def find_metabolites_consumed_with_closed_bounds(model):
"""
Return metabolites that can be consumed when boundary reactions are closed.
Reverse case from 'find_metabolites_produced_with_closed_bounds', just
like metabolites should not be produced from nothing, mass should not
simply be removed from the model.
Parameters
----------
model : cobra.Model
The metabolic model under investigation.
"""
mets_consumed = list()
helpers.close_boundaries_sensibly(model)
for met in model.metabolites:
with model:
exch = model.add_boundary(met,
type='irrex',
reaction_id='IRREX',
lb=-1,
ub=0)
if helpers.run_fba(model, exch.id, direction='min') < 0:
mets_consumed.append(met)
return mets_consumed
def find_metabolites_not_consumed_with_open_bounds(model):
"""
Return metabolites that cannot be consumed with open boundary reactions.
Reverse case from 'find_metabolites_not_produced_with_open_bounds', just
like metabolites should all be produced with open exchanges, they should
also all be consumed with open exchanges.
Parameters
----------
model : cobra.Model
The metabolic model under investigation.
"""
mets_not_consumed = list()
helpers.open_boundaries(model)
for met in model.metabolites:
with model:
exch = model.add_boundary(met,
type="irrex",
reaction_id="IRREX",
lb=-1,
ub=0)
solution = helpers.run_fba(model, exch.id, direction="min")
if solution is np.nan or solution == 0:
mets_not_consumed.append(met)
return mets_not_consumed
def find_blocked_biomass_precursors(reaction, model):
"""
Return a list of all biomass precursors that cannot be produced.
Parameters
----------
reaction : cobra.core.reaction.Reaction
The biomass reaction of the model under investigation.
model : cobra.Model
The metabolic model under investigation.
Returns
-------
list
Metabolite objects that are reactants of the biomass reaction excluding
ATP and H2O that cannot be produced by flux balance analysis.
"""
LOGGER.debug("Finding blocked biomass precursors")
precursors = find_biomass_precursors(model, reaction)
blocked_precursors = list()
_, ub = helpers.find_bounds(model)
for precursor in precursors:
with model:
dm_rxn = model.add_boundary(precursor,
type="safe-demand",
reaction_id="safe_demand",
lb=0,
ub=ub)
flux = helpers.run_fba(model, dm_rxn.id, direction='max')
if np.isnan(flux) or abs(flux) < 1E-08:
blocked_precursors.append(precursor)
return blocked_precursors
def find_blocked_biomass_precursors(reaction, model):
"""
Return a list of all biomass precursors that cannot be produced.
Parameters
----------
reaction : cobra.core.reaction.Reaction
The biomass reaction of the model under investigation.
model : cobra.Model
The metabolic model under investigation.
Returns
-------
list
Metabolite objects that are reactants of the biomass reaction excluding
ATP and H2O that cannot be produced by flux balance analysis.
"""
LOGGER.debug("Finding blocked biomass precursors")
precursors = find_biomass_precursors(model, reaction)
blocked_precursors = list()
_, ub = helpers.find_bounds(model)
for precursor in precursors:
with model:
dm_rxn = model.add_boundary(
precursor,
type="safe-demand",
reaction_id="safe_demand",
lb=0,
ub=ub
)
flux = helpers.run_fba(model, dm_rxn.id, direction='max')
if np.isnan(flux) or abs(flux) < 1E-08:
blocked_precursors.append(precursor)
return blocked_precursors
def test_biomass_default_production(model, reaction_id):
"""
Expect biomass production in default medium.
Using flux balance analysis this test optimizes the model for growth in
the medium that is set by default. Any non-zero growth rate is accepted to
pass this test.
"""
ann = test_biomass_default_production.annotation
ann["data"][reaction_id] = helpers.run_fba(model, reaction_id)
ann["message"][reaction_id] = wrapper.fill(
"""Using the biomass reaction {} this is the growth rate that can be
achieved when the model is simulated on the provided default medium: {}
""".format(reaction_id, ann["data"][reaction_id]))
assert ann["data"][reaction_id] > 0.0, ann["message"][reaction_id]
def test_fast_growth_default(model, reaction_id):
"""
Expect the predicted growth rate for each BOF to be below 10.3972.
The growth rate of a metabolic model should not be faster than that of the
fastest growing organism. This is based on lowest doubling time reported
here:
http://www.pnnl.gov/science/highlights/highlight.asp?id=879
"""
ann = test_fast_growth_default.annotation
ann["data"][reaction_id] = helpers.run_fba(model, reaction_id)
ann["message"][reaction_id] = wrapper.fill(
"""Using the biomass reaction {} and when the model is simulated on
the provided default medium the growth rate amounts to {}""".format(
reaction_id, ann["data"][reaction_id]))
assert ann["data"][reaction_id] <= 10.3972, ann["message"][reaction_id]
def test_biomass_open_production(model, reaction_id):
"""
Expect biomass production in complete medium.
Using flux balance analysis this test optimizes the model for growth using
a complete medium i.e. unconstrained boundary reactions. Any non-zero
growth rate is accepted to pass this test.
"""
ann = test_biomass_open_production.annotation
helpers.open_boundaries(model)
ann["data"][reaction_id] = helpers.run_fba(model, reaction_id)
ann["metric"][reaction_id] = 1.0 # Placeholder value.
ann["message"][reaction_id] = wrapper.fill(
"""Using the biomass reaction {} this is the growth rate that can be
achieved when the model is simulated on a complete medium i.e.
with all the boundary reactions unconstrained: {}
""".format(reaction_id, ann["data"][reaction_id]))
assert ann["data"][reaction_id] > 0.0, ann["message"][reaction_id]
def find_metabolites_produced_with_closed_bounds(model):
"""
Return metabolites that can be produced when boundary reactions are closed.
Parameters
----------
model : cobra.Model
The metabolic model under investigation.
"""
mets_produced = list()
helpers.close_boundaries_sensibly(model)
for met in model.metabolites:
with model:
exch = model.add_boundary(met,
type='irrex',
reaction_id='IRREX',
lb=0,
ub=1)
if helpers.run_fba(model, exch.id) > 0:
mets_produced.append(met)
return mets_produced
def test_fast_growth_default(model, reaction_id):
u"""
Expect the predicted growth rate for each BOF to be below 2.81.
The growth rate of a metabolic model should not be faster than that of the
fastest growing organism. This is based on a doubling time of Vibrio
natriegens which was reported to be 14.8 minutes by: Henry H. Lee, Nili
Ostrov, Brandon G. Wong, Michaela A. Gold, Ahmad S. Khalil,
George M. Church
in https://www.biorxiv.org/content/biorxiv/early/2016/06/12/058487.full.pdf
The calculation ln(2)/(14.8/60) ~ 2.81 yields the corresponding growth
rate.
Implementation:
Calculate the solution of FBA with the biomass reaction set as objective
function and a model's default constraints. Then check if the objective
value is higher than 2.81.
"""
ann = test_fast_growth_default.annotation
outcome = helpers.run_fba(model, reaction_id) > 2.81
ann["data"][reaction_id] = outcome
ann["metric"][reaction_id] = 1.0 - float(outcome)
if ann["data"][reaction_id]:
ann["message"][reaction_id] = wrapper.fill(
"""Using the biomass reaction {} and when the model is simulated on
the provided default medium the growth rate is *higher* than that
of the fastest bacteria.
This could be due to inconsistencies in the network or missing
constraints.""".format(reaction_id))
else:
ann["message"][reaction_id] = wrapper.fill(
"""Using the biomass reaction {} and when the model is simulated on
the provided default medium the growth rate is *lower* than that
of the fastest bacteria. This is to be expected for
a majority of organisms.""".format(reaction_id))
assert outcome, ann["message"][reaction_id]
def test_biomass_default_production(model, reaction_id):
"""
Expect biomass production in default medium.
Using flux balance analysis this test optimizes the model for growth in
the medium that is set by default. Any non-zero growth rate is accepted to
pass this test.
Implementation:
Calculate the solution of FBA with the biomass reaction set as objective
function and the model's default constraints.
"""
ann = test_biomass_default_production.annotation
ann["data"][reaction_id] = helpers.run_fba(model, reaction_id)
outcome = ann["data"][reaction_id] > 1E-07
ann["metric"][reaction_id] = 1.0 - float(outcome)
ann["message"][reaction_id] = wrapper.fill(
"""Using the biomass reaction {} this is the growth rate (1/h) that
can be achieved when the model is simulated on the provided
default medium: {}
""".format(reaction_id, ann["data"][reaction_id]))
assert outcome, ann["message"][reaction_id]
def test_biomass_open_production(model, reaction_id):
"""
Expect biomass production in complete medium.
Using flux balance analysis this test optimizes the model for growth using
a complete medium i.e. unconstrained boundary reactions. Any non-zero
growth rate is accepted to pass this test.
Implementation:
Calculate the solution of FBA with the biomass reaction set as objective
function and after removing any constraints from all boundary reactions.
"""
ann = test_biomass_open_production.annotation
helpers.open_boundaries(model)
ann["data"][reaction_id] = helpers.run_fba(model, reaction_id)
outcome = ann["data"][reaction_id] > 1E-07
ann["metric"][reaction_id] = 1.0 - float(outcome)
ann["message"][reaction_id] = wrapper.fill(
"""Using the biomass reaction {} this is the growth rate that can be
achieved when the model is simulated on a complete medium i.e.
with all the boundary reactions unconstrained: {}
""".format(reaction_id, ann["data"][reaction_id]))
assert outcome, ann["message"][reaction_id]
