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)
