Description of getModelFromKEGG

0001 function [model,KOModel]=getModelFromKEGG(keggPath,keepSpontaneous,...
0002     keepUndefinedStoich,keepIncomplete,keepGeneral)
0003 % getModelFromKEGG
0004 %   Retrieves information stored in KEGG database and generates a model
0005 %
0006 %   Input:
0007 %   keggPath            if keggGenes.mat, keggMets.mat, keggPhylDist.mat or
0008 %                       keggRxns.mat are not in the RAVEN/external/kegg
0009 %                       directory, this function will attempt to read data
0010 %                       from a local FTP dump of the KEGG database.
0011 %                       keggPath is the path to the root of this database
0012 %                       (optional, default 'RAVEN/external/kegg'). If
0013 %                       keggModel.mat is present in the same directory, the
0014 %                       function reads the data from this file and ignores
0015 %                       keggGenes.mat, keggMets.mat and keggRxns.mat
0016 %   keepSpontaneous     include reactions labeled as "spontaneous" (optional,
0017 %                       default true)
0018 %   keepUndefinedStoich include reactions in the form n A <=> n+1 A. These
0019 %                       will be dealt with as two separate metabolites
0020 %                       (optional, default true)
0021 %   keepIncomplete      include reactions which have been labelled as
0022 %                       "incomplete", "erroneous" or "unclear" (optional,
0023 %                       default true)
0024 %   keepGeneral         include reactions which have been labelled as
0025 %                       "general reaction". These are reactions on the form
0026 %                       "an aldehyde <=> an alcohol", and are therefore
0027 %                       unsuited for modelling purposes. Note that not all
0028 %                       reactions have this type of annotation, and the
0029 %                       script will therefore not be able to remove all
0030 %                       such reactions (optional, default false)
0031 %
0032 %   Output:
0033 %   model               a model structure generated from the database. All
0034 %                       reactions and the metabolites used in them will be
0035 %                       added
0036 %   KOModel             a model structure representing the KEGG Orthology
0037 %                       ids and their associated genes. The KO ids are
0038 %                       saved as reactions
0039 %
0040 %   NOTE: The model output from getModelFromKEGG can be used as template
0041 %   for fillGaps. In that case, ensure that the genes and rxnGeneMat fields
0042 %   are removed before parsing: model=rmfield(model,'genes'), etc.
0043 %
0044 % Usage: [model,KOModel]=getModelFromKEGG(keggPath,keepSpontaneous,...
0045 %    keepUndefinedStoich,keepIncomplete,keepGeneral)
0046 
0047 if nargin<1
0048     keggPath='RAVEN/external/kegg';
0049 else
0050     keggPath=char(keggPath);
0051 end
0052 if nargin<2
0053     keepSpontaneous=true;
0054 end
0055 if nargin<3
0056     keepUndefinedStoich=true;
0057 end
0058 if nargin<4
0059     keepIncomplete=true;
0060 end
0061 if nargin<5
0062     keepGeneral=false;
0063 end
0064 
0065 ravenPath=findRAVENroot();
0066 modelFile=fullfile(ravenPath,'external','kegg','keggModel.mat');
0067 if exist(modelFile, 'file') && isNewestFile(ravenPath)
0068     fprintf(['Importing the global KEGG model from ' strrep(modelFile,'\','/') '... ']);
0069     load(modelFile);
0070     fprintf('COMPLETE\n');
0071 else
0072     fprintf(['NOTE: The file ' strrep(modelFile,'\','/') ' does not exist or is out-of-date and therefore will be (re)generated\n']);
0073     %First get all reactions
0074     [model,isSpontaneous,isUndefinedStoich,isIncomplete,isGeneral]=getRxnsFromKEGG(keggPath);
0075     
0076     %Get the KO ids that are associated with any of the reactions. They
0077     %will be used later on to create a rxn-gene matrix
0078     KOs=cell(numel(model.rxns)*2,1);
0079     %Make room for two KO ids per reaction
0080     
0081     addToIndex=1;
0082     %Add all KO ids that are used
0083     for i=1:numel(model.rxns)
0084         if isstruct(model.rxnMiriams{i})
0085             for j=1:numel(model.rxnMiriams{i}.name)
0086                 if strcmpi('kegg.orthology',model.rxnMiriams{i}.name{j})
0087                     %Add the KO id
0088                     KOs(addToIndex)=model.rxnMiriams{i}.value(j);
0089                     addToIndex=addToIndex+1;
0090                 end
0091             end
0092         end
0093     end
0094     
0095     KOs=KOs(1:addToIndex-1);
0096     KOs=unique(KOs);
0097     
0098     %Get all genes from any organism in KEGG that is associated with any of
0099     %the KOs
0100     KOModel=getGenesFromKEGG(keggPath,KOs);
0101     
0102     fprintf('Pruning the global KEGG model from the partially annotated, lumped KEGG Orthology entries... ')
0103     model.genes=KOModel.genes;
0104     
0105     %It can be that there are KOs from the reactions that have no database
0106     %entry. These are (as far as I have seen) lumped versions of other KOs
0107     %and should be removed
0108     KOsToRemove=setdiff(KOs, KOModel.rxns);
0109     
0110     %Loop through all reactions and delete the KOs that were not found
0111     for i=1:numel(model.rxns)
0112         if isstruct(model.rxnMiriams{i})
0113             for j=1:numel(model.rxnMiriams{i}.name)
0114                 toDel=[];
0115                 if strcmp(model.rxnMiriams{i}.name{j},'kegg.orthology')
0116                     if ismember(model.rxnMiriams{i}.value{j},KOsToRemove)
0117                         toDel=[toDel;j];
0118                     end
0119                 end
0120             end
0121             %Delete the KOs
0122             if any(toDel)
0123                 %If all posts are deleted, then delete the whole structure
0124                 if numel(toDel)==j
0125                     model.rxnMiriams{i}=[];
0126                 else
0127                     model.rxnMiriams{i}.name(toDel)=[];
0128                     model.rxnMiriams{i}.value(toDel)=[];
0129                 end
0130             end
0131         end
0132     end
0133     fprintf('COMPLETE\n');
0134     
0135     fprintf('Constructing the rxnGeneMat for the global KEGG model...   0%% complete');
0136     %Create the rxnGeneMat for the reactions. This is simply done by
0137     %merging the gene associations for all the involved KOs
0138     r=zeros(10000000,1);
0139     %Store the positions since it's slow to write to a sparse array in a
0140     %loop
0141     c=zeros(10000000,1);
0142     counter=1;
0143     for i=1:numel(model.rxns)
0144         if isstruct(model.rxnMiriams{i})
0145             I=strncmp('kegg.orthology',model.rxnMiriams{i}.name,18);
0146             if any(I)
0147                 [J, K]=ismember(model.rxnMiriams{i}.value(I),KOModel.rxns);
0148                 %Find all gene indexes that correspond to any of these KOs
0149                 [~, L]=find(KOModel.rxnGeneMat(K(J),:));
0150                 if any(L)
0151                     %Allocate room for more elements if needed
0152                     if counter+numel(L)-1>=numel(r)
0153                         r=[r;zeros(numel(r),1)];
0154                         c=[c;zeros(numel(c),1)];
0155                     end
0156                     r(counter:counter+numel(L)-1)=ones(numel(L),1)*i;
0157                     c(counter:counter+numel(L)-1)=L(:);
0158                     counter=counter+numel(L);
0159                 end
0160             end
0161         end
0162         if rem(i-1,100) == 0
0163             progress=pad(num2str(floor(i/numel(model.rxns)*100)),3,'left');
0164             fprintf('\b\b\b\b\b\b\b\b\b\b\b\b\b%s%% complete',progress);
0165         end
0166     end
0167     
0168     model.rxnGeneMat=sparse(r(1:counter-1),c(1:counter-1),ones(counter-1,1));
0169     if size(model.rxnGeneMat,1)~=numel(model.rxns) || size(model.rxnGeneMat,2)~=numel(KOModel.genes)
0170         model.rxnGeneMat(numel(model.rxns),numel(KOModel.genes))=0;
0171     end
0172     fprintf('\b\b\b\b\b\b\b\b\b\b\b\b\bCOMPLETE\n');
0173     
0174     %Then get all metabolites
0175     metModel=getMetsFromKEGG(keggPath);
0176     
0177     fprintf('Finalizing the global KEGG model... ');
0178     %Add information about all metabolites to the model
0179     [a, b]=ismember(model.mets,metModel.mets);
0180     a=find(a);
0181     b=b(a);
0182     
0183     if ~isfield(model,'metNames')
0184         model.metNames=cell(numel(model.mets),1);
0185         model.metNames(:)={''};
0186     end
0187     model.metNames(a)=metModel.metNames(b);
0188     
0189     if ~isfield(model,'metFormulas')
0190         model.metFormulas=cell(numel(model.mets),1);
0191         model.metFormulas(:)={''};
0192     end
0193     model.metFormulas(a)=metModel.metFormulas(b);
0194     
0195     if ~isfield(model,'inchis')
0196         model.inchis=cell(numel(model.mets),1);
0197         model.inchis(:)={''};
0198     end
0199     model.inchis(a)=metModel.inchis(b);
0200     
0201     if ~isfield(model,'metMiriams')
0202         model.metMiriams=cell(numel(model.mets),1);
0203     end
0204     model.metMiriams(a)=metModel.metMiriams(b);
0205     
0206     %The composition should be loaded from InChIs when available
0207     I=find(~cellfun(@isempty,model.inchis));
0208     for i=1:numel(I)
0209         S=regexp(model.inchis(I(i)),'/','split');
0210         S=S{1};
0211         if numel(S)>=2
0212             %Don't copy if it doesn't look good
0213             model.metFormulas(I(i))=S(2);
0214         end
0215     end
0216     
0217     %Put all metabolites in one compartment called 's' (for system). This
0218     %is done just to be more compatible with the rest of the code
0219     model.comps={'s'};
0220     model.compNames={'System'};
0221     model.metComps=ones(numel(model.mets),1);
0222     
0223     %If reactions with undefined stoichiometry are kept, then the
0224     %corresponding metabolites will have ids such as "(n+1) C00001" and
0225     %their names will be empty. These ids are not valid SBML identifiers
0226     %and are therefore replaced with "undefined1, undefined2...". The
0227     %former ids are stored as the new names
0228     I=find(cellfun(@any,strfind(model.mets,'n')) | cellfun(@any,strfind(model.mets,'m')));
0229     model.metNames(I)=model.mets(I);
0230     repNums=1:numel(I);
0231     repIDs=strcat('undefined_',cellfun(@num2str,num2cell(repNums(:)),'UniformOutput',false));
0232     model.mets(I)=repIDs;
0233     
0234     %It could also be that the metabolite names are empty for some other
0235     %reason. In that case, use the ID instead
0236     I=cellfun(@isempty,model.metNames);
0237     model.metNames(I)=model.mets(I);
0238 
0239     %Deafult LB and UB
0240     model.annotation.defaultLB = -1000;
0241     model.annotation.defaultUB = 1000;
0242     
0243     %Save the model structure
0244     save(modelFile,'model','KOModel','isGeneral','isIncomplete','isUndefinedStoich','isSpontaneous');
0245     fprintf('COMPLETE\n');
0246 end
0247 
0248 %Delete reactions which are labeled as "incomplete", "erroneous",
0249 %"unclear", "general reaction" or having undefined stoichiometry (depending
0250 %on settings)
0251 if keepSpontaneous==false
0252     model=removeReactions(model,intersect(isSpontaneous,model.rxns),true,true);
0253 end
0254 if keepUndefinedStoich==false
0255     model=removeReactions(model,intersect(isUndefinedStoich,model.rxns),true,true);
0256 end
0257 if keepIncomplete==false
0258     model=removeReactions(model,intersect(isIncomplete,model.rxns),true,true);
0259 end
0260 if keepGeneral==false
0261     model=removeReactions(model,intersect(isGeneral,model.rxns),true,true);
0262 end
0263 
0264 end
0265 
0266 function output = isNewestFile(ravenPath)
0267 %The ad hoc function, which checks whether keggModel.mat is the more
0268 %recently modified than keggRxns.mat, keggGenes.mat and keggRxns.mat
0269 modelFile=fullfile(ravenPath,'external','kegg','keggModel.mat');
0270 rxnsFile=fullfile(ravenPath,'external','kegg','keggRxns.mat');
0271 genesFile=fullfile(ravenPath,'external','kegg','keggGenes.mat');
0272 metsFile=fullfile(ravenPath,'external','kegg','keggMets.mat');
0273 if (getFileTime(modelFile)>getFileTime(rxnsFile))&&...
0274         (getFileTime(modelFile)>getFileTime(genesFile))&&...
0275         (getFileTime(modelFile)>getFileTime(metsFile))
0276     output=1;
0277 else
0278     output=0;
0279 end
0280 end
0281 
0282 function modTime = getFileTime(fileName)
0283 %Gets a last modification time for a particular file in datenum format that
0284 %the numbers could be easily compared for different files
0285 listing = dir(fileName);
0286 assert(numel(listing) == 1, 'No such file: %s', fileName);
0287 modTime = listing.datenum;
0288 format long;
0289 end
getModelFromKEGG

PURPOSE

SYNOPSIS

DESCRIPTION

CROSS-REFERENCE INFORMATION

SUBFUNCTIONS

SOURCE CODE
