.x_dict[x.id]) for x in wt_model.reactions])
mutant_flux_total = sum(abs(x.x) for x in _reaction_list)
#Need to use the new solution as there are multiple ways to achieve an optimal solution in
#simulations with M matrices.
mutant_dict['status'] = solution.status
#TODO: Deal with maximize / minimize issues for a reversible model that's been converted to irreversible
mutant_dict['flux_difference'] = flux_difference = sum([(solution.x_dict[x.id[len('mutant_'):]]
- x.x)**2 for x in _reaction_list])
mutant_dict['the_problem'] = the_problem
mutant_dict['combined_model'] = combined_model
del wt_model, mutant_model, quadratic_component, solution
return(mutant_dict)
def parse_xml_into_model(xml, number=float):
xml_model = xml.find(ns("sbml:model"))
if get_attrib(xml_model, "fbc:strict") != "true":
warn('loading SBML model without fbc:strict="true"')
model_id = get_attrib(xml_model, "id")
model = Model(model_id)
model.name = xml_model.get("name")
model.compartments = {c.get("id"): c.get("name") for c in
xml_model.findall(COMPARTMENT_XPATH)}
# add metabolites
for species in xml_model.findall(SPECIES_XPATH % 'false'):
met = get_attrib(species, "id", require=True)
met = Metabolite(clip(met, "M_"))
met.name = species.get("name")
annotate_cobra_from_sbml(met, species)
met.compartment = species.get("compartment")
met.charge = get_attrib(species, "fbc:charge", int)
met.formula = get_attrib(species, "fbc:chemicalFormula")
model.add_metabolites([met])
# Detect boundary metabolites - In case they have been mistakenly
# added. They should not actually appear in a model
boundary_metabolites = {clip(i.get("id"), "M_")
for i in xml_model.findall(SPECIES_XPATH % 'true')}
# add genes
for sbml_gene in xml_model.iterfind(GENES_XPATH):
gene_id = get_attrib(sbml_gene, "fbc:id").replace(SBML_DOT, ".")
gene = Gene(clip(gene_id, "G_"))
gene.name = get_attrib(sbml_gene, "fbc:name")
if gene.name is None:
gene.name = get_attrib(sbml_gene, "fbc:label")
annotate_cobra_from_sbml(gene, sbml_gene)
model.genes.append(gene)
def process_gpr(sub_xml):
"""recursively convert gpr xml to a gpr string"""
if sub_xml.tag == OR_TAG:
return "( " + ' or '.join(process_gpr(i) for i in sub_xml) + " )"
elif sub_xml.tag == AND_TAG:
return "( " + ' and '.join(process_gpr(i) for i in sub_xml) + " )"
elif sub_xml.tag == GENEREF_TAG:
gene_id = get_attrib(sub_xml, "fbc:geneProduct", require=True)
return clip(gene_id, "G_")
else:
raise Exception("unsupported tag " + sub_xml.tag)
bounds = {bound.get("id"): get_attrib(bound, "value", type=number)
for bound in xml_model.iterfind(BOUND_XPATH)}
# add reactions
reactions = []
for sbml_reaction in xml_model.iterfind(
ns("sbml:listOfReactions/sbml:reaction")):
reaction = get_attrib(sbml_reaction, "id", require=True)
reaction = Reaction(clip(reaction, "R_"))
reaction.name = sbml_reaction.get("name")
annotate_cobra_from_sbml(reaction, sbml_reaction)
lb_id = get_attrib(sbml_reaction, "fbc:lowerFluxBound", require=True)
ub_id = get_attrib(sbml_reaction, "fbc:upperFluxBound", require=True)
try:
reaction.upper_bound = bounds[ub_id]
reaction.lower_bound = bounds[lb_id]
except KeyError as e:
raise CobraSBMLError("No constant bound with id '%s'" % str(e))
reactions.append(reaction)
stoichiometry = defaultdict(lambda: 0)
for species_reference in sbml_reaction.findall(
ns("sbml:listOfReactants/sbml:speciesReference")):
met_name = clip(species_reference.get("species"), "M_")
stoichiometry[met_name] -= \
number(species_reference.get("stoichiometry"))
for species_reference in sbml_reaction.findall(
ns("sbml:listOfProducts/sbml:speciesReference")):
met_name = clip(species_reference.get("species"), "M_")
stoichiometry[met_name] += \
get_attrib(species_reference, "stoichiometry",
type=number, require=True)
# needs to have keys of metabolite objects, not ids
object_stoichiometry = {}
for met_id in stoichiometry:
if met_id in boundary_metabolites:
warn("Boundary metabolite '%s' used in reaction '%s'" %
(met_id, reaction.id))
continue
try:
metabolite = model.metabolites.get_by_id(met_id)
except KeyError:
warn("ignoring unknown metabolite '%s' in reaction %s" %
(met_id, reaction.id))
continue
object_stoichiometry[metabolite] = stoichiometry[met_id]
reaction.add_metabolites(object_stoichiometry)
# set gene reaction rule
gpr_xml = sbml_reaction.find(GPR_TAG)
if gpr_xml is not None and len(gpr_xml) != 1:
warn("ignoring invalid geneAssociation for " + repr(reaction))
gpr_xml = None
gpr = process_gpr(gpr_xml[0]) if gpr_xml is not None else ''
# remove outside parenthesis, if any
if gpr.startswith("(") and gpr.endswith(")"):
gpr = gpr[1:-1].strip()
gpr = gpr.replace(SBML_DOT, ".")
reaction.gene_reaction_rule = gpr
try:
model.add_reactions(reactions)
except ValueError as e:
warn(str(e))
# objective coefficients are handled after all reactions are added
obj_list = xml_model.find(ns("fbc:listOfObjectives"))
if obj_list is None:
warn("listOfObjectives element not found")
return model
target_objective_id = get_attrib(obj_list, "fbc:activeObjective")
target_objective = obj_list.find(
ns("fbc:objective[@fbc:id='{}']".format(target_objective_id)))
obj_direction_long = get_attrib(target_objective, "fbc:type")
obj_direction = LONG_SHORT_DIRECTION[obj_direction_long]
obj_query = OBJECTIVES_XPATH % target_objective_id
coefficients = {}
for sbml_objective in obj_list.findall(obj_query):
rxn_id = clip(get_attrib(sbml_objective, "fbc:reaction"), "R_")
try:
objective_reaction = model.reactions.get_by_id(rxn_id)
except KeyError:
raise CobraSBMLError("Objective reaction '%s' not found" % rxn_id)
try:
coefficients[objective_reaction] = get_attrib(
sbml_objective, "fbc:coefficient", type=number)
except ValueError as e:
warn(str(e))
set_objective(model, coefficients)
model.solver.objective.direction = obj_direction
return model
def optimize_minimum_flux(model, objective_sense='maximize',
tolerance_optimality=1e-8, tolerance_feasibility=1e-8):
# return the flux distribution in which the total amount of fluxes is minimum while the growth is maximum
#Get the optimal wt objective value and adjust based on optimality tolerances
model.optimize()
optimal_value = deepcopy(model.solution.f)
# print('opt val: %s' % optimal_value)
if objective_sense == 'maximize':
optimal_value = floor(optimal_value/tolerance_optimality)*tolerance_optimality
else:
optimal_value = ceil(optimal_value/tolerance_optimality)*tolerance_optimality
# print('adjusted opt val: %s' % optimal_value)
#Add in the virtual objective metabolite to constrain the wt_model to the space where
#the objective was maximal
objective_metabolite = Metabolite('objective metabolite')
objective_metabolite._bound = optimal_value
if objective_sense == 'maximize':
objective_metabolite._constraint_sense = 'G'
else:
objective_metabolite._constraint_sense = 'L'
# print('objm const sense: %s, objm bound: %s' % (objective_metabolite._constraint_sense, objective_metabolite._bound))
# construct irreversible model to assure all flux values are positive
irreve_model = model.copy()
# this is necessary to avoid invalid bound error when model is changed to irreversible
for r in irreve_model.reactions:
if r.upper_bound < 0:
reverse_reaction = Reaction(r.id + "_reverse")
reverse_reaction.lower_bound = r.upper_bound * -1
reverse_reaction.upper_bound = r.lower_bound * -1
reverse_reaction.objective_coefficient = r.objective_coefficient * -1
reaction_dict = dict([(k, v*-1)
for k, v in r.metabolites.items()])
reverse_reaction.add_metabolites(reaction_dict)
irreve_model.add_reaction(reverse_reaction)
r.upper_bound, r.lower_bound = 0, 0
cobra.manipulation.modify.convert_to_irreversible(irreve_model)
objective_reaction_coefficient_dict = dict([(x.id, x.objective_coefficient)
for x in model.reactions
if x.objective_coefficient])
# this couples the objective reaction to the virtual metabolite
[irreve_model.reactions.get_by_id(k).add_metabolites({objective_metabolite: v})
for k, v in objective_reaction_coefficient_dict.items()]
# print('irregular metabolites: %s' % [(m.id, m._constraint_sense, m._bound)
# for m in irreve_model.metabolites if m._constraint_sense != 'E' or m._bound != 0])
# minimize the sum of fluxes
for r in irreve_model.reactions:
r.objective_coefficient = 1
# print([r.id for r in irreve_model.reactions if r.objective_coefficient != 1])
# print(tolerance_feasibility)
irreve_model.optimize(objective_sense='minimize',
tolerance_feasibility=tolerance_feasibility)
# adjust this to the solution of wt_model
original_flux = model.solution.x_dict
irreve_flux = irreve_model.solution.x_dict
for k in original_flux.keys():
original_flux[k] = irreve_flux[k]
# if reverse reaction exists and its flux is not zero, assign as a negative flux in wt_flux
if k + '_reverse' in irreve_flux.keys() and irreve_flux[k + '_reverse'] != 0:
if irreve_flux[k] != 0:
print('Attention: non-optimal solution')
original_flux[k] = -irreve_flux[k + '_reverse']
model.solution.status = irreve_model.solution.status
model.solution.f = sum([irreve_model.reactions.get_by_id(k).x * v for k, v in
objective_reaction_coefficient_dict.items()])
return model.solution
