def setUp(self):
self._database = DictDatabase()
self._database.set_reaction('rxn_1', parse_reaction('A[e] => B[e]'))
self._database.set_reaction('rxn_2', parse_reaction('B[e] => C[e]'))
self._database.set_reaction('rxn_3', parse_reaction('B[e] => D[e]'))
self._database.set_reaction('rxn_4', parse_reaction('C[e] => E[e]'))
self._database.set_reaction('rxn_5', parse_reaction('D[e] => E[e]'))
self._database.set_reaction('rxn_6', parse_reaction('E[e] =>'))
self._database.set_reaction('ex_A', parse_reaction('A[e] <=>'))
self._mm = MetabolicModel.load_model(self._database,
self._database.reactions)
self._assoc = {
'rxn_1': boolean.Expression('gene_1'),
'rxn_2': boolean.Expression('gene_2 or gene_3'),
'rxn_5': boolean.Expression('gene_3 and gene_4')
}
self._obj_reaction = 'rxn_6'
try:
self._solver = generic.Solver()
except generic.RequirementsError:
self.skipTest('Unable to find an LP solver for tests')
self._prob = fluxanalysis.FluxBalanceProblem(self._mm, self._solver)
def test_get_gene_association(self):
expected_association = {
'rxn_1': boolean.Expression('gene_1 and gene_2'),
'rxn_2': boolean.Expression('gene_3'),
'rxn_4': boolean.Expression('gene_4 and gene_6 and gene_5')
}
self.assertEqual(dict(randomsparse.get_gene_associations(self._model)),
expected_association)
def test_get_rxn_value(self):
mm_irreversible, reversible_gene_assoc, split_rxns =\
gimme.make_irreversible(self._mm, self._assoc,
exclude_list=['ex_A', 'rxn_6'])
f = ['gene\texpression', 'gene_1\t15', 'gene_2\t20',
'gene_3\t15', 'gene_4\t25', 'gene_5\t10', 'gene_6\t25']
d = gimme.parse_transcriptome_file(f, 20)
root_single = gimme.get_rxn_value(boolean.Expression(
reversible_gene_assoc['rxn_1'])._root, d)
self.assertEqual(root_single, 5)
root_and = gimme.get_rxn_value(boolean.Expression(
reversible_gene_assoc['rxn_5'])._root, d)
self.assertEqual(root_and, 10)
root_none = gimme.get_rxn_value(boolean.Expression(
reversible_gene_assoc['rxn_2'])._root, d)
self.assertEqual(root_none, None)
def setUp(self):
self._database = DictDatabase()
self._database.set_reaction('rxn_1', parse_reaction('|A| <=>'))
self._database.set_reaction('rxn_2', parse_reaction('|A| <=> |B|'))
self._database.set_reaction('rxn_3', parse_reaction('|C| <=> |B|'))
self._database.set_reaction('rxn_4', parse_reaction('|C| <=>'))
self._mm = MetabolicModel.load_model(self._database,
self._database.reactions)
self._assoc = {'rxn_2': boolean.Expression('gene_1 or gene_2')}
self._strategy = randomsparse.GeneDeletionStrategy(
self._mm, self._assoc)
def setUp(self):
self.dest = tempfile.mkdtemp()
self.model = NativeModel({
'id': 'test_mode',
'name': 'Test model',
})
# Compounds
self.model.compounds.add_entry(
CompoundEntry({
'id': 'cpd_1',
'formula': Formula.parse('CO2')
}))
self.model.compounds.add_entry(CompoundEntry({
'id': 'cpd_2',
}))
self.model.compounds.add_entry(CompoundEntry({
'id': 'cpd_3',
}))
# Compartments
self.model.compartments.add_entry(CompartmentEntry({'id': 'c'}))
self.model.compartments.add_entry(CompartmentEntry({'id': 'e'}))
# Reactions
self.model.reactions.add_entry(
ReactionEntry({
'id':
'rxn_1',
'equation':
parse_reaction('(2) cpd_1[c] <=> cpd_2[e] + cpd_3[c]'),
'genes':
boolean.Expression('g_1 and (g_2 or g_3)'),
'subsystem':
'Some subsystem'
}))
self.model.reactions.add_entry(
ReactionEntry({
'id':
'rxn_2',
'equation':
parse_reaction(
'(0.234) cpd_1[c] + (1.34) cpd_2[c] => cpd_3[c]'),
'subsystem':
'Biomass'
}))
self.model.biomass_reaction = 'rxn_2'
self.model.limits['rxn_1'] = 'rxn_1', Decimal(-42), Decimal(1000)
self.model.exchange[Compound('cpd_2', 'e')] = (Compound('cpd_2', 'e'),
'EX_cpd_2', -10, 0)
def gene_deletion(model, mm, solver):
genes = {}
gene_assoc = {}
for reaction in model.parse_reactions():
if reaction.genes is None:
continue
expr = boolean.Expression(reaction.genes)
gene_assoc[reaction.id] = expr
for var in expr.variables:
genes.setdefault(var.symbol, set()).add(reaction.id)
p = fluxanalysis.FluxBalanceProblem(mm, solver)
biomass = model.get_biomass_reaction()
p.maximize(biomass)
wt_biomass = p.get_flux(biomass)
#print('Wildtype biomass: {}'.format(wt_biomass))
for gene, reactions in iteritems(genes):
#print('Deleting {}...'.format(gene))
deleted_reactions = set()
for reaction in reactions:
e = gene_assoc[reaction].substitute(lambda v: False
if v.symbol == gene else v)
if e.has_value() and not e.value:
deleted_reactions.add(reaction)
constr = []
for reaction in deleted_reactions:
constr.extend(
p.prob.add_linear_constraints(p.get_flux_var(reaction) == 0))
try:
p.maximize(biomass)
yield gene, p.get_flux(biomass) / wt_biomass
except fluxanalysis.FluxBalanceError:
yield gene, 0.0
finally:
for c in constr:
c.delete()
def gene_deletion(model, mm, solver, algorithm):
genes = {} # Genes -> reaction1, reaction2
gene_assoc = {} # Reaction -> gene1, gene2
# Associate genes with all the reactions
for reaction in model.parse_reactions():
# Ignore anything that doesn't have any genes
if reaction.genes is None:
continue
# Express the genes controling a reaction as the Expression datatype
expr = boolean.Expression(reaction.genes)
# Associates each reaction (reaction.id) with all the genes that control it (expr)
gene_assoc[reaction.id] = expr
# Create a dictionary of each of the genes and all the associated reactions
for var in expr.variables:
genes.setdefault(var.symbol, set()).add(reaction.id)
# Set up the MOMA solver
p = moma.MOMAProblem(mm, solver)
# Get the equation that the solver will use for biomass
biomass = model.get_biomass_reaction()
# Get the wildtype biomass for comparison later
wt_biomass = p.get_fba_biomass(biomass)
# Get the wildtype fluxes that we are going to constrain are model with
wt_fluxes = p.get_fba_flux(biomass)
#wt_biomass = p.get_flux(biomass)
print('Wildtype biomass: {}'.format(wt_biomass))
for gene, reactions in iteritems(genes):
#print('Deleting {}...'.format(gene))
deleted_reactions = set()
# Search through all the reactions and mark each reaction associated with the gene
for reaction in reactions:
e = gene_assoc[reaction].substitute(
lambda v: False if v.symbol == gene else v)
if e.has_value() and not e.value:
deleted_reactions.add(reaction) # Add the reaction to the deleted list
#print(deleted_reactions)
constr = []
# Set all the reactions assiciated to the gene to a flux state of 0
for reaction in deleted_reactions:
constr.extend(p.prob.add_linear_constraints(
p.get_flux_var(reaction) == 0))
#print(constr)
# Test the biomass
try:
if algorithm == "lp2":
p.minimize_lp2(biomass, wt_fluxes)
elif algorithm == "qlp2":
p.minimize_qlp2(biomass, wt_fluxes)
elif algorithm == "lp3":
p.minimize_l1(biomass)
elif algorithm == "qlp3":
p.minimize_l2(biomass)
yield gene, p.get_flux(biomass) / wt_biomass
except moma.MOMAError:
yield gene, -5.0
# Do upon exit
finally:
for c in constr:
c.delete()
