def crossover(community, sol, fluxes=False, pfba=False):
"""Get the crossover solution."""
gcs = sol.members.growth_rate.drop("medium")
com_growth = sol.growth_rate
logger.info("Starting crossover...")
with community as com:
logger.info("constraining growth rates.")
context = get_context(community)
if context is not None:
context(partial(reset_min_community_growth, com))
reset_min_community_growth(com)
com.variables.community_objective.lb = 0.0
com.variables.community_objective.ub = com_growth + 1e-6
com.objective = 1000.0 * com.variables.community_objective
for sp in com.species:
const = com.constraints["objective_" + sp]
const.ub = gcs[sp]
logger.info("finding closest feasible solution")
s = com.optimize()
if s is None:
reset_solver(com)
s = com.optimize()
if s is not None:
s = CommunitySolution(com, slim=not fluxes)
for sp in com.species:
com.constraints["objective_" + sp].ub = None
if s is None:
raise OptimizationError("crossover could not converge (status = %s)." %
community.solver.status)
s.objective_value /= 1000.0
return s
def elasticities(com, fraction=0.5, reactions=None, progress=True):
"""Calculate elasticities for reactions.
Calculates elasticity coefficients using the specified reactions as
response and exchange bounds (diet) and taxa abundances as
effectors/parameters. Will use an arbitrary flux distribution as base.
Arguments
---------
com : micom.Community
The community for wrhich to calculate elasticities.
fraction : double
The tradeoff to use for the cooperative tradeoff method. Fraction of
maximal community growth to enforce.
reactions : iterable
A list of reactions to get elasticities for. Elements can either be
reactions from the model, strings specifying the ids of reactions
or ints specifying the indices of reactions. Defaults to using all
reactions.
progress : boolean
Whether to shwo progress bars. Will show two, one for the diet
optimizations and another one for the taxa abundances.
Returns
-------
pandas.DataFrame
A data frame with the following columns:
"reaction" - the exchange reaction (response),
"taxon" - the taxon the reaction is from,
"effector" - the parameter that was changed,
"direction" - whether the flux runs in the forward or reverse
direction,
"elasticity" - the elasticity coefficient,
"type" - the type of effector either "exchange" for diet or "abundance"
for taxa abundances.
"""
growth_rate = None
if reactions is None:
reactions = com.reactions
reactions = com.reactions.get_by_any(reactions)
with com:
context = get_context(com)
context(partial(reset_min_community_growth, com))
by_medium = elasticities_by_medium(
com, reactions, fraction, growth_rate, progress
)
by_medium["type"] = "exchanges"
by_abundance = elasticities_by_abundance(
com, reactions, fraction, growth_rate, progress
)
by_abundance["type"] = "abundance"
both = pd.concat([by_medium, by_abundance]).reset_index(drop=True)
both.loc[both.taxon == "m", "taxon"] = "medium"
return both
def knock_out_metabolite(metabolite, force_steady_state=False):
"""'Knockout' a metabolite. This can be done in 2 ways:
1. Implementation follows the description in [1] "All fluxes around
the metabolite M should be restricted to only produce the
metabolite, for which balancing constraint of mass conservation is
relaxed to allow nonzero values of the incoming fluxes whereas all
outgoing fluxes are limited to zero."
2. Force steady state All reactions consuming the metabolite are
restricted to only produce the metabolite. A demand reaction is
added to sink the metabolite produced to keep the problem feasible
under the S.v = 0 constraint.
Knocking out a metabolite overrules the constraints set on the
reactions producing the metabolite.
Parameters
----------
force_steady_state: bool
If True, uses approach 2.
References
----------
.. [1] Kim, P.-J., Lee, D.-Y., Kim, T. Y., Lee, K. H., Jeong, H.,
Lee, S. Y., & Park, S. (2007). Metabolite essentiality elucidates
robustness of Escherichia coli metabolism. PNAS, 104(34), 13638-13642
"""
# restrict reactions to produce metabolite
for rxn in metabolite.reactions:
if rxn.metabolites[metabolite] > 0:
rxn.bounds = (0, 0) if rxn.upper_bound < 0 \
else (0, rxn.upper_bound)
elif rxn.metabolites[metabolite] < 0:
rxn.bounds = (0, 0) if rxn.lower_bound > 0 \
else (rxn.lower_bound, 0)
if force_steady_state:
metabolite._model.add_boundary(metabolite,
type="knock-out",
lb=0,
ub=1000,
reaction_id="KO_{}".format(
metabolite.id))
else:
previous_bounds = metabolite.constraint.lb, metabolite.constraint.ub
metabolite.constraint.lb, metabolite.constraint.ub = -1000, 1000
context = get_context(metabolite)
if context:
def reset():
metabolite.constraint.lb, metabolite.constraint.ub = previous_bounds
context(reset)
def test_get_context(model: "Model") -> None:
"""Test if context retrieval is working."""
with model as model:
# reverse optimization direcion
model.objective_direction = "min"
# retrieve context
context = get_context(model)
# check size of the context
if context:
assert context.size() == 1
# there shouldn't be any history
if context:
assert context.size() == 0
def exchange_elasticities(com, fraction=1.0, progress=True):
"""Calculate elasticities for exchange reactions.
Calculates elasticity coefficients using the exchange reactions as
response and exchange bounds (diet) and taxa abundances as
effectors/parameters. Will use an arbitrary flux distribution as base.
Arguments
---------
com : micom.Community
The community for wrhich to calculate elasticities.
fraction : double
The tradeoff to use for the cooperative tradeoff method. Fraction of
maximal community growth to enforce.
progress : boolean
Whether to shwo progress bars. Will show two, one for the diet
optimizations and another one for the taxa abundances.
Returns
-------
pandas.DataFrame
A data frame with the following columns:
"reaction" - the exchange reaction (response),
"effector" - the parameter that was changed,
"direction" - whether the flux runs in the forward od reverse direction,
"elasticity" - the elasticity coefficient,
"type" - the type of effector either "exchange" for diet or "abundance"
for taxa abundances.
"""
growth_rate = None
with com:
context = get_context(com)
context(partial(reset_min_community_growth, com))
rxns = com.exchanges
by_medium = elasticities_by_medium(com, rxns, fraction, growth_rate,
progress)
by_medium["type"] = "exchanges"
by_abundance = elasticities_by_abundance(com, rxns, fraction,
growth_rate, progress)
by_abundance["type"] = "abundance"
return pd.concat([by_medium, by_abundance])
def minimal_medium(
community,
community_growth,
exchanges=None,
min_growth=0.0,
exports=False,
minimize_components=False,
open_exchanges=False,
solution=False,
):
"""Find the minimal growth medium for the community.
Finds the minimal growth medium for the community which allows for
community as well as individual growth. Here, a minimal medium can either
be the medium requiring the smallest total import flux or the medium
requiring the least components (ergo ingredients).
Arguments
---------
community : micom.Community
The community to modify.
community_growth : positive float
The minimum community-wide growth rate.
exchanges : list of cobra.Reactions
The list of exchange reactions that are penalized.
min_growth : positive float or array-like object.
The minimum growth rate for each individual in the community. Either
a single value applied to all individuals or one value for each.
exports : boolean
Whether to include export fluxes in the returned medium. Defaults to
False which will only return import fluxes.
minimize_components : boolean
Whether to minimize the number of components instead of the total
import flux. Might be more intuitive if set to True but may also be
slow to calculate for large communities.
open_exchanges : boolean or number
Whether to ignore currently set bounds and make all exchange reactions
in the model possible. If set to a number all exchange reactions will
be opened with (-number, number) as bounds.
solution : boolean
Whether to also return the entire solution and all fluxes for the
minimal medium.
Returns
-------
pandas.Series or dict
A series {rid: flux} giving the import flux for each required import
reaction. If `solution` is True retuns a dictionary
{"medium": panas.Series, "solution": micom.CommunitySolution}.
"""
logger.info("calculating minimal medium for %s" % community.id)
boundary_rxns = community.exchanges
if isinstance(open_exchanges, bool):
open_bound = 1000
else:
open_bound = open_exchanges
min_growth = _format_min_growth(min_growth, community.species)
with community as com:
if open_exchanges:
logger.info("opening exchanges for %d imports" %
len(boundary_rxns))
for rxn in boundary_rxns:
rxn.bounds = (-open_bound, open_bound)
logger.info("applying growth rate constraints")
context = get_context(community)
if context is not None:
context(partial(reset_min_community_growth, com))
com.variables.community_objective.lb = community_growth
_apply_min_growth(community, min_growth)
com.objective = Zero
logger.info("adding new media objective")
if minimize_components:
add_mip_obj(com, boundary_rxns)
else:
add_linear_obj(com, boundary_rxns)
sol = com.optimize(fluxes=True, pfba=False)
if sol is None:
logger.warning("minimization of medium was unsuccessful")
return None
logger.info("formatting medium")
medium = pd.Series()
tol = community.solver.configuration.tolerances.feasibility
for rxn in boundary_rxns:
export = len(rxn.reactants) == 1
flux = sol.fluxes.loc["medium", rxn.id]
if abs(flux) < tol:
continue
if export:
medium[rxn.id] = -flux
elif not export:
medium[rxn.id] = flux
if not exports:
medium = medium[medium > 0]
if solution:
return {"medium": medium, "solution": sol}
else:
return medium
