def get_dgf_priors(mi: MaudInput) -> Tuple[pd.Series, pd.DataFrame]:
"""Given a Maud input, get a multivariate prior from equilibrator.
Returns a pandas Series of prior means and a pandas DataFrame of
covariances. Both are indexed by metabolite ids.
:param mi: A MaudInput object
"""
cc = ComponentContribution()
mu = []
sigmas_fin = []
sigmas_inf = []
external_ids = {m.id: m.inchi_key for m in mi.kinetic_model.metabolites}
met_ix = pd.Index(mi.stan_coords.metabolites, name="metabolite")
for met_id in met_ix:
external_id = external_ids[met_id]
if external_id is None:
raise ValueError(f"metabolite {met_id} has no external id.")
c = cc.get_compound(external_id)
if isinstance(c, Compound):
mu_c, sigma_fin_c, sigma_inf_c = cc.standard_dg_formation(c)
mu.append(mu_c)
sigmas_fin.append(sigma_fin_c)
sigmas_inf.append(sigma_inf_c)
else:
raise ValueError(f"cannot find compound for metabolite {met_id}"
f" with external id {external_id}.")
sigmas_fin = np.array(sigmas_fin)
sigmas_inf = np.array(sigmas_inf)
cov = sigmas_fin @ sigmas_fin.T + 1e6 * sigmas_inf @ sigmas_inf.T
return (
pd.Series(mu, index=met_ix, name="prior_mean_dgf").round(10),
pd.DataFrame(cov, index=met_ix, columns=met_ix).round(10),
)
def get_dgf_priors(mi: MaudInput) -> Tuple[pd.Series, pd.DataFrame]:
"""Given a Maud input, get a multivariate prior from equilibrator.
Returns a pandas Series of prior means and a pandas DataFrame of
covariances. Both are indexed by metabolite ids.
:param mi: A MaudInput object
"""
cc = ComponentContribution()
mu = []
sigmas_fin = []
sigmas_inf = []
met_ix = pd.Index(mi.stan_coords.metabolites, name="metabolite")
met_order = [m.id for m in mi.kinetic_model.metabolites]
for m in mi.kinetic_model.metabolites:
external_id = m.id if m.inchi_key is None else m.inchi_key
c = cc.get_compound(external_id)
if isinstance(c, Compound):
mu_c, sigma_fin_c, sigma_inf_c = cc.standard_dg_formation(c)
mu_c += c.transform(
cc.p_h, cc.ionic_strength, cc.temperature, cc.p_mg
).m_as("kJ/mol")
mu.append(mu_c)
sigmas_fin.append(sigma_fin_c)
sigmas_inf.append(sigma_inf_c)
else:
raise ValueError(
f"cannot find compound for metabolite {m.id}"
f" with external id {external_id}."
"\nConsider setting the field metabolite_inchi_key"
" if you haven't already."
)
sigmas_fin = np.array(sigmas_fin)
sigmas_inf = np.array(sigmas_inf)
cov = sigmas_fin @ sigmas_fin.T + 1e6 * sigmas_inf @ sigmas_inf.T
cov = (
pd.DataFrame(cov, index=met_order, columns=met_order)
.loc[met_ix, met_ix]
.round(10)
)
mu = (
pd.Series(mu, index=met_order, name="prior_mean_dgf")
.loc[met_ix]
.round(10)
)
return mu, cov
def runThermo(
pathway: rpPathway,
cc: ComponentContribution=None,
ph: float=DEFAULT_pH,
ionic_strength: float=DEFAULT_ionic_strength,
pMg: float=DEFAULT_pMg,
compound_substitutes: Dict = None,
logger: Logger = getLogger(__name__)
) -> Dict:
"""Given a tar input file, perform thermodynamics analysis for each rpSBML file.
:param inFile: The path to the input file
:param outFile: The path to the output file
:param pathway_id: The id of the heterologous pathway of interest
:param ph: The pH of the host organism (Default: 7.5)
:param ionic_strength: Ionic strenght of the host organism (Default: 0.25M)
:param pMg: The pMg of the host organism (Default: 3.0)
:param temp_k: The temperature of the host organism in Kelvin (Default: 298.15)
:param stdev_factor: The standard deviation factor to calculate MDF (Default: 1.96)
:type pathway: Dict
:type pathway_id: str
:type ph: float
:type ionic_strength: float
:type pMg: float
:type temp_k: float
:type logger: Logger
:rtype: Dict
:return: Pathway updated with thermodynalics values
"""
print_title(
txt='Pathway Reactions',
logger=logger,
waiting=False
)
for rxn in pathway.get_list_of_reactions():
print_reaction(
rxn=rxn,
logger=logger
)
## INTERMEDIATE COMPOUNDS
# Optimise the production of target
# and remove (if possible) intermediate compounds
reactions = remove_compounds(
compounds=pathway.get_intermediate_species(),
reactions=pathway.get_list_of_reactions(),
rxn_target_id=pathway.get_target_rxn_id(),
logger=logger
)
## eQuilibrator
if cc is None:
cc = initThermo(
ph,
ionic_strength,
pMg,
logger
)
# Search for the key ID known by eQuilibrator
cc_species = {}
substituted_species = {}
sep = '__64__'
if compound_substitutes is None:
compound_substitutes = read_compound_substitutes(
os_path.join(
os_path.dirname(os_path.realpath(__file__)),
'data',
'compound_substitutes.csv'
)
)
for spe in pathway.get_species():
spe_split = spe.get_id().split(sep)
if len(spe_split) > 1:
_compound_substitutes = {k+sep+spe_split[1]: v for k, v in compound_substitutes.items()}
else:
_compound_substitutes = deepcopy(compound_substitutes)
# If the specie is listed in substitutes file, then take search values from it
# Check if starts with in case of compound names are like CMPD_NAME__64__COMPID
if spe.get_id() in _compound_substitutes:
cc_species[spe.get_id()] = search_equilibrator_compound(
cc=cc,
id=_compound_substitutes[spe.get_id()]['id'],
inchikey=_compound_substitutes[spe.get_id()]['inchikey'],
inchi=_compound_substitutes[spe.get_id()]['inchi'],
logger=logger
)
# Else, take search values from rpCompound
else:
cc_species[spe.get_id()] = search_equilibrator_compound(
cc=cc,
id=spe.get_id(),
inchikey=spe.get_inchikey(),
inchi=spe.get_inchi(),
smiles=spe.get_smiles(),
logger=logger
)
if cc_species[spe.get_id()] != {}:
if spe.get_id() != cc_species[spe.get_id()]['id']:
substituted_species[spe.get_id()] = cc_species[spe.get_id()][cc_species[spe.get_id()]['cc_key']]
else:
logger.warning(f'Compound {spe.get_id()} has not been found within eQuilibrator cache')
# Store thermo values for the net reactions
# and for each of the reactions within the pathway
results = {
'net_reaction': {},
'optimized_net_reaction': Reaction.sum_stoichio(reactions),
'reactions': {},
'optimized_reactions': {
rxn.get_id(): rxn
for rxn in reactions
},
'species': {},
'substituted_species': substituted_species
}
# Get the formation energy for each compound
for spe_id, cc_spe in cc_species.items():
try:
value = cc.standard_dg_formation(
cc.get_compound(
cc_spe[cc_spe['cc_key']]
)
)[0] # get .mu
except Exception as e:
value = None
logger.debug(e)
if value is None:
value = 'NaN'
results['species'][spe_id] = {
'standard_dg_formation': {
'value': value,
'units': 'kilojoule / mole'
}
}
# Build the list of IDs known by eQuilibrator
species_cc_ids = {}
for spe_id, cc_spe in cc_species.items():
if cc_spe == {}:
species_cc_ids[spe_id] = spe_id
else:
species_cc_ids[spe_id] = cc_spe[cc_spe['cc_key']]
## REACTIONS
# Compute thermo for each reaction
for rxn in pathway.get_list_of_reactions():
results['reactions'][rxn.get_id()] = eQuilibrator(
species_stoichio=rxn.get_species(),
species_ids=species_cc_ids,
cc=cc,
logger=logger
)
## THERMO
print_title(
txt='Computing thermodynamics (eQuilibrator)...',
logger=logger,
waiting=True
)
results['net_reaction'] = eQuilibrator(
species_stoichio=Reaction.sum_stoichio(reactions),
species_ids=species_cc_ids,
cc=cc,
logger=logger
)
print_OK(logger)
# Write results into the pathway
write_results_to_pathway(pathway, results, logger)
return results
class Thermodynamics:
"""Class to calculate thermodynamics of Pickaxe runs.
Thermodynamics allows for the calculation of:
1) Standard ∆G' of formation
2) Standard ∆G'o of reaction
3) Physiological ∆G'm of reaction
4) Adjusted ∆G' of reaction
eQuilibrator objects can also be obtained from r_ids and c_ids.
Parameters
----------
mongo_uri: str
URI of the mongo database.
client: MongoClient
Connection to Mongo.
CC: ComponentContribution
eQuilibrator Component Contribution object to calculate ∆G with.
lc: LocalCompoundCache
The local compound cache to generate eQuilibrator compounds from.
"""
def __init__(
self,
):
# Mongo params
self.mongo_uri = None
self.client = None
self._core = None
# eQ params
self.CC = ComponentContribution()
self.lc = None
self._water = None
def load_mongo(self, mongo_uri: Union[str, None] = None):
if mongo_uri:
self.mongo_uri = mongo_uri
self.client = MongoClient(mongo_uri)
else:
self.mongo_uri = "localhost:27017"
self.client = MongoClient()
self._core = self.client["core"]
def _all_dbs_loaded(self):
if self.client and self._core and self.lc:
return True
else:
print("Load connection to Mongo and eQuilibrator local cache.")
return False
def _eq_loaded(self):
if self.lc:
return True
else:
print("Load eQulibrator local cache.")
return False
def _reset_CC(self):
"""reset CC back to defaults"""
self.CC.p_h = default_physiological_p_h
self.CC.p_mg = default_physiological_p_mg
self.CC.temperature = default_physiological_temperature
self.CC.ionic_strength = default_physiological_ionic_strength
def load_thermo_from_postgres(
self, postgres_uri: str = "postgresql:///eq_compounds"
) -> None:
"""Load a LocalCompoundCache from a postgres uri for equilibrator.
Parameters
----------
postgres_uri : str, optional
uri of the postgres DB to use, by default "postgresql:///eq_compounds"
"""
self.lc = LocalCompoundCache()
self.lc.ccache = CompoundCache(create_engine(postgres_uri))
self._water = self.lc.get_compounds("O")
def load_thermo_from_sqlite(
self, sqlite_filename: str = "compounds.sqlite"
) -> None:
"""Load a LocalCompoundCache from a sqlite file for equilibrator.
compounds.sqlite can be generated through LocalCompoundCache's method
generate_local_cache_from_default_zenodo
Parameters
----------
sqlite_filename: str
filename of the sqlite file to load.
"""
self.lc = LocalCompoundCache()
self.lc.load_cache(sqlite_filename)
self._water = self.lc.get_compounds("O")
def get_eQ_compound_from_cid(
self, c_id: str, pickaxe: Pickaxe = None, db_name: str = None
) -> Union[Compound, None]:
"""Get an equilibrator compound for a given c_id from the core.
Attempts to retrieve a compound from the core or a specified db_name.
Parameters
----------
c_id : str
compound ID for MongoDB lookup of a compound.
pickaxe : Pickaxe
pickaxe object to look for the compound in, by default None.
db_name : str
Database to look for compound in before core database, by default None.
Returns
-------
equilibrator_assets.compounds.Compound
eQuilibrator Compound
"""
# Find locally in pickaxe
compound_smiles = None
if pickaxe:
if c_id in pickaxe.compounds:
compound_smiles = pickaxe.compounds[c_id]["SMILES"]
else:
return None
# Find in mongo db
elif self._all_dbs_loaded():
if db_name:
compound = self.client[db_name].compounds.find_one(
{"_id": c_id}, {"SMILES": 1}
)
if compound:
compound_smiles = compound["SMILES"]
# No cpd smiles from database name
if not compound_smiles:
compound = self._core.compounds.find_one({"_id": c_id}, {"SMILES": 1})
if compound:
compound_smiles = compound["SMILES"]
# No compound_smiles at all
if not compound_smiles or "*" in compound_smiles:
return None
else:
eQ_compound = self.lc.get_compounds(
compound_smiles, bypass_chemaxon=True, save_empty_compounds=True
)
return eQ_compound
def standard_dg_formation_from_cid(
self, c_id: str, pickaxe: Pickaxe = None, db_name: str = None
) -> Union[float, None]:
"""Get standard ∆Gfo for a compound.
Parameters
----------
c_id : str
Compound ID to get the ∆Gf for.
pickaxe : Pickaxe
pickaxe object to look for the compound in, by default None.
db_name : str
Database to look for compound in before core database, by default None.
Returns
-------
Union[float, None]
∆Gf'o for a compound, or None if unavailable.
"""
eQ_cpd = self.get_eQ_compound_from_cid(c_id, pickaxe, db_name)
if not eQ_cpd:
return None
dgf = self.CC.standard_dg_formation(eQ_cpd)
dgf = dgf[0]
return dgf
def get_eQ_reaction_from_rid(
self, r_id: str, pickaxe: Pickaxe = None, db_name: str = None
) -> Union[PhasedReaction, None]:
"""Get an eQuilibrator reaction object from an r_id.
Parameters
----------
r_id : str
Reaction id to get object for.
pickaxe : Pickaxe
pickaxe object to look for the compound in, by default None.
db_name : str
Database to look for reaction in.
Returns
-------
PhasedReaction
eQuilibrator reactiono to calculate ∆Gr with.
"""
if pickaxe:
if r_id in pickaxe.reactions:
reaction_info = pickaxe.reactions[r_id]
else:
return None
elif db_name:
mine = self.client[db_name]
reaction_info = mine.reactions.find_one({"_id": r_id})
if not reaction_info:
return None
else:
return None
reactants = reaction_info["Reactants"]
products = reaction_info["Products"]
lhs = " + ".join(f"{r[0]} {r[1]}" for r in reactants)
rhs = " + ".join(f"{p[0]} {p[1]}" for p in products)
reaction_string = " => ".join([lhs, rhs])
compounds = set([r[1] for r in reactants])
compounds.update(tuple(p[1] for p in products))
eQ_compound_dict = {
c_id: self.get_eQ_compound_from_cid(c_id, pickaxe, db_name)
for c_id in compounds
}
if not all(eQ_compound_dict.values()):
return None
if "X73bc8ef21db580aefe4dbc0af17d4013961d9d17" not in compounds:
eQ_compound_dict["water"] = self._water
eq_reaction = Reaction.parse_formula(eQ_compound_dict.get, reaction_string)
return eq_reaction
def physiological_dg_prime_from_rid(
self, r_id: str, pickaxe: Pickaxe = None, db_name: str = None
) -> Union[pint.Measurement, None]:
"""Calculate the ∆Gm' of a reaction.
Parameters
----------
r_id : str
ID of the reaction to calculate.
pickaxe : Pickaxe
pickaxe object to look for the compound in, by default None.
db_name : str
MINE the reaction is found in.
Returns
-------
pint.Measurement
The calculated ∆G'm.
"""
eQ_reaction = self.get_eQ_reaction_from_rid(r_id, pickaxe, db_name)
if not eQ_reaction:
return None
dGm_prime = self.CC.physiological_dg_prime(eQ_reaction)
return dGm_prime
def standard_dg_prime_from_rid(
self, r_id: str, pickaxe: Pickaxe = None, db_name: str = None
) -> Union[pint.Measurement, None]:
"""Calculate the ∆G'o of a reaction.
Parameters
----------
r_id : str
ID of the reaction to calculate.
pickaxe : Pickaxe
pickaxe object to look for the compound in, by default None.
db_name : str
MINE the reaction is found in.
Returns
-------
pint.Measurement
The calculated ∆G'o.
"""
eQ_reaction = self.get_eQ_reaction_from_rid(r_id, pickaxe, db_name)
if not eQ_reaction:
return None
dG0_prime = self.CC.standard_dg_prime(eQ_reaction)
return dG0_prime
def dg_prime_from_rid(
self,
r_id: str,
pickaxe: Pickaxe = None,
db_name: str = None,
p_h: Q_ = default_physiological_p_h,
p_mg: Q_ = default_physiological_p_mg,
ionic_strength: Q_ = default_physiological_ionic_strength,
) -> Union[pint.Measurement, None]:
"""Calculate the ∆G' of a reaction.
Parameters
----------
r_id : str
ID of the reaction to calculate.
pickaxe : Pickaxe
pickaxe object to look for the compound in, by default None.
db_name : str
MINE the reaction is found in.
p_h : Q_
pH of system.
p_mg: Q_
pMg of the system.
ionic_strength: Q_
ionic strength of the system.
Returns
-------
pint.Measurement
The calculated ∆G'.
"""
eQ_reaction = self.get_eQ_reaction_from_rid(r_id, pickaxe, db_name)
if not eQ_reaction:
return None
self.CC.p_h = p_h
self.CC.p_mg = p_mg
self.CC.ionic_strength = ionic_strength
dG_prime = self.CC.dg_prime(eQ_reaction)
self._reset_CC()
return dG_prime