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Merged
edkerk merged 1 commit into from
Nov 3, 2026
Merged

getEnzymeUsage: demand ratio of the usage over the measured concentrations #29

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31 changes: 31 additions & 0 deletions src/enzyme_usage/getEnzymeUsage.m
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Original file line number Diff line number Diff line change
Expand Up @@ -43,6 +43,25 @@
% usage_prot_<id> reaction in the model is left out, with the warning
% getEnzymeUsage:missingUsageReaction.
% - fluxes : vector of fluxes, copy of input fluxes.
% - measuredProtein : sum of the measured concentrations in model.ec.concs
% (mg/gDCW), over the enzymes with a non-NaN entry.
% - demandedProtein : sum of absUsage over the same enzymes (mg/gDCW).
% - demandRatio : demandedProtein / measuredProtein. NaN when no
% concentration is measured; Inf when the measured concentrations sum to 0
% and the demand is positive. A ratio above 1 means that the solution uses
% more of the measured enzymes than was measured, which happens when the
% upper bounds of the usage reactions are above the measurements (for
% instance after flexibilizeEnzConcs). A ratio at or below 1 does not
% exclude that one enzyme exceeds its measurement, since the sum is over
% all measured enzymes; capUsage gives the ratio per enzyme. Enzymes
% without a measured concentration draw from the protein pool and are not
% counted.
% - measuredProteinActive, demandRatioActive : the same two values restricted
% to the enzymes with an absUsage above 1e-7 mg/gDCW. Measured enzymes
% that are inactive in the solution raise measuredProtein and can hide a
% conflict among the active ones.
% The five fields are computed over all enzymes with a usage reaction,
% whatever the value of zero.
%
% Examples
% --------
Expand All @@ -61,13 +80,17 @@
error('This function does not work on GECKO light models.')
end
usageData.protID = ecModel.ec.enzymes;
concs = nan(numel(ecModel.ec.enzymes),1);
nConcs = min(numel(ecModel.ec.concs),numel(concs));
concs(1:nConcs) = ecModel.ec.concs(1:nConcs);
[~,rxnIdx] = ismember(strcat('usage_prot_',ecModel.ec.enzymes),ecModel.rxns);
noUsageRxn = rxnIdx == 0;
if any(noUsageRxn)
warning('getEnzymeUsage:missingUsageReaction', ...
'The model has no usage reaction for the enzymes %s; they are left out.', ...
strjoin(usageData.protID(noUsageRxn), ', '))
usageData.protID = usageData.protID(~noUsageRxn);
concs = concs(~noUsageRxn);
rxnIdx = rxnIdx(~noUsageRxn);
end

Expand All @@ -76,6 +99,14 @@
usageData.capUsage = abs(usageData.absUsage./usageData.UB);
usageData.fluxes = fluxes;

measured = ~isnan(concs);
active = usageData.absUsage > 1e-7;
usageData.measuredProtein = sum(concs(measured));
usageData.measuredProteinActive = sum(concs(measured & active));
usageData.demandedProtein = sum(usageData.absUsage(measured));
usageData.demandRatio = usageData.demandedProtein / usageData.measuredProtein;
usageData.demandRatioActive = sum(usageData.absUsage(measured & active)) / usageData.measuredProteinActive;

if ~zero
nonzero = usageData.absUsage>0;
usageData.absUsage = usageData.absUsage(nonzero);
Expand Down
14 changes: 14 additions & 0 deletions src/enzyme_usage/reportEnzymeUsage.m
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Expand Up @@ -31,6 +31,14 @@
% the topAbsUsage enzymes with the highest absolute usage.
% totalUsageFlux : double
% total protein pool used, i.e. the upper bound of prot_pool_exchange.
% demandRatio : double
% demandRatio of usageData: the protein used of the enzymes with a
% measured concentration divided by their measured concentrations.
% Above 1, the solution needs more of those enzymes than was
% measured. NaN when usageData has no demandRatio field.
% demandRatioActive : double
% demandRatioActive of usageData: the same ratio over the enzymes
% that carry flux in the solution.
%
% Examples
% --------
Expand Down Expand Up @@ -197,4 +205,10 @@
end
usageReport.topAbsUsage = struct2table(topUsage);
usageReport.totalUsageFlux = protPool;
usageReport.demandRatio = NaN;
usageReport.demandRatioActive = NaN;
if isfield(usageData, 'demandRatio')
usageReport.demandRatio = usageData.demandRatio;
usageReport.demandRatioActive = usageData.demandRatioActive;
end
end
4 changes: 2 additions & 2 deletions test/VerificationMatrix.tsv
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Expand Up @@ -11,8 +11,8 @@ change_model/setProtPoolSize.m tc0005
change_model/getKcatAcrossIsoenzymes.m tc0011, tc0252
change_model/getSubsetEcModel.m tc0258, tc0259
change_model/applyCustomKcats.m tc0227, tc0228, tc0229, tc0230
enzyme_usage/getEnzymeUsage.m tc0507, tc0508
enzyme_usage/reportEnzymeUsage.m tc0508, tc0509
enzyme_usage/getEnzymeUsage.m tc0286, tc0507, tc0508
enzyme_usage/reportEnzymeUsage.m tc0286, tc0508, tc0509
gather_kcats/fuzzyKcatMatching.m tc0010, tc0223, tc0224, tc0225, tc0226, tc0231, tc0239
gather_kcats/getStandardKcat.m tc0256, tc0257, tc0309, tc0310
gather_kcats/mergeDlkcatAndFuzzyKcats.m tc0011; tc0241
Expand Down
80 changes: 80 additions & 0 deletions test/unit_tests/geckoCoreFunctionTests.m
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Expand Up @@ -1291,6 +1291,86 @@ function testPfbaEnzymesFractionOfNegativeOptimum_tc0285(testCase)
verifyGreaterThanOrEqual(testCase, solution.objectiveValue, -11)
end

function testGetEnzymeUsageDemandRatio_tc0286(testCase)
% Verifies the demand ratio of getEnzymeUsage: the usage of the enzymes
% with a measured concentration divided by their measured
% concentrations, over all of them and over those that carry flux, NaN
% without a measured concentration, and the same whatever 'zero' is.
geckoPath = findGECKOroot;
adapter = ModelAdapterManager.getAdapter(fullfile(geckoPath,'test','unit_tests','ecTestGEM', 'TestGEMAdapter.m'));
model = getGeckoTestModel();
ecModel = makeEcModel(model, false, adapter);
ecModel = getECfromGEM(ecModel);
ecModel.ec.kcat(:) = 100;
ecModel.ec.source(:) = {'manual'};
ecModel = applyKcatConstraints(ecModel);
ecModel = setProtPoolSize(ecModel, [], [], [], adapter);

[~, idx] = ismember(strcat('usage_prot_', ecModel.ec.enzymes), ecModel.rxns);
ecModel.ec.concs = nan(numel(ecModel.ec.enzymes), 1);
ecModel.ec.concs(1:3) = [2; 4; 1];
fluxes = zeros(numel(ecModel.rxns), 1);
fluxes(idx(1)) = 3;
fluxes(idx(3)) = 1.5;
fluxes(idx(4)) = 7;

usageData = getEnzymeUsage(ecModel, fluxes);
verifyEqual(testCase, usageData.measuredProtein, 7, 'AbsTol', 1e-12)
verifyEqual(testCase, usageData.demandedProtein, 4.5, 'AbsTol', 1e-12)
verifyEqual(testCase, usageData.demandRatio, 4.5/7, 'AbsTol', 1e-12)
verifyEqual(testCase, usageData.measuredProteinActive, 3, 'AbsTol', 1e-12)
verifyEqual(testCase, usageData.demandRatioActive, 1.5, 'AbsTol', 1e-12)

withoutZero = getEnzymeUsage(ecModel, fluxes, 'zero', false);
verifyEqual(testCase, withoutZero.demandRatio, usageData.demandRatio, 'AbsTol', 1e-12)
verifyEqual(testCase, withoutZero.demandRatioActive, usageData.demandRatioActive, 'AbsTol', 1e-12)

report = reportEnzymeUsage(ecModel, usageData);
verifyEqual(testCase, report.demandRatio, usageData.demandRatio, 'AbsTol', 1e-12)
verifyEqual(testCase, report.demandRatioActive, usageData.demandRatioActive, 'AbsTol', 1e-12)

% A usage below the threshold counts as demand but not as active.
lowFluxes = fluxes;
lowFluxes(idx(2)) = 1e-8;
usageData = getEnzymeUsage(ecModel, lowFluxes);
verifyEqual(testCase, usageData.demandedProtein, 4.5 + 1e-8, 'AbsTol', 1e-12)
verifyEqual(testCase, usageData.measuredProteinActive, 3, 'AbsTol', 1e-12)
verifyEqual(testCase, usageData.demandRatioActive, 1.5, 'AbsTol', 1e-12)

% An enzyme without a usage reaction is left out with its concentration.
reduced = removeReactions(ecModel, ecModel.rxns(idx(1)));
reducedFluxes = fluxes;
reducedFluxes(idx(1)) = [];
warning('off', 'getEnzymeUsage:missingUsageReaction')
restore = onCleanup(@() warning('on', 'getEnzymeUsage:missingUsageReaction'));
usageData = getEnzymeUsage(reduced, reducedFluxes);
verifyEqual(testCase, usageData.measuredProtein, 5, 'AbsTol', 1e-12)
verifyEqual(testCase, usageData.demandedProtein, 1.5, 'AbsTol', 1e-12)
verifyEqual(testCase, usageData.demandRatioActive, 1.5, 'AbsTol', 1e-12)

% A usageData without the demand fields gives NaN in the report.
bare = rmfield(getEnzymeUsage(ecModel, fluxes), ...
{'measuredProtein','measuredProteinActive','demandedProtein','demandRatio','demandRatioActive'});
report = reportEnzymeUsage(ecModel, bare);
verifyTrue(testCase, isnan(report.demandRatio))
verifyTrue(testCase, isnan(report.demandRatioActive))

% A concentration vector shorter than the enzyme list counts as unmeasured.
short = ecModel;
short.ec.concs = [2; 4];
usageData = getEnzymeUsage(short, fluxes);
verifyEqual(testCase, usageData.measuredProtein, 6, 'AbsTol', 1e-12)
short.ec.concs = [];
usageData = getEnzymeUsage(short, fluxes);
verifyTrue(testCase, isnan(usageData.demandRatio))

ecModel.ec.concs(:) = NaN;
usageData = getEnzymeUsage(ecModel, fluxes);
verifyEqual(testCase, usageData.measuredProtein, 0)
verifyTrue(testCase, isnan(usageData.demandRatio))
verifyTrue(testCase, isnan(usageData.demandRatioActive))
end


function ecModel = fixtureForRelaxProteomicsGreedy()
% Builds the shared fixture used by the relaxProteomicsGreedy tests below:
Expand Down
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