Fix dgfs

.github/workflows/run_tox.yml

@@ -12,7 +12,7 @@ on:
   workflow_dispatch: {}
 
 env:
-  CMDSTAN_VERSION: "2.32.2"
+  CMDSTAN_VERSION: "2.33.1"
 
 jobs:
   build:

docs/inputting.md

@@ -454,3 +454,34 @@ kcat = [
   {enzyme = "PROT1", reaction = "PROT", init = 0.264744},
 ]
 ```
+
+## Fixing parameter values
+
+Sometimes it is useful to model a parameter as if its value were known exactly.
+For example, the formation energies of metabolites that are only involved in
+irreversible reactions are typically not identified by Maud's statistical
+model. Fixing these unidentified parameters can improve computational
+performance without loss of any information. Another use might be to test
+whether a particular parameter value is feasible at all.
+
+Maud currently supports fixing the values of `dgf` parameters. This can be done
+for independent parameter inputs by adding a `fixed_value` field to the
+relevant items as shown here:
+
+```toml
+dgf = [
+  {location = -1, metabolite = "M1", scale = 0.05, fixed_value = -1},
+]
+```
+
+If a multivariate input is used for `dgf`, fixed values can be specified using
+a separate table, like this:
+
+```toml
+[dgf]
+ids = ["M1", "M2", "M3"]
+mean_vector = [1, 2, 3]
+covariance_matrix = [[1, 2, 3], [1, 2, 1], [3, 2, 1]]
+[dgf.fixed_values]
+M1 = -1
+```

maud/cli.py

@@ -16,6 +16,7 @@
 
 """Functions that are exposed to the command line interface live here."""
 
+import json
 import os
 import shutil
 from datetime import datetime
@@ -102,6 +103,13 @@ def do_sample(data_path, output_dir):
     stanfit = sample(mi, samples_path)
     print(stanfit.diagnose())
     print(stanfit.summary())
+    if stanfit.metric is not None:
+        for i, chain_metric in enumerate(stanfit.metric):
+            chain_metric_dict = {"inv_metric": chain_metric.tolist()}
+            with open(
+                os.path.join(samples_path, f"metric-{str(i)}.json"), "w"
+            ) as f:
+                json.dump(chain_metric_dict, f)
     idata = get_idata(stanfit.runset.csv_files, mi, "train")
     idata.to_json(os.path.join(output_path, "idata.json"))
     return output_path

maud/data/example_inputs/example_ode/inits.json

@@ -1,118 +1 @@
-{
-  "dgf": [
-    10.0,
-    2.0,
-    5.0,
-    0.0
-  ],
-  "km": [
-    0.5,
-    1.0,
-    2.0,
-    0.5,
-    1.0,
-    2.0,
-    0.5,
-    2.0,
-    1.0,
-    3.0000000000000004
-  ],
-  "kcat": [
-    0.5,
-    2.0,
-    1.0,
-    2.0,
-    1.0
-  ],
-  "kcat_phos": [],
-  "ki": [
-    1.0
-  ],
-  "psi": [
-    0.0
-  ],
-  "dissociation_constant": [
-    0.3,
-    0.9
-  ],
-  "transfer_constant": [
-    1.0,
-    1.0
-  ],
-  "conc_unbalanced_train": [
-    [
-      4.999999999999999,
-      0.5
-    ]
-  ],
-  "drain_train": [
-    []
-  ],
-  "conc_enzyme_train": [
-    [
-      1.0,
-      2.0,
-      3.0000000000000004,
-      2.0,
-      3.0000000000000004
-    ]
-  ],
-  "conc_phos_train": [
-    []
-  ],
-  "log_km_z": [
-    0.0,
-    0.0,
-    0.0,
-    0.0,
-    0.0,
-    0.0,
-    0.0,
-    0.0,
-    0.0,
-    0.0
-  ],
-  "log_kcat_z": [
-    0.0,
-    0.0,
-    0.0,
-    0.0,
-    0.0
-  ],
-  "log_kcat_phos_z": [],
-  "log_ki_z": [
-    0.0
-  ],
-  "psi_z": [
-    0.0
-  ],
-  "log_dissociation_constant_z": [
-    0.0,
-    0.0
-  ],
-  "log_transfer_constant_z": [
-    0.0,
-    0.0
-  ],
-  "log_conc_unbalanced_train_z": [
-    [
-      0.0,
-      0.0
-    ]
-  ],
-  "drain_train_z": [
-    []
-  ],
-  "log_conc_enzyme_train_z": [
-    [
-      0.0,
-      0.0,
-      0.0,
-      0.0,
-      0.0
-    ]
-  ],
-  "log_conc_phos_train_z": [
-    []
-  ]
-}
+{"dgf": [10.0, 2.0, 5.0, 0.0], "dgf_free": [10.0, 2.0, 5.0, 0.0], "km": [0.5, 1.0, 2.0, 0.5, 1.0, 2.0, 0.5, 2.0, 1.0, 3.0000000000000004], "log_km_z": [0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0, 0.0], "ki": [1.0], "log_ki_z": [0.0], "kcat": [0.5, 2.0, 1.0, 2.0, 1.0], "log_kcat_z": [0.0, 0.0, 0.0, 0.0, 0.0], "dissociation_constant": [0.3, 0.9], "log_dissociation_constant_z": [0.0, 0.0], "transfer_constant": [1.0, 1.0], "log_transfer_constant_z": [0.0, 0.0], "kcat_pme": [], "log_kcat_pme_z": [], "drain_train": [[]], "drain_train_z": [[]], "drain_test": [[]], "drain_test_z": [[]], "conc_enzyme_train": [[1.0, 2.0, 3.0000000000000004, 2.0, 3.0000000000000004]], "log_conc_enzyme_train_z": [[0.0, 0.0, 0.0, 0.0, 0.0]], "conc_enzyme_test": [[1.0, 2.0, 3.0000000000000004, 2.0, 3.0000000000000004]], "log_conc_enzyme_test_z": [[0.0, 0.0, 0.0, 0.0, 0.0]], "conc_unbalanced_train": [[4.999999999999999, 0.5]], "log_conc_unbalanced_train_z": [[0.0, 0.0]], "conc_unbalanced_test": [[4.999999999999999, 0.5]], "log_conc_unbalanced_test_z": [[0.0, 0.0]], "conc_pme_train": [[]], "log_conc_pme_train_z": [[]], "conc_pme_test": [[]], "log_conc_pme_test_z": [[]], "psi_train": [0.0], "psi_train_z": [0.0], "psi_test": [0.0], "psi_test_z": [0.0]}

maud/data/example_inputs/example_ode/input_data_train.json

@@ -1 +1 @@
-{"N_mic": 4, "N_edge_sub": 5, "N_edge_prod": 5, "N_edge": 5, "N_unbalanced": 2, "N_enzyme": 5, "N_phosphorylation": 0, "N_pme": 0, "N_competitive_inhibition": 1, "N_allostery": 2, "N_allosteric_enzyme": 2, "N_drain": 0, "N_km": 10, "N_sub_km": 5, "N_prod_km": 5, "S": [[-1, -1, -1, 0, 0], [1, 0, 0, -1, 0], [0, 1, 1, 0, -1], [0, 0, 0, 1, 1]], "N_reaction": 4, "N_metabolite": 4, "balanced_mic_ix": [2, 3], "unbalanced_mic_ix": [1, 4], "ci_mic_ix": [4], "edge_type": [1, 1, 1, 1, 1], "edge_to_enzyme": [1, 2, 3, 4, 5], "edge_to_tc": [0, 1, 2, 0, 0], "edge_to_drain": [0, 0, 0, 0, 0], "edge_to_reaction": [1, 2, 2, 3, 4], "water_stoichiometry": [0.0, 0.0, 0.0, 0.0, 0.0], "transported_charge": [0.0, 0.0, 0.0, 0.0, 0.0], "mic_to_met": [1, 2, 3, 4], "subunits": [1, 1, 1, 1, 1], "sub_by_edge_long": [1, 1, 1, 2, 3], "sub_by_edge_bounds": [[1, 1], [2, 2], [3, 3], [4, 4], [5, 5]], "prod_by_edge_long": [2, 3, 3, 4, 4], "prod_by_edge_bounds": [[1, 1], [2, 2], [3, 3], [4, 4], [5, 5]], "sub_km_ix_by_edge_long": [1, 3, 5, 7, 9], "sub_km_ix_by_edge_bounds": [[1, 1], [2, 2], [3, 3], [4, 4], [5, 5]], "prod_km_ix_by_edge_long": [2, 4, 6, 8, 10], "prod_km_ix_by_edge_bounds": [[1, 1], [2, 2], [3, 3], [4, 4], [5, 5]], "ci_ix_long": [1], "ci_ix_bounds": [[1, 1], [2, 1], [2, 1], [2, 1], [2, 1]], "allostery_ix_long": [1, 2], "allostery_ix_bounds": [[1, 0], [1, 1], [2, 2], [3, 2], [3, 2]], "allostery_type": [1, 2], "allostery_mic": [3, 3], "phosphorylation_ix_long": [], "phosphorylation_ix_bounds": [[1, 0], [1, 0], [1, 0], [1, 0], [1, 0]], "phosphorylation_type": [], "phosphorylation_pme": [], "priors_km": [[-0.6931471805599453, 0.0, 0.6931471805599453, -0.6931471805599453, 0.0, 0.6931471805599453, -0.6931471805599453, 0.6931471805599453, 0.0, 1.0986122886681098], [0.2, 0.2, 0.2, 0.2, 0.2, 0.2, 0.2, 0.2, 0.2, 0.2]], "priors_ki": [[0.0], [0.2]], "priors_kcat": [[-0.6931471805599453, 0.6931471805599453, 0.0, 0.6931471805599453, 0.0], [0.2, 0.2, 0.2, 0.2, 0.2]], "priors_dissociation_constant": [[-1.2039728043259361, -0.10536051565782628], [0.2, 0.2]], "priors_transfer_constant": [[0.0, 0.0], [0.2, 0.2]], "priors_kcat_pme": [[], []], "priors_drain_train": [[[]], [[]]], "priors_conc_enzyme_train": [[[0.0, 0.6931471805599453, 1.0986122886681098, 0.6931471805599453, 1.0986122886681098]], [[0.2, 0.2, 0.2, 0.2, 0.2]]], "priors_conc_unbalanced_train": [[[1.6094379124341003, -0.6931471805599453]], [[0.2, 0.2]]], "priors_conc_pme_train": [[[]], [[]]], "priors_psi_train": [[0.0], [2.0]], "prior_loc_dgf": [10.0, 2.0, 5.0, 0.0], "prior_cov_dgf": [[0.2, 0.0, 0.0, 0.0], [0.0, 0.2, 0.0, 0.0], [0.0, 0.0, 0.2, 0.0], [0.0, 0.0, 0.0, 0.2]], "N_experiment_train": 1, "N_flux_measurement_train": 2, "N_enzyme_measurement_train": 0, "N_conc_measurement_train": 2, "N_enzyme_knockout_train": 0, "N_pme_knockout_train": 0, "temperature_train": [298.15], "enzyme_knockout_train_long": [], "enzyme_knockout_train_bounds": [[1, 0]], "pme_knockout_train_long": [], "pme_knockout_train_bounds": [[1, 0]], "yconc_train": [0.323117, 3.02187], "sigma_yconc_train": [0.1, 0.1], "experiment_yconc_train": [1, 1], "mic_ix_yconc_train": [2, 3], "yflux_train": [0.421816, 2.11674], "sigma_yflux_train": [0.01, 0.01], "experiment_yflux_train": [1, 1], "reaction_yflux_train": [3, 4], "yenz_train": [], "sigma_yenz_train": [], "experiment_yenz_train": [], "enzyme_yenz_train": [], "likelihood": 1, "drain_small_conc_corrector": 1e-06, "reject_non_steady": 1, "penalize_non_steady": 0, "steady_state_threshold_abs": 1e-08, "steady_state_threshold_rel": 0.001, "steady_state_penalty_rel": 1e-08, "rel_tol_ode": 1e-09, "abs_tol_ode": 1e-09, "max_num_steps_ode": 1000000000, "rel_tol_alg": 1e-07, "abs_tol_alg": 1e-07, "max_num_steps_alg": 1000000, "conc_init": [[0.323117, 3.02187]]}
+{"N_mic": 4, "N_edge_sub": 5, "N_edge_prod": 5, "N_edge": 5, "N_unbalanced": 2, "N_enzyme": 5, "N_phosphorylation": 0, "N_pme": 0, "N_competitive_inhibition": 1, "N_allostery": 2, "N_allosteric_enzyme": 2, "N_drain": 0, "N_km": 10, "N_sub_km": 5, "N_prod_km": 5, "S": [[-1, -1, -1, 0, 0], [1, 0, 0, -1, 0], [0, 1, 1, 0, -1], [0, 0, 0, 1, 1]], "N_reaction": 4, "N_metabolite": 4, "balanced_mic_ix": [2, 3], "unbalanced_mic_ix": [1, 4], "ci_mic_ix": [4], "edge_type": [1, 1, 1, 1, 1], "edge_to_enzyme": [1, 2, 3, 4, 5], "edge_to_tc": [0, 1, 2, 0, 0], "edge_to_drain": [0, 0, 0, 0, 0], "edge_to_reaction": [1, 2, 2, 3, 4], "water_stoichiometry": [0.0, 0.0, 0.0, 0.0, 0.0], "transported_charge": [0.0, 0.0, 0.0, 0.0, 0.0], "mic_to_met": [1, 2, 3, 4], "subunits": [1, 1, 1, 1, 1], "sub_by_edge_long": [1, 1, 1, 2, 3], "sub_by_edge_bounds": [[1, 1], [2, 2], [3, 3], [4, 4], [5, 5]], "prod_by_edge_long": [2, 3, 3, 4, 4], "prod_by_edge_bounds": [[1, 1], [2, 2], [3, 3], [4, 4], [5, 5]], "sub_km_ix_by_edge_long": [1, 3, 5, 7, 9], "sub_km_ix_by_edge_bounds": [[1, 1], [2, 2], [3, 3], [4, 4], [5, 5]], "prod_km_ix_by_edge_long": [2, 4, 6, 8, 10], "prod_km_ix_by_edge_bounds": [[1, 1], [2, 2], [3, 3], [4, 4], [5, 5]], "ci_ix_long": [1], "ci_ix_bounds": [[1, 1], [2, 1], [2, 1], [2, 1], [2, 1]], "allostery_ix_long": [1, 2], "allostery_ix_bounds": [[1, 0], [1, 1], [2, 2], [3, 2], [3, 2]], "allostery_type": [1, 2], "allostery_mic": [3, 3], "phosphorylation_ix_long": [], "phosphorylation_ix_bounds": [[1, 0], [1, 0], [1, 0], [1, 0], [1, 0]], "phosphorylation_type": [], "phosphorylation_pme": [], "N_dgf_fixed": 0, "dgf_fixed": [], "ix_dgf_free": [1, 2, 3, 4], "ix_dgf_fixed": [], "priors_km": [[-0.6931471805599453, 0.0, 0.6931471805599453, -0.6931471805599453, 0.0, 0.6931471805599453, -0.6931471805599453, 0.6931471805599453, 0.0, 1.0986122886681098], [0.2, 0.2, 0.2, 0.2, 0.2, 0.2, 0.2, 0.2, 0.2, 0.2]], "priors_ki": [[0.0], [0.2]], "priors_kcat": [[-0.6931471805599453, 0.6931471805599453, 0.0, 0.6931471805599453, 0.0], [0.2, 0.2, 0.2, 0.2, 0.2]], "priors_dissociation_constant": [[-1.2039728043259361, -0.10536051565782628], [0.2, 0.2]], "priors_transfer_constant": [[0.0, 0.0], [0.2, 0.2]], "priors_kcat_pme": [[], []], "priors_drain_train": [[[]], [[]]], "priors_conc_enzyme_train": [[[0.0, 0.6931471805599453, 1.0986122886681098, 0.6931471805599453, 1.0986122886681098]], [[0.2, 0.2, 0.2, 0.2, 0.2]]], "priors_conc_unbalanced_train": [[[1.6094379124341003, -0.6931471805599453]], [[0.2, 0.2]]], "priors_conc_pme_train": [[[]], [[]]], "priors_psi_train": [[0.0], [2.0]], "prior_loc_dgf": [10.0, 2.0, 5.0, 0.0], "prior_cov_dgf": [[0.2, 0.0, 0.0, 0.0], [0.0, 0.2, 0.0, 0.0], [0.0, 0.0, 0.2, 0.0], [0.0, 0.0, 0.0, 0.2]], "N_experiment_train": 1, "N_flux_measurement_train": 2, "N_enzyme_measurement_train": 0, "N_conc_measurement_train": 2, "N_enzyme_knockout_train": 0, "N_pme_knockout_train": 0, "temperature_train": [298.15], "enzyme_knockout_train_long": [], "enzyme_knockout_train_bounds": [[1, 0]], "pme_knockout_train_long": [], "pme_knockout_train_bounds": [[1, 0]], "yconc_train": [0.323117, 3.02187], "sigma_yconc_train": [0.1, 0.1], "experiment_yconc_train": [1, 1], "mic_ix_yconc_train": [2, 3], "yflux_train": [0.421816, 2.11674], "sigma_yflux_train": [0.01, 0.01], "experiment_yflux_train": [1, 1], "reaction_yflux_train": [3, 4], "yenz_train": [], "sigma_yenz_train": [], "experiment_yenz_train": [], "enzyme_yenz_train": [], "likelihood": 1, "drain_small_conc_corrector": 1e-06, "reject_non_steady": 1, "penalize_non_steady": 0, "steady_state_threshold_abs": 1e-08, "steady_state_threshold_rel": 0.001, "steady_state_penalty_rel": 1e-08, "rel_tol_ode": 1e-09, "abs_tol_ode": 1e-09, "max_num_steps_ode": 1000000000, "rel_tol_alg": 1e-07, "abs_tol_alg": 1e-07, "max_num_steps_alg": 1000000, "conc_init": [[0.323117, 3.02187]]}

maud/data/example_inputs/linear/config.toml

@@ -14,11 +14,11 @@ save_warmup = true
 seed = 1234
 
 [ode_solver_config]
-abs_tol = 1e-7
-rel_tol = 1e-7
+abs_tol = 1e-4
+rel_tol = 1e-6
 max_num_steps = 1e6
 
 [algebra_solver_config]
-abs_tol = 1e-5
-rel_tol = 1e-5
+abs_tol = 1e-4
+rel_tol = 1e-6
 max_num_steps = 1e6