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LCSB-BioCore · Nov 27, 2021 · d585420 · d585420
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diff --git a/src/analysis/max_min_driving_force.jl b/src/analysis/max_min_driving_force.jl
@@ -151,7 +151,7 @@ function max_min_driving_force(
 
     # add the relative bounds
     for ((mid1, mid2), val) in concentration_ratios
-        idxs = indexin([mid1, mid2], metabolites(model))
+        idxs = indexin([mid1, mid2], metabolites(model)) # TODO: this is not performant
         any(isnothing.(idxs)) &&
             throw(DomainError((mid1, mid2), "metabolite pair not found in model."))
         @constraint(opt_model, logcs[idxs[1]] == log(val) + logcs[idxs[2]])
@@ -188,7 +188,8 @@ end
         reaction_standard_gibbs_free_energies::Dict{String,Float64},
         optimizer;
         workers =[myid()],
-        relax_driving_force = 0.9,
+        optimal_objective_value = nothing,
+        bounds = z -> (z, Inf),
         flux_solution::Dict{String,Float64} = Dict{String,Float64}(),
         proton_ids::Vector{String} = ["h_c", "h_e"],
         water_ids::Vector{String} = ["h2o_c", "h2o_e"],
@@ -206,16 +207,20 @@ end
         ignore_reaction_ids = [],
     )
 
-Perform a variant of flux variability analysis on a max min driving force type problem. All
-the arguments are forwarded to [`max_min_driving_force`](@ref). Calls [`screen`](@ref)
-internally and possibly distributes computation across `workers`. First performs regular max
-min driving force analysis to find the max min driving force of the model. Then iteratively
-maximizes and minimizes the driving force across each reaction, and then the concentrations
-while staying close to the original max min driving force. Specifically, the max min driving
-force is constrained to be beween the optimum, as found using
-[`max_min_driving_force`](@ref), and `relax_driving_force` times the optimum. If
-`relax_driving_force = 1`, then the max min driving force of the problem is fixed to that
-value instead of constrained.
+Perform a variant of flux variability analysis on a max min driving force type problem.
+Arguments are forwarded to [`max_min_driving_force`](@ref). Calls [`screen`](@ref)
+internally and possibly distributes computation across `workers`. If
+`optimal_objective_value = nothing`, the function first performs regular max min driving
+force analysis to find the max min driving force of the model and sets this to
+`optimal_objective_value`. Then iteratively maximizes and minimizes the driving force across
+each reaction, and then the concentrations while staying close to the original max min
+driving force as specified in `bounds`.
+
+The `bounds` is a user-supplied function that specifies the max min driving force bounds for
+the variability optimizations, by default it restricts the flux objective value to the
+precise optimum reached in the normal max min driving force analysis. It can return `-Inf`
+and `Inf` in first and second pair to remove the limit. Use [`gamma_bounds`](@ref) and
+[`objective_bounds`](@ref) for simple bounds.
 
 Returns a matrix of solutions to [`max_min_driving_force`](@ref) additionally constrained as
 described above, where the rows are in the order of the reactions and then the metabolites
@@ -229,50 +234,31 @@ function max_min_driving_force_variability(
     reaction_standard_gibbs_free_energies::Dict{String,Float64},
     optimizer;
     workers = [myid()],
-    relax_driving_force = 0.9,
-    flux_solution::Dict{String,Float64} = Dict{String,Float64}(),
-    proton_ids::Vector{String} = ["h_c", "h_e"],
-    water_ids::Vector{String} = ["h2o_c", "h2o_e"],
-    constant_concentrations::Dict{String,Float64} = Dict{String,Float64}(),
-    concentration_ratios::Dict{Tuple{String,String},Float64} = Dict{
-        Tuple{String,String},
-        Float64,
-    }(),
-    concentration_lb = 1e-9,
-    concentration_ub = 100e-3,
-    T = _constants.T,
-    R = _constants.R,
-    small_flux_tol = 1e-6,
-    modifications = [],
-    ignore_reaction_ids = [],
+    optimal_objective_value = nothing,
+    bounds = z -> (z, Inf),
+    kwargs...
 )
-    initsol = max_min_driving_force(
-        model,
-        reaction_standard_gibbs_free_energies,
-        optimizer;
-        flux_solution,
-        proton_ids,
-        water_ids,
-        constant_concentrations,
-        concentration_ratios,
-        concentration_lb,
-        concentration_ub,
-        T,
-        R,
-        small_flux_tol,
-        modifications,
-        ignore_reaction_ids,
-    )
+    if isnothing(optimal_objective_value)
+            initsol = max_min_driving_force(
+            model,
+            reaction_standard_gibbs_free_energies,
+            optimizer;
+            kwargs...
+        )
+        mmdf = initsol.mmdf
+    else
+        mmdf = optimal_objective_value
+    end
 
-    mmdf = initsol.mmdf
+    lb, ub = bounds(mmdf)
 
     dgr_variants = [
-        [[_mmdf_add_df_bound(mmdf, relax_driving_force), _mmdf_dgr_objective(ridx, sense)]] for ridx = 1:n_reactions(model), sense in [MOI.MAX_SENSE, MOI.MIN_SENSE]
+        [[_mmdf_add_df_bound(lb, ub), _mmdf_dgr_objective(ridx, sense)]] for ridx = 1:n_reactions(model), sense in [MOI.MAX_SENSE, MOI.MIN_SENSE]
     ]
     concen_variants = [
         [
             [
-                _mmdf_add_df_bound(mmdf, relax_driving_force),
+                _mmdf_add_df_bound(lb, ub),
                 _mmdf_concen_objective(midx, sense),
             ],
         ] for midx = 1:n_metabolites(model), sense in [MOI.MAX_SENSE, MOI.MIN_SENSE]
@@ -285,18 +271,7 @@ function max_min_driving_force_variability(
             m,
             reaction_standard_gibbs_free_energies,
             optimizer;
-            flux_solution,
-            proton_ids,
-            water_ids,
-            constant_concentrations,
-            concentration_ratios,
-            concentration_lb,
-            concentration_ub,
-            T,
-            R,
-            small_flux_tol,
-            modifications = [modifications; args],
-            ignore_reaction_ids,
+            kwargs...
         ),
         workers,
     )
@@ -323,12 +298,12 @@ end
 """
 Helper function to add a new constraint on the driving force.
 """
-function _mmdf_add_df_bound(dg_opt, gamma)
+function _mmdf_add_df_bound(lb, ub)
     (model, opt_model) -> begin
-        if gamma == 1
-            fix(opt_model[:mmdf], dg_opt; force = true)
+        if lb == ub
+            fix(opt_model[:mmdf], lb; force = true)
         else
-            @constraint(opt_model, gamma * dg_opt <= opt_model[:mmdf])
+            @constraint(opt_model, lb <= opt_model[:mmdf] <= ub)
         end
     end
 end
diff --git a/test/analysis/max_min_driving_force.jl b/test/analysis/max_min_driving_force.jl
@@ -8,8 +8,6 @@
         modifications = [add_loopless_constraints()],
     )
 
-    reaction_standard_gibbs_free_energies = get_thermo_data()
-
     sol = max_min_driving_force(
         model,
         reaction_standard_gibbs_free_energies,
@@ -34,6 +32,7 @@
         model,
         reaction_standard_gibbs_free_energies,
         Tulip.Optimizer;
+        bounds = gamma_bounds(0.9),
         flux_solution = flux_solution,
         proton_ids = ["h_c", "h_e"],
         water_ids = ["h2o_c", "h2o_e"],

diff --git a/test/data_static.jl b/test/data_static.jl
@@ -73,82 +73,78 @@ test_toyModel() = CoreModel(
     ["m1[c]", "m3[c]", "m2[c]", "m1[e]", "m3[e]", "biomass[c]"],
 )
 
-function get_thermo_data()
-    # these data come from eQuilibrator. Use the Julia API to get them.
-    reaction_standard_gibbs_free_energies = Dict(
-        "ACALD" => -21.268198981756314,
-        "PTAr" => 8.651025243027988,
-        "ALCD2x" => 17.47260052762408,
-        "PDH" => -34.246780702043225,
-        "PYK" => -24.48733600711958,
-        "CO2t" => 0.0,
-        "MALt2_2" => -6.839209921974724,
-        "CS" => -39.330940148207475,
-        "PGM" => -4.470553692565886,
-        "TKT1" => -1.4976299544215408,
-        "ACONTa" => 8.46962176350985,
-        "GLNS" => -15.771242654033706,
-        "ICL" => 9.53738025507404,
-        "FBA" => 23.376920310319235,
-        "SUCCt3" => -43.97082007726285,
-        "FORt2" => -3.4211767267069124,
-        "G6PDH2r" => -7.3971867270165035,
-        "AKGDH" => -28.235442362320782,
-        "TKT2" => -10.318436817276165,
-        "FRD7" => 73.61589524884772,
-        "SUCOAS" => -1.1586968559555615,
-        "FBP" => -11.606887851480572,
-        "ICDHyr" => 5.398885342794983,
-        "AKGt2r" => 10.085299238039797,
-        "GLUSy" => -47.21690395283849,
-        "TPI" => 5.621932460512994,
-        "FORt" => 13.509690780237293,
-        "ACONTb" => -1.622946931741609,
-        "GLNabc" => -30.194559792842753,
-        "RPE" => -3.3881719029747615,
-        "ACKr" => 14.027197131450492,
-        "THD2" => -33.84686533309243,
-        "PFL" => -19.814421615735,
-        "RPI" => 4.477649590945703,
-        "D_LACt2" => -3.4223903975852004,
-        "TALA" => -0.949571985515206,
-        "PPCK" => 10.659841402564751,
-        "ACt2r" => -3.4196348363397995,
-        "NH4t" => -13.606633927039097,
-        "PGL" => -25.94931748161696,
-        "NADTRHD" => -0.014869680795754903,
-        "PGK" => 19.57192102020454,
-        "LDH_D" => 20.04059765689044,
-        "ME1" => 12.084968268076864,
-        "PIt2r" => 10.415108493818785,
-        "ATPS4r" => -37.570267233299816,
-        "PYRt2" => -3.422891289768689,
-        "GLCpts" => -45.42430981510088,
-        "GLUDy" => 32.834943812395665,
-        "CYTBD" => -59.700410815493775,
-        "FUMt2_2" => -6.845105500839001,
-        "FRUpts2" => -42.67529760694199,
-        "GAPD" => 0.5307809794271634,
-        "H2Ot" => -1.5987211554602254e-14,
-        "PPC" => -40.81304419704113,
-        "NADH16" => -80.37770501380615,
-        "PFK" => -18.546314942995934,
-        "MDH" => 25.912462872631522,
-        "PGI" => 2.6307087407442395,
-        "O2t" => 0.0,
-        "ME2" => 12.099837948872533,
-        "GND" => 10.312275879236381,
-        "SUCCt2_2" => -6.82178244356977,
-        "GLUN" => -14.381960140443113,
-        "ETOHt2r" => -16.930867506944217,
-        "ADK1" => 0.3893321583896068,
-        "ACALDt" => -3.197442310920451e-14,
-        "SUCDi" => -73.61589524884772,
-        "ENO" => -3.8108376097261782,
-        "MALS" => -39.22150045995042,
-        "GLUt2r" => -3.499043558772904,
-        "PPS" => -6.0551989457468665,
-        "FUM" => -3.424133018702122,
-    )
-    return reaction_standard_gibbs_free_energies
-end
+const reaction_standard_gibbs_free_energies = Dict(
+    "ACALD" => -21.268198981756314,
+    "PTAr" => 8.651025243027988,
+    "ALCD2x" => 17.47260052762408,
+    "PDH" => -34.246780702043225,
+    "PYK" => -24.48733600711958,
+    "CO2t" => 0.0,
+    "MALt2_2" => -6.839209921974724,
+    "CS" => -39.330940148207475,
+    "PGM" => -4.470553692565886,
+    "TKT1" => -1.4976299544215408,
+    "ACONTa" => 8.46962176350985,
+    "GLNS" => -15.771242654033706,
+    "ICL" => 9.53738025507404,
+    "FBA" => 23.376920310319235,
+    "SUCCt3" => -43.97082007726285,
+    "FORt2" => -3.4211767267069124,
+    "G6PDH2r" => -7.3971867270165035,
+    "AKGDH" => -28.235442362320782,
+    "TKT2" => -10.318436817276165,
+    "FRD7" => 73.61589524884772,
+    "SUCOAS" => -1.1586968559555615,
+    "FBP" => -11.606887851480572,
+    "ICDHyr" => 5.398885342794983,
+    "AKGt2r" => 10.085299238039797,
+    "GLUSy" => -47.21690395283849,
+    "TPI" => 5.621932460512994,
+    "FORt" => 13.509690780237293,
+    "ACONTb" => -1.622946931741609,
+    "GLNabc" => -30.194559792842753,
+    "RPE" => -3.3881719029747615,
+    "ACKr" => 14.027197131450492,
+    "THD2" => -33.84686533309243,
+    "PFL" => -19.814421615735,
+    "RPI" => 4.477649590945703,
+    "D_LACt2" => -3.4223903975852004,
+    "TALA" => -0.949571985515206,
+    "PPCK" => 10.659841402564751,
+    "ACt2r" => -3.4196348363397995,
+    "NH4t" => -13.606633927039097,
+    "PGL" => -25.94931748161696,
+    "NADTRHD" => -0.014869680795754903,
+    "PGK" => 19.57192102020454,
+    "LDH_D" => 20.04059765689044,
+    "ME1" => 12.084968268076864,
+    "PIt2r" => 10.415108493818785,
+    "ATPS4r" => -37.570267233299816,
+    "PYRt2" => -3.422891289768689,
+    "GLCpts" => -45.42430981510088,
+    "GLUDy" => 32.834943812395665,
+    "CYTBD" => -59.700410815493775,
+    "FUMt2_2" => -6.845105500839001,
+    "FRUpts2" => -42.67529760694199,
+    "GAPD" => 0.5307809794271634,
+    "H2Ot" => -1.5987211554602254e-14,
+    "PPC" => -40.81304419704113,
+    "NADH16" => -80.37770501380615,
+    "PFK" => -18.546314942995934,
+    "MDH" => 25.912462872631522,
+    "PGI" => 2.6307087407442395,
+    "O2t" => 0.0,
+    "ME2" => 12.099837948872533,
+    "GND" => 10.312275879236381,
+    "SUCCt2_2" => -6.82178244356977,
+    "GLUN" => -14.381960140443113,
+    "ETOHt2r" => -16.930867506944217,
+    "ADK1" => 0.3893321583896068,
+    "ACALDt" => -3.197442310920451e-14,
+    "SUCDi" => -73.61589524884772,
+    "ENO" => -3.8108376097261782,
+    "MALS" => -39.22150045995042,
+    "GLUt2r" => -3.499043558772904,
+    "PPS" => -6.0551989457468665,
+    "FUM" => -3.424133018702122,
+)