-
Notifications
You must be signed in to change notification settings - Fork 46
Commit
This commit does not belong to any branch on this repository, and may belong to a fork outside of the repository.
- Loading branch information
Showing
20 changed files
with
35,227 additions
and
33,901 deletions.
There are no files selected for viewing
This file contains bidirectional Unicode text that may be interpreted or compiled differently than what appears below. To review, open the file in an editor that reveals hidden Unicode characters.
Learn more about bidirectional Unicode characters
This file contains bidirectional Unicode text that may be interpreted or compiled differently than what appears below. To review, open the file in an editor that reveals hidden Unicode characters.
Learn more about bidirectional Unicode characters
This file contains bidirectional Unicode text that may be interpreted or compiled differently than what appears below. To review, open the file in an editor that reveals hidden Unicode characters.
Learn more about bidirectional Unicode characters
This file contains bidirectional Unicode text that may be interpreted or compiled differently than what appears below. To review, open the file in an editor that reveals hidden Unicode characters.
Learn more about bidirectional Unicode characters
| Original file line number | Diff line number | Diff line change |
|---|---|---|
| @@ -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 |
Oops, something went wrong.