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Updated CFR code

scripts/constrain_flux_regulation_inconsistencies.m

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+function [fluxstate_gurobi,grate, solverobj, inconsistencies, model] =  constrain_flux_regulation_inconsistencies(model1,onreactions,offreactions,kappa,rho,epsilon,epsilon2,mode,minfluxflag)
+
+%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%
+if (~exist('mode','var')) || (isempty(mode))
+    mode = 1;
+end
+%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%
+if mode == 0 % genes
+    [~,~,onreactions,~] =  deleteModelGenes(model1, onreactions);
+    [~,~,offreactions,~] =  deleteModelGenes(model1, offreactions);
+end
+%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%
+if (~exist('epsilon','var')) || (isempty(epsilon))
+
+    epsilon = ones(size(onreactions))*1E-3;
+
+end
+
+if numel(epsilon) == 1
+
+    epsilon = repmat(epsilon, size(onreactions));
+
+end
+
+
+if (~exist('rho','var')) || (isempty(rho))
+
+    rho = repmat(1, size(onreactions));
+
+end
+
+if numel(rho) == 1
+
+    rho  = repmat(rho, size(onreactions));
+
+end
+
+if (~exist('kappa','var')) || (isempty(kappa))
+
+    kappa = repmat(1, size(offreactions));
+
+end
+
+if numel(kappa) == 1
+
+    kappa  = repmat(kappa, size(offreactions));
+
+end
+
+
+if (~exist('epsilon2','var')) || (isempty(epsilon2))
+      epsilon2 = zeros(size(offreactions));
+end
+
+if (~exist('minfluxflag','var')) || (isempty(minfluxflag))
+
+    minfluxflag = true; % by default sum of flux through all ractions is minimized
+
+end
+
+kappa1 = 1E-4; % minfluxflag
+params.outputflag = 0;
+params.iterationlimit = 1E6;
+offreactions_init = offreactions;  % store the original list of offreactions
+epsilon2_init = epsilon2;
+
+%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%
+if minfluxflag
+
+    kappa = [kappa(:); ones(size(setdiff(model1.rxns, offreactions)))*kappa1]; % minimize flux through all the reactions. PFBA
+    epsilon2 = [epsilon2; zeros(size(setdiff(model1.rxns, offreactions)))];
+    offreactions = [offreactions(:); setdiff(model1.rxns, offreactions)];
+
+end
+%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%
+% convert to gurobi format.
+model = model1;
+model.A = model1.S;
+model.obj = model1.c;
+model.rhs = model1.b;
+if exist('model1.csense','var') && ~isempty(model1.csense)
+    model.sense = model1.csense;
+    model.sense(ismember(model.sense,'E')) = '=';
+    model.sense(ismember(model.sense,'L')) = '<';
+    model.sense(ismember(model.sense,'G')) = '>';
+else
+    model.sense =repmat( '=',[size(model1.S,1),1]);
+end
+model.lb = model1.lb;
+model.ub = model1.ub;
+model.vtype = repmat('C',size(model1.S,2),1);
+model.modelsense = 'max';
+nrows = size(model.A,1);
+ncols = size(model.A,2);
+M = 10000;
+%epsilon2 = 0;
+objpos = find(model1.c);
+nrxns = length(model1.rxns);
+%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%
+% maximize the number of reactions with proteomic or transcriptomic evidence that are ON/up-regulated.
+for j = 1:length(onreactions)
+
+    rxnpos = find(ismember(model1.rxns,onreactions(j)));
+
+    %         xi - (eps + M)ti >= -M
+    % ti = 0 or 1.
+
+    rowpos = size(model.A,1) + 1;
+    colpos = size(model.A,2) + 1;
+    model.A(rowpos,rxnpos) = 1;
+    model.A(rowpos,colpos) = -(1*epsilon(j) + M);
+    model.rhs(rowpos) = -M;
+    model.sense(rowpos) = '>';
+    model.vtype(colpos) = 'B';
+    model.obj(colpos) = 1*rho(j);
+    model.lb(colpos) = 0;
+    model.ub(colpos) = 1;
+
+    % xi + (eps + M)ri <= M
+    % ri = 0 or 1.
+
+    rowpos = size(model.A,1) + 1;
+    colpos = size(model.A,2) + 1;
+
+    model.A(rowpos,rxnpos) = 1;
+    model.A(rowpos,colpos) = (1*epsilon(j) + M);
+    model.rhs(rowpos) = M;
+    model.sense(rowpos) = '<';
+    model.vtype(colpos) = 'B';
+    model.obj(colpos) = 1*rho(j);
+    model.lb(colpos) = 0;
+    model.ub(colpos) = 1;
+
+end
+
+%  constraints for off reactions. their flux is minimized.
+% soft constraints - can be violated if neccesary - i.e some reactions
+% can have some flux.  higher magnitude higher penalty
+
+for jj = 1:length(offreactions)
+    rxnpos = find(ismember(model1.rxns,offreactions(jj)));
+    %        xi + si >= -eps2
+    %     si >= 0
+    %     rho(ri + si)
+    % constraint 1
+    rowpos = size(model.A,1) + 1;
+    colpos = size(model.A,2) + 1;
+    model.A(rowpos,rxnpos) = 1;
+    model.A(rowpos,colpos) = 1;
+    model.rhs(rowpos) = -epsilon2(jj);
+    model.sense(rowpos) = '>';
+    model.vtype(colpos) = 'C';
+    % set si to be positive
+    model.lb(colpos) = 0;
+    model.ub(colpos) = 1000;
+    model.obj(colpos) = -1*kappa(jj); % minimized
+
+    % constraint 2
+    %     xi - ri <= eps2
+    %     ri >= 0
+    % new row and column
+    rowpos = size(model.A,1) + 1;
+    colpos = size(model.A,2) + 1;
+    model.A(rowpos,rxnpos) = 1;
+    model.A(rowpos,colpos) = -1;
+    model.rhs(rowpos) = epsilon2(jj);
+    model.sense(rowpos) = '<';
+    model.vtype(colpos) = 'C';
+    % set ri to be positive
+    model.lb(colpos) = 0;
+    model.ub(colpos) = 1000;
+    model.obj(colpos) = -1*kappa(jj); % minimized
+end
+
+solg1 = gurobi(model,params);
+try
+    fluxstate_gurobi = solg1.x(1:nrxns);
+    grate = solg1.x(objpos);
+    solverobj = solg1.objval;
+    %shadowprice = solg1.pi;
+
+
+    inconsistencies.totalon = length(onreactions);
+    inconsistencies.totaloff = length(offreactions_init);
+    if length(onreactions) > 0
+        [ix rxnpos] = ismember(onreactions, model1.rxns);
+        inconsistencies.on = sum(fluxstate_gurobi(rxnpos) < epsilon); % these are supposed to be above epsilon but they are below
+    else
+        inconsistencies.on = NaN;
+    end
+
+    if length(offreactions_init) > 0
+        [ix rxnpos] = ismember(offreactions_init, model1.rxns);
+        inconsistencies.off = sum(fluxstate_gurobi(rxnpos) > epsilon2_init); % these are supposed to be below epsilon2 but are higher
+    else
+        inconsistencies.off  = NaN;
+    end
+
+
+catch
+    fluxstate_gurobi = NaN;
+    grate = NaN;
+    solverobj = NaN;
+      inconsistencies.off  = NaN;
+       inconsistencies.on = NaN;
+end
+
+end
+