yeast 9.0.2

README.md

@@ -39,7 +39,7 @@ This repository contains the current consensus genome-scale metabolic model of _
 
 | Taxonomy | Latest update | Version | Reactions | Metabolites | Genes |
 |:-------|:--------------|:------|:------|:----------|:-----|
-| _Saccharomyces cerevisiae_ | 02-Dec-2023 | develop | 4130 | 2805 | 1162 |
+| _Saccharomyces cerevisiae_ | 23-Nov-2024 | develop | 4131 | 2806 | 1161 |
 
 # Installation & usage
 

code/increaseVersion.m

@@ -54,9 +54,7 @@ function increaseVersion(bumpType)
 disp('Running gene essentiality analysis')
 [new.accuracy,new.tp,new.tn,new.fn,new.fp] = essentialGenes(model);
 disp('Run growth analysis')
-new.R2=growth(model);
-
-saveas(gcf,'../../growth.png');
+new.R2=growth(model,true);
 
 cd ..
 copyfile('../README.md','backup.md')
@@ -134,7 +132,7 @@ function increaseVersion(bumpType)
                     disp(['NOTE: File ' diff_i{3} ' is changing more than expected'])
                     change = true;
                 end                
-            case {'history.md','README.md','growth.png','model/yeast-GEM.mat'}
+            case {'history.md','README.md','data/testResults/growth.png','model/yeast-GEM.mat','model/yeast-GEM.xlsx'}
             otherwise
                 disp(['NOTE: File ' diff_i{3} ' is changing'])
                 change = true;                

code/modelCuration/TEMPLATEcuration.m

@@ -48,15 +48,15 @@
 % Show some metrics:
 cd ../modelTests
 disp('Run gene essentiality analysis')
-[new.accuracy,new.tp,new.tn,new.fn,new.fp] = essentialGenes(model);
+[new.accuracy,new.tp,new.tn,new.fn,new.fp] = essentialGenes(model,true);
 fprintf('Genes in model: %d\n',numel(model.genes));
 fprintf('Gene essentiality accuracy: %.4f\n', new.accuracy);
 fprintf('True non-essential genes: %d\n', numel(new.tp));
 fprintf('True essential genes: %d\n', numel(new.tn));
 fprintf('False non-essential genes: %d\n', numel(new.fp));
 fprintf('False essential genes: %d\n', numel(new.fn));
 fprintf('\nRun growth analysis\n')
-R2=growth(model);
+R2=growth(model,true);
 fprintf('R2 of growth prediction: %.4f\n', R2);
 
 % Save model:

code/modelCuration/v9_0_2.m

@@ -0,0 +1,161 @@
+% This scripts applies curations to be applied on yeast-GEM release 9.0.1, to
+% get to yeast-GEM release 9.0.2.
+
+%% Load yeast-GEM 9.0.1 (requires local yeast-GEM git repository)
+cd ..
+codeDir=pwd();
+model = getEarlierModelVersion('9.0.1');
+model.id='yeastGEM_develop';
+model.version='';
+%dataDir=fullfile(pwd(),'..','data','modelCuration','v9.0.0'); % No dataDir required for these curations
+cd modelCuration
+
+%% Issue #371. Implement auxotrophy-based curation, as proposed by Han
+% et al., 2024 doi:10.1016/j.synbio.2024.07.006. Not all changes are
+% implemented as proposed by the authors.
+
+% To resolve AAT2 causing asparate auxotrophy
+model                       = setParam(model,'eq','r_0217',0);
+rxnIdx                      = getIndexes(model,'r_0217','rxns');
+model.rxnNotes{rxnIdx}      = 'No significant mitochondrial flux';
+model.rxnReferences{rxnIdx} = '10.1016/j.femsyr.2004.09.008';
+
+% To resolve ALD2 and ALD3 causing pantothenic acid auxotrophy
+model                       = changeGrRules(model,'r_0172','YMR170C or YMR169C',true);
+rxnIdx                      = getIndexes(model,'r_0172','rxns');
+model.rxnReferences{rxnIdx} = '10.1093/genetics/163.1.69';
+
+% To resolve CHO2 causing choline auxotrophy
+CHO2rxns                    = {'r_2488','r_2489','r_2490','r_2491','r_2492','r_2493','r_2494','r_2495'};
+model                       = changeGrRules(model,CHO2rxns,'YGR157W',true);
+rxnIdx                      = getIndexes(model,CHO2rxns,'rxns');
+model.rxnReferences(rxnIdx) = {'10.1016/0005-2760(90)90145-N'};
+% While the curation is correct, CHO2 and OPI3 are not strictly essential
+% genes, choline auxotrophy is only in relation to the production of
+% phosphocholines. If no cholines are available, the phospholipid
+% composition would be different. But because of the fixed biomass
+% composition in yeast-GEM, CHO2 and OPI3 act as essential genes. This
+% causes false positives in the essentialGenes function, as the genes not
+% truly essential.
+
+% To resolve CYS3 causing cysteine auxotrophy
+model                       = setParam(model,'eq','r_0312',0);
+rxnIdx                      = getIndexes(model,'r_0312','rxns');
+model.rxnNotes{rxnIdx}      = 'Regulatory role only';
+model.rxnReferences{rxnIdx} = '10.1111/j.1574-6968.2003.tb11531.x';
+
+% Han et al. suggest to block TUM1 reaction r_4703, to resolve CYS4 as
+% causing cysteine auxotrophy. However, there is good evidence that this
+% reaction is taking place (doi:10.1093/femsyr/fow100). Instead, make the
+% reaction irreversible.
+model                       = setParam(model,'lb','r_4703',0);
+
+% To resolve ERG10 causing ergosterol auxotrophy
+model = removeReactions(model,'r_0559',true,true); % ERG13, mitochondrial
+% only, see e.g. https://www.uniprot.org/uniprotkb/P54839/entry
+
+% To resolve GFA1 causing D-glucosamine auxotrophy: add chitin to
+% carbohydrate pseudoreaction and adjust other reactions proportionally
+rxn  = getIndexes(model,'r_4048','rxns');
+met1 = getIndexes(model,'s_0509','mets');%chitin
+met2 = getIndexes(model,'s_0001','mets');%(1->3)-beta-D-glucan
+met3 = getIndexes(model,'s_0004','mets');%(1->6)-beta-D-glucan
+met4 = getIndexes(model,'s_1107','mets');%mannan
+met5 = getIndexes(model,'s_0773','mets');%glycogen
+met6 = getIndexes(model,'s_1520','mets');%trehalose
+model.S(met1, rxn) = -0.02361;
+model.S(met2, rxn) = -0.73914;
+model.S(met3, rxn) = -0.24696;
+model.S(met4, rxn) = -0.70204;
+model.S(met5, rxn) = -0.35689;
+model.S(met6, rxn) = -0.13655;
+% And change gene association
+model = changeGrRules(model,'r_0477','YKL104C',true);
+
+% To resolve GSH1 causing glutatione auxotrophy: add glutathione to the
+% cofactor pseudoreaction
+rxn = getIndexes(model,'r_4598','rxns');
+met = getIndexes(model,'s_0750','mets');
+model.S(met, rxn) = -1e-06;
+% The above change will make GSH1 and GSH2 essential genes. This will be
+% reported in essentialGenes as false positives, as their essentiality is
+% debated (see for instance doi:10.1016/S1567-1356(02)00081-8). We here
+% argue that absence of glutathione very strongly affects cell growth and
+% stress tolerance.
+
+% To resolve ERG13/20 causing ergosterol auxotrophy; and HEM1/2/3/4/12 
+% causing heme auxotrophy. Heme transport and exchange should be present to
+% allow uptake if supplemented
+metsToAdd.metNames      = 'heme a';
+metsToAdd.compartments  = 'e';
+model                   = addMets(model,metsToAdd,true,'s_');
+model                   = addTransport(model,'c','e','heme a',true,false,'r_');
+model                   = addExchangeRxns(model,'out',model.mets(end));
+model.rxns(end)         = generateNewIds(model,'rxns','r_',1);
+model.rxnNames(end)     = {'heme a exchange'};
+model.subSystems{end}   = {'Exchange reaction'};
+
+% To resolve MET3 causing methionine auxotrophy
+rxnIdx = getIndexes(model,{'r_0223','r_0224','r_1026'},'rxns');
+model.eccodes(rxnIdx) = {'2.7.7.53','2.7.7.53','2.7.7.5'};
+% Han et al. suggest to block APA1 reaction r_1026, but their cited
+% reference (doi:10.1007/BF00264692) contains no reasoning for this.
+% Instead, there is good evidence for the function of this enzyme:
+% (doi:10.1128/jb.171.12.6437-6445.1989), although the reaction is assayed
+% in the reverse direction. So instead, invert the reaction (and keep it
+% irreversible), this has the same effect for MET3 as blocking it.
+model.S(:,rxnIdx(3)) = - model.S(:,rxnIdx(3));
+
+% To resolve MET13 causing methionine auxotrophy
+model = changeGrRules(model,'r_0080','(YGL125W and YPL023C) or YGL125W',true);
+
+% To resolve MET17 causing methionine auxotrophy
+model = setParam(model,'lb','r_0815',0);
+
+% To resolve THI4 causing thiamine auxotrophy and HOM2 causing methionine
+% and threonine auxotrophy
+model = removeReactions(model,'r_2070',true,true);
+model = removeReactions(model,'r_2071',true,true);
+rxnsToAdd.rxns      = generateNewIds(model,'rxns','r_',2);
+rxnsToAdd.equations = {'s_3910 + s_0803 => s_0423 + s_0293 + s_0456 + s_0794', ...
+                       's_1003 + s_1198 + s_0841 => s_1216 + s_3910 + 3 s_0803 + s_0794'};
+rxnsToAdd.rxnNames  = {'HET-P synthase (thiazole synthase)','adenylated thiazole synthase'};
+rxnsToAdd.lb        = [0,0];
+rxnsToAdd.ub        = [1000,1000];
+rxnsToAdd.eccodes   = {'','2.4.2.60'};
+rxnsToAdd.subSystems= {'Thiamine metabolism','Thiamine metabolism'};
+rxnsToAdd.grRules   = {'YGR144W','YGR144W'};
+rxnsToAdd.rxnMiriams{1} = struct('name',{{'kegg.reaction';'kegg.pathway';'metanetx.reaction'}},...
+                                'value',{{'R10685';'sce00730';'MNXR139808'}});
+rxnsToAdd.rxnMiriams{2} = struct('name',{{'kegg.reaction';'kegg.pathway';'metanetx.reaction'}},...
+                                'value',{{'R10711';'sce00730';'MNXR139812'}});
+rxnsToAdd.rxnReferences = {'10.1021/ja067606t','10.1021/ja067606t'};
+rxnsToAdd.rxnConfidenceScores = [3,3];
+model = addRxns(model,rxnsToAdd);
+
+% To resolve URA2 causing uracil auxotrophy
+model = changeGrRules(model,'r_0250','YJL130C or (YJR109C and YOR303W)',true);
+
+%% Issue #372. Correct UniProt identifier of YCR024C and YCR024C-A
+geneIdx = getIndexes(model,'YCR024C','genes');
+model.geneMiriams{geneIdx}.value = {'P25345'};
+
+%% DO NOT CHANGE OR REMOVE THE CODE BELOW THIS LINE.
+% Show some metrics:
+cd(fullfile(codeDir,'modelTests'))
+disp('Run gene essentiality analysis')
+[new.accuracy,new.tp,new.tn,new.fn,new.fp] = essentialGenes(model,true);
+fprintf('Genes in model: %d\n',numel(model.genes));
+fprintf('Gene essentiality accuracy: %.4f\n', new.accuracy);
+fprintf('True non-essential genes: %d\n', numel(new.tp));
+fprintf('True essential genes: %d\n', numel(new.tn));
+fprintf('False non-essential genes: %d\n', numel(new.fp));
+fprintf('False essential genes: %d\n', numel(new.fn));
+fprintf('\nRun growth analysis\n')
+R2=growth(model,true);
+fprintf('R2 of growth prediction: %.4f\n', R2);
+
+% Save model:
+cd ..
+saveYeastModel(model)
+cd modelCuration