Merge pull request #2271 from ThummaratPaklao/addfile_icongems

Addfile icongems

Author: rmtfleming

src/analysis/ICONGEMs/ICONGEMs.m

@@ -0,0 +1,302 @@
+function [solICONGEMs, boundEf] = ICONGEMs(model, exp, genetxt, condition, threshold, alpha)
+% Algorithm to Integrate a Gene Co-expression Network and Genome-scale Metabolic Model:
+% This algorithm calculates the reaction flux distribution for each condition by applying 
+% quadratic programming.
+%
+% USAGE:
+%
+%    [solICONGEMs, boundEf] = ICONGEMs(model, exp, genetxt, condition, threashold, alpha)
+%
+% INPUTS:
+%
+%    model:           input model (COBRA model structure)
+%    exp:             expression profile corresponding to the gene names that 
+%                     extract from gene expression profile file
+%    genetxt:         list of gene names that extract from gene expression profile
+%                     file
+%
+% OPTIONAL INPUTS:
+%    threshold:           The value of the correlation coefficient for constructing 
+%                         the co-expression network (default value: 0.9).
+%    condition:           Row vector indicating the number of conditions 
+%                         corresponding to the conditions in exp 
+%                         (default value: 1:size(exp, 2)).
+%    alpha:               The value for the proportion of biomass (default value: 1).
+%                         
+% OUTPUTS:
+%    solICONGEMs:             Flux distribution table corresponding to reaction flux names.
+%    boundEf:                 Upper bound of E-flux.
+%
+% EXAMPLES:
+%    % This could be an example that can be copied from the documentation to MATLAB:
+%    solution = ICONGEMs(model, exp, genetxt, condition, threashold, alpha)
+%    % without optional values:
+%    solution = ICONGEMs(model, exp, genetxt)
+%
+%..Author: 
+%    -Thummarat Paklao, 01/02/2024, Department of Mathematics and Computer Science, Faculty of Science, Chulalongkorn University, Thailand. 
+%    -Apichat Suratanee, 01/02/2024, Department of Mathematics, Faculty of Applied Science, King Mongkut's University of Technology North Bangkok. 
+%    -Kitiporn Plaimas, 01/02/2024, Department of Mathematics and Computer Science, Faculty of Science, Chulalongkorn University, Thailand.    
+
+if (nargin < 4 || isempty(condition))
+      condition = 1:size(exp, 2);
+end
+if (nargin < 5 || isempty(threshold))
+      threshold = 0.9;
+end
+if (nargin < 6 || isempty(alpha))
+      alpha = 0.99;
+end
+
+% construct the template model
+
+modelN = model;
+modelN.lb(modelN.lb >= 0) = 0;
+modelN.lb(modelN.lb < 0) = -1000;
+modelN.ub(modelN.ub <= 0) = 0;
+modelN.ub(modelN.ub > 0) = 1000;
+
+% convert to irreversible format
+
+[modelIrrev, matchRev, rev2irrev, irrev2rev] = convertToIrreversible(modelN);
+
+% Check that the gene names in the gene expression profile agree with 
+% the gene names in the metabolic model.
+
+geneinMet = zeros(size(genetxt, 1) - 1, 1);
+for i = 2:size(genetxt, 1)
+    for j = 1:size(modelIrrev.genes, 1)
+        if string(genetxt(i)) == string(modelIrrev.genes(j))
+            geneinMet(i - 1) = 1;
+        end
+    end
+end
+if sum(sum(geneinMet)) == 0
+    disp("gene name in gene expression data is not agree gene name in metabolic model")
+end
+
+% Choose only the gene expression profiles that match genes in the metabolic model.
+
+exp1 = exp(geneinMet == 1, :);
+txt2 = genetxt([0; geneinMet] == 1, 1);
+
+% remove missing data
+
+[exp1, TF] = rmmissing(exp1, 1);
+txt2 = txt2(~TF, 1);
+geneincoexnet = modelIrrev.genes(~TF);
+
+% Construct co-expression network 
+
+cor = corr((exp1)');
+cor1 = cor >= threshold;
+
+% Find gene pairs that have a high correlation in the co-expression network.
+
+indCorGene = zeros(1, 2);
+l = 1;
+for i = 1:size(cor, 1)
+    for j = i:size(cor,1)
+        if (cor1(i,j) ~= 0) && (i ~= j)
+            indCorGene(l, 1) = i;
+            indCorGene(l, 2) = j;
+            l = l + 1;
+         end
+    end
+end
+
+coGene = cell(size(indCorGene, 1), 2);
+coGene(:, 1) = geneincoexnet(indCorGene(:, 1), 1);
+coGene(:, 2) = geneincoexnet(indCorGene(:, 2), 1);
+
+NameRxn={};
+for i = 1:size(modelIrrev.genes)
+    [z1, NameRxn{i}] = findRxnsFromGenes(modelIrrev, modelIrrev.genes(i, 1), [], 1);
+end
+
+% Find reactions that correspond to the gene
+
+NameCorRxn = {};
+for i = 1:size(coGene, 1)
+    NameCorRxn{i, 1} = NameRxn{find(modelIrrev.genes == string(coGene(i, 1)))};
+    NameCorRxn{i, 2} = NameRxn{find(modelIrrev.genes == string(coGene(i, 2)))};
+end
+
+f = 0;
+h = 0;
+indCorRxn = zeros(10, 2);
+for i = 1:size(NameCorRxn, 1)
+    if (~isempty(NameCorRxn{i, 1}) && ~isempty(NameCorRxn{i, 2}))
+    for j = 1:size(NameCorRxn{i, 1}, 1)
+        f = f + size(NameCorRxn{i, 2}, 1);
+        indCorRxn(h + 1 : h + size(NameCorRxn{i, 2}, 1), 1) = findRxnIDs(modelIrrev, NameCorRxn{i, 1}{j, 1}); 
+            for w = 1:size(NameCorRxn{i, 2}, 1)
+                indCorRxn(h + w,2)=findRxnIDs(modelIrrev,NameCorRxn{i, 2}{w, 1}); 
+            end
+            h = f;
+    end
+    end
+end
+
+% Construct a reaction pair matrix.
+
+R = zeros(length(modelIrrev.rxns),length(modelIrrev.rxns));
+for i = 1:size(indCorRxn, 1)
+    if indCorRxn(i, 1) ~= indCorRxn(i, 2)
+        R(indCorRxn(i, 1), indCorRxn(i, 2)) = 1;       
+    end
+end
+
+% Construct an irreversible reaction matrix from the reversible reactions 
+% that are decomposed into the same components.
+
+Re = zeros(size(R));
+for i = 1:length(model.rxns)
+    if length(rev2irrev{i, 1}) == 2
+        Re(i, rev2irrev{i,1}(2)) = 1;
+    end
+end
+
+% Process gene expression data based on Gene-Protien-Reaction (GPR) associations.
+
+geneExdat = zeros(length(modelIrrev.genes), 1);
+nupb = zeros(length(modelIrrev.rules), size(exp, 2));
+for ch = 1:size(exp, 2)
+for i = 1:length(modelIrrev.genes)
+    cc = 0;
+    for j = 1:length(genetxt(:, 1)) - 1
+        if string(modelIrrev.genes(i)) == string(genetxt(j + 1, 1))
+            geneExdat(i) = exp(j, ch);
+            cc = cc + 1;
+        end
+    end
+    if geneExdat(i) == 0 && cc == 0
+        geneExdat(i) = 1000;
+    end
+end
+
+for i = 1:length(modelIrrev.rules)
+    rulegene = modelIrrev.rules{i};
+    if isempty(rulegene)
+        rsum = 1000;
+    else
+        newrule = split(rulegene,"|");
+        nrule = size(newrule, 1);
+        rsum = 0;
+        for j = 1:nrule
+            newrule1 = newrule{j};
+            nnrule = length(newrule1);
+            rmin = inf;
+            for k = 1:nnrule
+                if newrule1(k) == 'x'
+                    r1 = k+2;
+                end
+                if (newrule1(k) == ')' && newrule1(k-1) ~= ' ' && newrule1(k - 1) ~= ')')
+                    rmin = min(rmin, geneExdat(str2num(convertCharsToStrings((newrule1(r1:k - 1))))));
+                end    
+            end
+            rsum = rsum + rmin;
+        end 
+    end
+    nupb(i, ch) = rsum;
+end
+
+end
+PosNupb = nupb >= 1000;
+nupb(PosNupb) = max(nupb(~PosNupb));
+
+% Construct a table for reporting the results
+
+solution = table(model.rxns);
+solutionFull = table(modelIrrev.rxns);
+solutionEf = table(model.rxns);
+solutionEfFull = table(modelIrrev.rxns);
+n = 0;
+ 
+% Construct the model and calculate the flux distribution.
+
+for ch = condition
+    n = n + 1;
+disp("Condition :"); disp(ch);
+model3 = changeRxnBounds(modelIrrev,modelIrrev.rxns, nupb(:, ch), 'u');
+solution1 = optimizeCbModel(model3);
+
+Trans0 = zeros(size(modelIrrev.mets, 1),size(modelIrrev.rxns, 1));
+Trans2 = -1 * eye(size(modelIrrev.rxns, 1));
+S2 = zeros(size(modelIrrev.rxns, 1));
+for i = 1:length(modelIrrev.rxns)
+    S2(i, i) = 1 / max(nupb(i, :));
+end
+
+
+Obj4 = [modelIrrev.c' zeros(1, size(modelIrrev.rxns, 1))] ;
+
+lob = [model3.lb; (-1) * inf * ones(size(modelIrrev.rxns, 1), 1)];
+upb = [model3.ub; inf * ones(size(modelIrrev.rxns, 1), 1)];
+
+O = [zeros(size(R)) zeros(size(R)); zeros(size(R)) R]; 
+Aeq = [modelIrrev.S Trans0; S2 Trans2; Obj4]; 
+beq = [zeros(size(modelIrrev.mets, 1), 1); (-1) * ones(size(modelIrrev.rxns,1),1); alpha * solution1.f];
+
+model2 = struct;
+model2.lb = lob;
+model2.ub = upb; 
+model2.A = sparse(Aeq);
+model2.sense = [char('=' * ones(size(model2.A,1) - 1, 1)) ; char('>')]; 
+model2.rhs = beq;
+model2.modelsense = 'min'; 
+numrxn = [1:length(modelIrrev.rxns)]; 
+j = 1;
+for i = 1:length(model.rxns)
+    if length(Re(Re(i, :)>0)) == 1
+model2.quadcon(j).Qrow = i;
+model2.quadcon(j).Qcol = numrxn(Re(i, :)>0);
+model2.quadcon(j).Qval = 1.0;
+model2.quadcon(j).rhs = 0.0;
+model2.quadcon(j).q = sparse(zeros(2*size(Re, 1), 1));
+model2.quadcon(j).sense = '=';
+j = j + 1;
+    end
+end
+model2.Q = sparse(O);
+params.NonConvex = 2;
+result = gurobi(model2, params);
+x = result.x;
+solutionFull(:, n + 1) = table(x(1:size(modelIrrev.rxns),1));
+solutionEfFull(:, n + 1) = table(solution1.x);
+solFlux = [];
+solFluxEf = [];
+for i = 1:length(model.rxns)
+    if length(rev2irrev{i, 1}) == 1
+        solFlux(i, 1) = x(i, 1);
+        solFluxEf(i, 1) = solution1.x(i, 1);
+    else
+        solFlux(i, 1) = (x(rev2irrev{i, 1}(1, 1))-x(rev2irrev{i, 1}(1, 2)));
+        solFluxEf(i, 1) = (solution1.x(rev2irrev{i, 1}(1, 1))-solution1.x(rev2irrev{i, 1}(1, 2)));
+        if solFluxEf(i, 1)>=0
+            solutionEfFull{rev2irrev{i, 1}(1, 1), n + 1} = solFluxEf(i, 1);
+            solutionEfFull{rev2irrev{i, 1}(1, 2), n + 1} = 0;
+        elseif solFluxEf(i, 1)<0
+            solutionEfFull{rev2irrev{i, 1}(1, 1), n + 1} = 0;
+            solutionEfFull{rev2irrev{i, 1}(1, 2), n + 1} = abs(solFluxEf(i, 1));
+
+        end
+    end
+end
+solution(:, n + 1) = table(solFlux);
+solutionEf(:, n + 1) = table(solFluxEf);
+
+end
+boundEf = table(nupb);
+solICONGEMs.sol = solution;
+solICONGEMs.solRev = solutionFull;
+
+solEflux.sol = solutionEf;
+solEflux.solRev = solutionEfFull;
+
+% Export the results
+
+filename = 'result.csv';
+writetable(solution, filename)
+end
+

src/analysis/ICONGEMs/readme.md

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+

test/additionalTests/testICONGEMs/readme.md

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+

test/additionalTests/testICONGEMs/testICONGEMs.m

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+% The COBRAToolbox: testICONGEMs.m
+%
+% Purpose:
+%     - Tests the ICONGEMs function 
+%
+%..Author: 
+%    -Original file, Thummarat Paklao, Apichat Suratanee, and Kitiporn Plaimas. 
+
+global CBTDIR
+
+% set the tolerance
+tol = 1e-4;
+tol2 = 2e-1;
+
+% define the solver required to run the test
+useIfAvailable = {'gurobi'};
+
+% test solver packages
+solverPkgs = prepareTest('needsLP', true, 'needsQP', true, 'useSolversIfAvailable', useIfAvailable);
+
+% save the current path
+currentDir = pwd;
+
+% initialize the test
+fileDir = fileparts(which('testICONGEMs'));
+cd(fileDir);
+
+% load model
+modelFileName = 'ecoli_core_model.mat';
+model = getDistributedModel(modelFileName); 
+[modelIrrev, matchRev, rev2irrev, irrev2rev] = convertToIrreversible(model);
+Re = zeros(size(modelIrrev.rxns,1),size(modelIrrev.rxns,1));
+for i = 1:length(model.rxns)
+    if length(rev2irrev{i, 1}) == 2
+        Re(i, rev2irrev{i,1}(2)) = 1;
+    end
+end
+
+% load gene expression data
+fileName = 'gene_exp.csv';
+[exp, txt] = xlsread(fileName);
+
+% set optional parameter
+condition1=1:size(exp,2);
+threashold = 0.8;
+alpha = 0.99;
+
+% test optimizeCbModel in cobratoolbox
+
+sol_fba = optimizeCbModel(model);
+
+for k = 1:length(solverPkgs.QP)
+    fprintf(' -- Running testICONGEMs using the solver interface: %s ... ', solverPkgs.QP{k});
+
+    solverQPOK = changeCobraSolver(solverPkgs.QP{k}, 'QP', 0);
+
+    if solverQPOK
+        [solICONGEMs, solEflux, R, boundEf] = ICONGEMs(model, exp, txt);
+        for i = 1:size(exp,2)
+            assert(norm(model.S * table2array(solICONGEMs.sol(:,i+1)) - model.b, 2) < tol);
+            assert(abs(table2array(solICONGEMs.solRev(:,i+1))' * Re * table2array(solICONGEMs.solRev(:,i+1))) < tol)
+            assert(abs(model.c' * table2array(solICONGEMs.sol(:,i+1)) - alpha * model.c' * table2array(solEflux.sol(:,i+1))) < tol)
+
+        end
+
+    end
+    
+    % output a success message
+    fprintf('Done.\n');
+end
+
+% change the directory
+cd(currentDir)