[AGORA 1.03] Mitochondrion compartment in Clostridium difficile?
nigiord opened this issue · 4 comments
Hi there,
While looking at differences between AGORA 1.02 and 1.03, I noticed 4 new compartments in the latter:
Clostridium_difficile_CD196.xml: <compartment metaid="m" id="m" name="Mitochondrion" constant="false"/>
Clostridium_difficile_NAP07.xml: <compartment metaid="m" id="m" name="Mitochondrion" constant="false"/>
Clostridium_difficile_NAP08.xml: <compartment metaid="m" id="m" name="Mitochondrion" constant="false"/>
Clostridium_difficile_R20291.xml: <compartment metaid="m" id="m" name="Mitochondrion" constant="false"/>Each of those compartments only contains a single species: hydrogenphosphate (HO4P)
Clostridium_difficile_CD196.xml: <species metaid="M_pi__91__m__93__" id="M_pi__91__m__93__" name="hydrogenphosphate" compartment="m" hasOnlySubstanceUnits="false" boundaryCondition="false" constant="false" fbc:charge="-2" fbc:chemicalFormula="HO4P">
Clostridium_difficile_NAP07.xml: <species metaid="M_pi__91__m__93__" id="M_pi__91__m__93__" name="hydrogenphosphate" compartment="m" hasOnlySubstanceUnits="false" boundaryCondition="false" constant="false" fbc:charge="-2" fbc:chemicalFormula="HO4P">
Clostridium_difficile_NAP08.xml: <species metaid="M_pi__91__m__93__" id="M_pi__91__m__93__" name="hydrogenphosphate" compartment="m" hasOnlySubstanceUnits="false" boundaryCondition="false" constant="false" fbc:charge="-2" fbc:chemicalFormula="HO4P">
Clostridium_difficile_R20291.xml: <species metaid="M_pi__91__m__93__" id="M_pi__91__m__93__" name="hydrogenphosphate" compartment="m" hasOnlySubstanceUnits="false" boundaryCondition="false" constant="false" fbc:charge="-2" fbc:chemicalFormula="HO4P"><species metaid="M_pi__91__m__93__" id="M_pi__91__m__93__" name="hydrogenphosphate" compartment="m" hasOnlySubstanceUnits="false" boundaryCondition="false" constant="false" fbc:charge="-2" fbc:chemicalFormula="HO4P">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
<p>ChEBIID:43474</p>
</body>
</notes>
<annotation xmlns:sbml="http://www.sbml.org/sbml/level3/version1/core">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:vCard4="http://www.w3.org/2006/vcard/ns#" xmlns:bqbiol="http://biomodels.net/biology-qualifiers/" xmlns:bqmodel="http://biomodels.net/model-qualifiers/">
<rdf:Description rdf:about="#M_pi__91__m__93__">
<bqbiol:is>
<rdf:Bag>
<rdf:li rdf:resource="http://identifiers.org/hmdb/HMDB00973"/>
<rdf:li rdf:resource="http://identifiers.org/inchi/InChI=1S/H3O4P/c1-5(2,3)4/h(H3,1,2,3,4)/p-2"/>
<rdf:li rdf:resource="http://identifiers.org/kegg.compound/C00009"/>
<rdf:li rdf:resource="http://identifiers.org/pubchem.compound/1004"/>
</rdf:Bag>
</bqbiol:is>
</rdf:Description>
</rdf:RDF>
</annotation>
</species>This metabolite is only used in a single reaction (the same for each model):
<reaction metaid="R_IVCOASadp" id="R_IVCOASadp" name="Isovaleryl-CoA synthetase (ADP-forming)" reversible="true" fast="false" fbc:lowerFluxBound="FB1N1000" fbc:upperFluxBound="FB4N1000">
<notes>
<body xmlns="http://www.w3.org/1999/xhtml">
<p>Confidence Level: 0</p>
</body>
</notes>
<listOfReactants>
<speciesReference species="M_atp__91__c__93__" stoichiometry="1" constant="true"/>
<speciesReference species="M_coa__91__c__93__" stoichiometry="1" constant="true"/>
<speciesReference species="M_isoval__91__c__93__" stoichiometry="1" constant="true"/>
</listOfReactants>
<listOfProducts>
<speciesReference species="M_adp__91__c__93__" stoichiometry="1" constant="true"/>
<speciesReference species="M_ivcoa__91__c__93__" stoichiometry="1" constant="true"/>
<speciesReference species="M_pi__91__m__93__" stoichiometry="1" constant="true"/>
</listOfProducts>
<fbc:geneProductAssociation>
<fbc:geneProductRef fbc:geneProduct="G_645462__46__3__46__peg__46__2161"/>
</fbc:geneProductAssociation>
</reaction>- I tried to investigate but couldn't get a clue about the reason those compartment, metabolite or reaction are present. What's the story here? I guess it's something that wasn't properly curated out, but I'm curious about why such a compartment would be present in the original model in the first place. It was not present in AGORA 1.02.
- There is no reaction that consume hydrogenphosphate. Doesn't it mean it will accumulate in the system? Couldn't this be a problem in some simulations?
Thank you in advance for your help.
Best regards,
−Nils
Hi Nils,
this is due to a mismatch in the translation from Model SEED to VMH. We are going to fix that.
Currrently, this reaction is blocked so it has no effect on simulations.
Best,
Almut
Hi Almut and thank you for your answer,
So what you mean is that since M_pi__91__m__93__ is a dead-end metabolite, the reaction Isovaleryl-CoA synthetase (ADP-forming) is blocked. But to my understanding it can have some consequences on the simulations since M_isoval__91__c__93__ and M_ivcoa__91__c__93__ are used in other reactions in the models (so currently the models are equivalent to models that were knocked-out for this reaction). The consequence will probably depend on the overall importance of Isovaleryl-CoA and Isovaline for growth (I personally have no idea).
I guess we won't have a new AGORA 1.0x version soon, so as a temporary workaround do you think it is safe if I simply:
- remove the
mcompartment andM_pi__91__m__93__metabolite and, - replace in this reaction the
M_pi__91__m__93__metabolite by the cytoplasmic equivalentM_pi__91__c__93__?
Or will the fix be more complicated than that?
Best,
Nils
Hi Nils,
you can do that, but I will also update the repository with a new version.
best
Almut
Hi Almut,
Thank you very much, I'll just do that. Feel free to close this issue once the repository has been updated.
Best,
Nils