Unverified Commit 40c47045 authored by St. Elmo's avatar St. Elmo
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implemented reviews

parent 4ae89cb2
Pipeline #50138 passed with stages
in 9 minutes and 40 seconds
......@@ -99,15 +99,16 @@ reaction_standard_gibbs_free_energies = Dict( # kJ/mol
"FUM" => -3.42,
);
# In general you cannot be certain that all fluxes will be positive for a given flux
# In general we cannot be certain that all fluxes will be positive for a given flux
# solution. This poses problems for systematically enforcing that ΔᵣG ≤ 0 for each reaction,
# because it implicitly assumes that all fluxes are positive, as done in the original
# formulation of MMDF. In COBREXA we instead enforce ΔᵣG ⋅ vᵢ ≤ 0, where vᵢ is the flux of
# reaction i. By default all fluxes are assumed to be positive, but by supplying
# thermodynamically consistent flux solution it is possible to drop this implicit assumption
# and makes it easier to directly incorporate the max min driving force into non-customized
# models. Here, customized model means a model written such that a negative ΔᵣG is associated
# with each positive flux in the model, and only positive fluxes are used by the model.
# formulation of MMDF. In `max_min_driving_force` we instead enforce ΔᵣG ⋅ vᵢ ≤ 0, where vᵢ
# is the flux of reaction i. By default all fluxes are assumed to be positive, but by
# supplying thermodynamically consistent flux solution it is possible to drop this implicit
# assumption and makes it easier to directly incorporate the max min driving force into
# non-customized models. Here, customized model means a model written such that a negative
# ΔᵣG is associated with each positive flux in the model, and only positive fluxes are used
# by the model.
flux_solution = flux_balance_analysis_dict( # find a thermodynamically consistent solution
model,
......@@ -116,11 +117,11 @@ flux_solution = flux_balance_analysis_dict( # find a thermodynamically consisten
)
# Run max min driving force analysis with some reasonable constraints on metabolite
# concentration bounds. Note, protons and water are removed from the concentration
# calculation of the optimization problem, thus we specify their IDs in the model
# explicitly. The reason for this is that the Gibbs free energies of biochemical reactions
# are measured at constant pH, so proton concentration is fixed; likewise, we assume that
# reactions occur in aqueous environments, hence water is excluded too.
# concentration bounds. To remove protons and water from the concentration calculations, we
# explicitly specify their IDs. Note, protons and water need to be removed from the
# concentration calculation of the optimization problem, because the Gibbs free energies of
# biochemical reactions are measured at constant pH, so proton concentration is fixed, and
# reactions occur in aqueous environments, hence water concentration does not change.
sol = max_min_driving_force(
model,
......@@ -147,16 +148,16 @@ sol.mmdf
#md # Transporters can be included in MMDF analysis, however water and proton
#md # transporters must be excluded explicitly in `ignore_reaction_ids`. Due to
#md # the way the method is implemented, the ΔᵣG for these transport reactions
#md # will always be 0. If they are not excluded the MMDF will be 0 (if these
#md # reactions are used in the flux solution).
#md # will always be 0. If not excluded, the MMDF will only have a zero solution (if
#md # these reactions are used in the flux solution).
# NExt, we plot the results to show how the concentrations can be used to ensure that
# Next, we plot the results to show how the concentrations can be used to ensure that
# each reach proceeds "down hill" (ΔᵣG < 0) and that the driving force is as
# large as possible across all the reactions in the model. Compare this to the
# driving forces at standard conditions. Note, we only plot glycolysis for simplicity.
# We additionally scale the fluxes according to their stoichiometry in the
# pathway. From the output, it is clear that that metabolite concentrations
# pathway. From the output, we can clearly see that that metabolite concentrations
# play a large role in ensuring the thermodynamic consistency of in vivo reactions.
rids = ["GLCpts", "PGI", "PFK", "FBA", "TPI", "GAPD", "PGK", "PGM", "ENO", "PYK"] # glycolysis
......
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