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Merged
Robotato merged 8 commits into from
Apr 13, 2026
Merged

Small changes to metabolism_redux_classic #398

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9024465
Add bad reactions, move objective weights to parameters, normalize ho…
Robotato Apr 1, 2026
1b533c0
Fix fallback behavior for missing objective weights
Robotato Apr 1, 2026
a72fb2d
Update test to use new call signature
Robotato Apr 3, 2026
9cae197
Remove kinetic bounds listener, since it cannot be Parquet-serialized
Robotato Apr 7, 2026
f6cd5d5
update config and test full sim with metabolism_redux_classic
Robotato Apr 9, 2026
600fffb
Merge branch 'master' into metabolism-redux-classic-bump
Robotato Apr 9, 2026
08fbc4e
Merge branch 'master' into metabolism-redux-classic-bump
Robotato Apr 13, 2026
6654704
Merge branch 'master' into metabolism-redux-classic-bump
Robotato Apr 13, 2026
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8 changes: 8 additions & 0 deletions configs/metabolism_redux_classic.json
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Original file line number Diff line number Diff line change
@@ -1,6 +1,14 @@
{
"experiment_id" : "metabolism_redux",
"max_duration" : 10,
"fail_at_max_duration": false,
"progress_bar": true,
"n_init_sims": 1,
"emitter": "parquet",
"emitter_arg": {"out_dir": "out/"},
"fixed_media": "minimal",
"condition": "basal",

"swap_processes" : {
"ecoli-metabolism" : "ecoli-metabolism-redux-classic"
},
Expand Down
124 changes: 102 additions & 22 deletions ecoli/processes/metabolism_redux_classic.py
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Original file line number Diff line number Diff line change
Expand Up @@ -5,6 +5,7 @@
import numpy as np
import numpy.typing as npt
import time
import pytest
from unum import Unum
import warnings
from scipy.sparse import csr_matrix
Expand Down Expand Up @@ -47,7 +48,7 @@
"R15-RXN-MET/CPD-479//CPD-479/MET.25.",
"TRANS-RXN-218",
"TRANS-RXN0-601-PROTON//PROTON.15. (reverse)",
"DISULFOXRED-RXN[CCO-PERI-BAC]-MONOMER0-4152/MONOMER0-4438//MONOMER0-4438/MONOMER0-4152.71."
"DISULFOXRED-RXN[CCO-PERI-BAC]-MONOMER0-4152/MONOMER0-4438//MONOMER0-4438/MONOMER0-4152.71." # Commented on Heena's branch?
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@thalassemia thalassemia Apr 10, 2026

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Have you figured out the commented discrepancy?

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@heenasaqib heenasaqib Apr 10, 2026

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Yah, this reaction no longer exists in metabolic_reactions.tsv. I commented it out, instead of deleting it, just in case it serves some deeper purpose in the model that I'm not realizing now.

"DEPHOSICITDEHASE-RXN",
"PHOSICITDEHASE-RXN",
"GLYCOLALD-DEHYDROG-RXN",
Expand All @@ -63,6 +64,12 @@
"RXN-22461",
"RXN-22462",
"RXN-22463",
"PYRROLINECARBDEHYDROG-RXN",
"RXN0-7008-PRO/UBIQUINONE-8//L-DELTA1-PYRROLINE_5-CARBOXYLATE/CPD-9956/PROTON.67.",
"GLUCOKIN-RXN-GLC/ATP//ALPHA-GLC-6-P/ADP/PROTON.34.", # gets confused with PTS
"PRPPSYN-RXN-CPD-15318/ATP//PRPP/AMP/PROTON.31.", # duplicate
"TRANS-RXN0-574-GLC//GLC.9.", # duplicate
"GLUCOKIN-RXN-GLC/ATP//D-glucopyranose-6-phosphate/ADP/PROTON.48.", # duplicate
]

# not key central carbon met
Expand Down Expand Up @@ -134,6 +141,12 @@ class MetabolismReduxClassic(Step):
"cell_density": 1100 * units.g / units.L,
"concentration_updates": None,
"maintenance_reaction": {},
"objective_weights": {
"secretion": 0.01,
"efficiency": 0.000001,
"kinetics": 0.0000001,
"homeostatic": 1,
},
}

def __init__(self, parameters):
Expand Down Expand Up @@ -293,7 +306,6 @@ def ports_schema(self):
"estimated_exchange_dmdt": {},
"estimated_intermediate_dmdt": [],
"target_kinetic_fluxes": [],
"target_kinetic_bounds": [],
"reaction_catalyst_counts": [],
"maintenance_target": 0,
}
Expand Down Expand Up @@ -454,14 +466,11 @@ def next_update(self, timestep, states):
target_kinetic_values = enzyme_kinetic_boundaries[:, 1]
target_kinetic_bounds = enzyme_kinetic_boundaries[:, [0, 2]]

# TODO (Cyrus) solve network flow problem to get fluxes
objective_weights = {
"secretion": 0.01,
"efficiency": 0.000001,
"kinetics": 0.0000001,
}
objective_weights = self.parameters["objective_weights"]

solution: FlowResult = self.network_flow_model.solve(
homeostatic_targets=target_homeostatic_dmdt,
homeostatic_concs=homeostatic_metabolite_concentrations,
homeostatic_dm_targets=target_homeostatic_dmdt,
maintenance_target=maintenance_target,
kinetic_targets=target_kinetic_values,
binary_kinetic_idx=binary_kinetic_idx,
Expand Down Expand Up @@ -507,7 +516,6 @@ def next_update(self, timestep, states):
"estimated_homeostatic_dmdt": estimated_homeostatic_dmdt,
"target_homeostatic_dmdt": target_homeostatic_dmdt,
"target_kinetic_fluxes": target_kinetic_flux,
"target_kinetic_bounds": target_kinetic_bounds,
"estimated_exchange_dmdt": estimated_exchange_dmdt,
"estimated_intermediate_dmdt": estimated_intermediate_dmdt,
"maintenance_target": target_maintenance_flux,
Expand Down Expand Up @@ -634,7 +642,8 @@ def set_up_exchanges(self, exchanges: set[str], uptakes: set[str]):

def solve(
self,
homeostatic_targets: Optional[Iterable[float]] = None,
homeostatic_concs: Iterable[float],
homeostatic_dm_targets: Iterable[float],
maintenance_target: float = 0,
kinetic_targets: Optional[Iterable[float]] = None,
binary_kinetic_idx: Optional[Iterable[int]] = None,
Expand All @@ -658,29 +667,36 @@ def solve(
if self.maintenance_idx is not None:
constr.append(v[self.maintenance_idx] == maintenance_target)
# If enzymes not present, constrain rxn flux to 0
if binary_kinetic_idx:
if binary_kinetic_idx is not None:
constr.append(v[binary_kinetic_idx] == 0)

constr.extend([v >= 0, v <= upper_flux_bound, e >= 0, e <= upper_flux_bound])

loss = 0
loss += cp.norm1(dm[self.homeostatic_idx] - homeostatic_targets)
# Must normalize by metabolite concentrations to prevent negative counts.
homeostatic_term = cp.norm1(
(dm[self.homeostatic_idx] - homeostatic_dm_targets) / homeostatic_concs
)
loss += (
objective_weights["homeostatic"] * homeostatic_term
if "homeostatic" in objective_weights
else 0
)
loss += (
objective_weights["secretion"] * (cp.sum(e[self.secretion_idx]))
if "secretion" in objective_weights
else loss
else 0
)
loss += (
objective_weights["efficiency"] * (cp.sum(v))
if "efficiency" in objective_weights
else loss
else 0
)
loss = (
loss
+ objective_weights["kinetics"]
loss += (
objective_weights["kinetics"]
* cp.norm1(v[self.kinetic_rxn_idx] - kinetic_targets)
if "kinetics" in objective_weights
else loss
else 0
)

p = cp.Problem(cp.Minimize(loss), constr)
Expand Down Expand Up @@ -726,8 +742,9 @@ def test_network_flow_model():
model.set_up_exchanges(exchanges=exchanges, uptakes=uptakes)

solution: FlowResult = model.solve(
homeostatic_targets=list(homeostatic_metabolites.values()),
objective_weights={"secretion": 0.01, "efficiency": 0.0001},
homeostatic_concs=[0.1],
homeostatic_dm_targets=list(homeostatic_metabolites.values()),
objective_weights={"homeostatic": 1, "secretion": 0.01, "efficiency": 0.0001},
upper_flux_bound=100,
solver=cp.GLOP,
)
Expand All @@ -737,7 +754,70 @@ def test_network_flow_model():
)


# TODO (Cyrus) Add test for entire process
@pytest.fixture
def temp_config_dir(tmp_path):
"""Create a temporary directory for test configs."""
return tmp_path


def test_redux_classic(temp_config_dir):
import json
from ecoli.experiments.ecoli_master_sim import EcoliSim

config = {
"experiment_id": "metabolism_redux",
"fail_at_max_duration": False,
"max_duration": 10,
"progress_bar": True,
"emitter": "timeseries",
"fixed_media": "minimal",
"condition": "basal",
"swap_processes": {"ecoli-metabolism": "ecoli-metabolism-redux-classic"},
"exclude_processes": ["exchange_data"],
"flow": {
"ecoli-metabolism-redux-classic": [["ecoli-chromosome-structure"]],
"ecoli-mass-listener": [["ecoli-metabolism-redux-classic"]],
"RNA_counts_listener": [["ecoli-metabolism-redux-classic"]],
"rna_synth_prob_listener": [["ecoli-metabolism-redux-classic"]],
"monomer_counts_listener": [["ecoli-metabolism-redux-classic"]],
"dna_supercoiling_listener": [["ecoli-metabolism-redux-classic"]],
"replication_data_listener": [["ecoli-metabolism-redux-classic"]],
"rnap_data_listener": [["ecoli-metabolism-redux-classic"]],
"unique_molecule_counts": [["ecoli-metabolism-redux-classic"]],
"ribosome_data_listener": [["ecoli-metabolism-redux-classic"]],
},
"raw_output": False,
"operons": True,
"trna_charging": False,
"ppgpp_regulation": False,
"initial_state_gaussian": True,
"trna_attenuation": False,
"variable_elongation_transcription": True,
"variable_elongation_translation": False,
"mechanistic_translation_supply": False,
"mechanistic_aa_transport": False,
"translation_supply": False,
"aa_supply_in_charging": False,
"adjust_timestep_for_charging": False,
"disable_ppgpp_elongation_inhibition": True,
}

config_path = temp_config_dir / "test_metabolism_redux_classic.json"
with open(config_path, "w") as f:
json.dump(config, f)

sim = EcoliSim.from_file(config_path)
sim.build_ecoli()
sim.run()

data = sim.query()
assert data is not None


if __name__ == "__main__":
from tempfile import TemporaryDirectory
from pathlib import Path

test_network_flow_model()
with TemporaryDirectory() as tmp_path:
test_redux_classic(Path(tmp_path))
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