-def create_community_model_with_balanced_growth(community: Community, growth_rate: float) ‑> cobra.core.model.Model
+def create_community_model_with_balanced_growth(community: Community, growth_rate: float, organism_exchange_bounds: Dict[str, Tuple[float, float]] = {}) ‑> cobra.core.model.Model
Creates a combined community model with an stoichiometric-matrix-integrated balanced growth approach.
@@ -888,7 +928,12 @@The principle used herein also means that if another growth rate is to be tested, a new model has to be generated for this specific growth rate.
@@ -898,14 +943,17 @@def create_community_model_with_balanced_growth(community: Community, growth_rate: float) -> cobra.Model:
+def create_community_model_with_balanced_growth(community: Community, growth_rate: float, organism_exchange_bounds: Dict[str, Tuple[float, float]] = {}) -> cobra.Model:
"""Creates a combined community model with an stoichiometric-matrix-integrated balanced growth approach.
Description
@@ -964,6 +1012,11 @@ Arguments
metabolites from the respective SingleSpecies instances, as well as from the exchange
compartment to the environment for all input/output metabolites of the Community instance. All previous standard
exchanges of the single models (usually starting with "EX_") are deleted.
+ The new exchange reactions start with EXCHG_in_ for input reactions (input to organism) and EXCHG_out_ for output metabolites
+ (output from organism). Both types of EXCHG_ reactions are irreversible, and EXCHG_in_ reactions get an upper bound of
+ 1000 mmol/(gDW*h) as standard in order to enforce the incorporation of Msnake_UPPER_ upper bound metabolites so that growth is
+ actually enforced for all organisms in which reactions occur (which may not be the case if reactions with lower/upper bounds
+ of inf are used).
The principle used herein also means that if another growth rate is to be tested, a new model has to be generated for this
specific growth rate.
@@ -976,8 +1029,11 @@ Arguments
Arguments
----------
- * community: Community ~
- * growth_rate: float ~
+ * community: Community ~ A CommModelPy Community instance.
+ * growth_rate: float ~ The growth rate to which the community shall be fixed.
+ * organism_exchange_bounds: Dict[Tuple[float, float]] ~ A dictionary containing reaction IDs
+ (which may also include the EXCHG_ reactions introduced by this function) as keys
+ and, in the float tuple at index 0 a set lower bound and at index 1 a set upper bound.
"""
# Get number of SingleModel instances in Community instance
num_single_models = len(community.single_models)
@@ -1078,15 +1134,86 @@ Arguments
community_biomass_metabolite: -1,
})
- # Add minimal and maximal bound constraint
+ # Add single species <-> exchange compartment exchanges
+ for single_model in community.single_models:
+ exchange_metabolite_ids = list(
+ set(single_model.input_metabolite_ids + single_model.output_metabolite_ids))
+ exchange_metabolite_ids = [
+ x+"_"+single_model.species_abbreviation for x in exchange_metabolite_ids]
+
+ for exchange_metabolite_id in exchange_metabolite_ids:
+ single_model_base_metabolite_id = exchange_metabolite_id.replace("_"+single_model.species_abbreviation, "")
+ exchange_compartment_metabolite_id = single_model.model_metabolite_to_exchange_id_mapping[single_model_base_metabolite_id]
+
+ # Add metabolites to reaction
+ try:
+ internal_metabolite = merged_model.metabolites.get_by_id(
+ exchange_metabolite_id)
+ except:
+ print("ERROR: Internal exchange metabolite ID " + exchange_metabolite_id + "does not exist!")
+ species_exchange_metabolite_id = exchange_compartment_metabolite_id+"_"+community.exchange_compartment_id
+ try:
+ exchange_compartment_metabolite = merged_model.metabolites.get_by_id(
+ species_exchange_metabolite_id)
+ except:
+ new_species_exchange_metabolite = cobra.Metabolite(id=species_exchange_metabolite_id,
+ compartment="exchg")
+ merged_model.add_metabolites(new_species_exchange_metabolite)
+ exchange_compartment_metabolite = merged_model.metabolites.get_by_id(
+ species_exchange_metabolite_id)
+
+ # Set reaction bounds
+ is_input = single_model_base_metabolite_id in single_model.input_metabolite_ids
+ is_output = single_model_base_metabolite_id in single_model.output_metabolite_ids
+
+ # Set reaction instance
+ if is_input:
+ reaction_in = cobra.Reaction(id="EXCHG_in_"+single_model.species_abbreviation+"_"+exchange_metabolite_id.replace("_"+single_model.species_abbreviation, "")+"_to_"+exchange_compartment_metabolite_id,
+ name=f"Input exchange for {exchange_metabolite_id} from single species {single_model.species_abbreviation} to exchange compartment")
+ reaction_in.add_metabolites({
+ exchange_compartment_metabolite: -1,
+ internal_metabolite: 1,
+ })
+ reaction_in.lower_bound = 0
+ reaction_in.upper_bound = 1000
+
+ merged_model.add_reactions([reaction_in])
+ if is_output:
+ reaction_out = cobra.Reaction(id="EXCHG_out_"+single_model.species_abbreviation+"_"+exchange_metabolite_id.replace("_"+single_model.species_abbreviation, "")+"_to_"+exchange_compartment_metabolite_id,
+ name=f"Output exchange for {exchange_metabolite_id} from single species {single_model.species_abbreviation} to exchange compartment")
+ reaction_out.add_metabolites({
+ internal_metabolite: -1,
+ exchange_compartment_metabolite: 1,
+ })
+ reaction_out.lower_bound = 0
+ reaction_out.upper_bound = float("inf")
+
+ merged_model.add_reactions([reaction_out])
+
+ # Add organism-specific reaction bounds
+ bound_reaction_ids = [x.id for x in merged_model.reactions
+ if x.id in list(organism_exchange_bounds.keys())]
+ for bound_reaction_id in bound_reaction_ids:
+ lower_bound = organism_exchange_bounds[bound_reaction_id][0]
+ upper_bound = organism_exchange_bounds[bound_reaction_id][1]
+ reaction = merged_model.reactions.get_by_id(bound_reaction_id)
+ reaction.lower_bound = lower_bound
+ reaction.upper_bound = upper_bound
+
+ # Add minimal and maximal bound constraints using pseudo-metabolites and pseudo-reactions
reaction_ids = [x.id for x in merged_model.reactions]
for reaction_id in reaction_ids:
reaction = merged_model.reactions.get_by_id(reaction_id)
# Check organism ID
- reaction_organism_id = reaction.id.split("_")[-1]
- if reaction_organism_id not in organism_id_biomass_reaction_id_mapping.keys():
- continue
+ if reaction_id.startswith("EXCHG"):
+ reaction_organism_id = reaction.id.split("_")[2]
+ if reaction_organism_id not in organism_id_biomass_reaction_id_mapping.keys():
+ continue
+ else:
+ reaction_organism_id = reaction.id.split("_")[-1]
+ if reaction_organism_id not in organism_id_biomass_reaction_id_mapping.keys():
+ continue
organism_biomass_reaction = merged_model.reactions.get_by_id(
organism_id_biomass_reaction_id_mapping[reaction_organism_id])
@@ -1099,6 +1226,7 @@ Arguments
# Add ~r
new_reaction = cobra.Reaction(id="Rsnake_UPPER_"+reaction.id,
name="Delivery reaction of upper bound enforcing metabolite for "+reaction.id)
+
# Add ~M to original reaction
reaction.add_metabolites({
new_metabolite: 1,
@@ -1111,6 +1239,8 @@ Arguments
})
merged_model.add_reactions([new_reaction])
+ reaction.upper_bound = float("inf")
+
# Add minimal bound constraint
if (reaction.lower_bound != -float("inf")) and (reaction.lower_bound != 0.0):
# Add ~M
@@ -1119,7 +1249,8 @@ Arguments
compartment="exchg")
# Add ~r
new_reaction = cobra.Reaction(id="Rsnake_LOWER_"+reaction.id,
- name="Delivery reaction of lower bound enforcing metabolite for "+reaction.id)
+ name="Consuming reaction of lower bound enforcing metabolite for "+reaction.id)
+
# Add ~M to original reaction
reaction.add_metabolites({
new_metabolite: 1,
@@ -1132,53 +1263,10 @@ Arguments
})
merged_model.add_reactions([new_reaction])
- # Add single species <-> exchange compartment exchanges
- for single_model in community.single_models:
- exchange_metabolite_ids = list(
- set(single_model.input_metabolite_ids + single_model.output_metabolite_ids))
- exchange_metabolite_ids = [
- x+"_"+single_model.species_abbreviation for x in exchange_metabolite_ids]
-
- # Add mock community biomass metabolites for the ASTHERISC package's species recognition
- biomass_metabolite = cobra.Metabolite(id="community_biomass_"+single_model.species_abbreviation,
- name="Mock community biomass metabolite for ASTHERISC package species recognition",
- compartment="exchg")
- merged_model.add_metabolites([biomass_metabolite])
-
- for exchange_metabolite_id in exchange_metabolite_ids:
- exchange_compartment_metabolite_id = single_model.model_metabolite_to_exchange_id_mapping[exchange_metabolite_id.replace(
- "_"+single_model.species_abbreviation, "")]
-
- # Set reaction instance
- reaction = cobra.Reaction(id="EXCHG_"+single_model.species_abbreviation+"_"+exchange_metabolite_id.replace("_"+single_model.species_abbreviation, "")+"_to_"+exchange_compartment_metabolite_id,
- name=f"Exchange for {exchange_metabolite_id} from single species {single_model.species_abbreviation} to exchange compartment")
-
- # Set reaction bounds
- is_input = exchange_compartment_metabolite_id in community.input_metabolite_ids
- if is_input:
- reaction.lower_bound = -float("inf")
- else:
- reaction.lower_bound = 0
- is_output = exchange_compartment_metabolite_id in community.output_metabolite_ids
- if is_output:
- reaction.upper_bound = float("inf")
- else:
- reaction.upper_bound = 0
-
- # Add metabolites to reaction
- internal_metabolite = merged_model.metabolites.get_by_id(
- exchange_metabolite_id)
- exchange_compartment_metabolite = merged_model.metabolites.get_by_id(
- exchange_compartment_metabolite_id+"_"+community.exchange_compartment_id)
- reaction.add_metabolites({
- internal_metabolite: -1,
- exchange_compartment_metabolite: 1,
- })
-
- # Add reaction to model
- merged_model.add_reactions([reaction])
+ reaction.lower_bound = 0
# Set merged model's objective to community biomass
+ merged_model.add_reactions([community_biomass_reaction])
merged_model.objective = "COMMUNITY_BIOMASS"
return merged_model
@@ -1530,7 +1618,7 @@ Usage Example
set the prefix of the community's exchange metabolites to "EX_C" and E. coli has the
input metabolites glc__D, o2, h and h2o, and V. natriegens the additional input
metabolite biotin, and both habe the output metabolites ac and co2,
-then we could set the Community instance as follows:
+then we could set the Community instance as follows:
community_example = Community(
single_models = [ecoli_core, vnatriegens_core],
@@ -1539,7 +1627,7 @@ Usage Example
input_metabolite_ids = ["glc__D", "o2", "h", "h2o", "ac", "biotin"],
output_metabolite_ids = ["ac", "co2"]
)
-
+Suppose we defined a BiGG-compliant core model of E. coli, and we set the exchange compartment metabolite names just as the metabolite IDs themselves without the addition of the underscore plus compartment name, then -a SingleModel definition could look like this: +a SingleModel definition could look like this:
single_ec_core_model = SingleModel(
cobra_model=e_coli_core_model,
@@ -1679,7 +1767,7 @@ Usage Example
"ac_e": "ac",
}
)
-
+