The Subliminal Toolbox: automating steps in the reconstruction of metabolic networks

The Subliminal Toolbox: automating steps in the reconstruction of metabolic networks Neil Swainston Manchester Centre for Integrative Systems Biology Integrative Bioinformatics 2011, Wageningen, Netherlands 22 March 2011

Metabolic networks ,[object Object],[object Object],[object Object],[object Object],[object Object]

Metabolic networks Metabolic reactions A + B C + D Gene / enzyme E1 Protonation C + DH + Mass balancing A + 2B + H + A ext Extracellular Intracellular Transport reactions Mitochondria Cytosol C m Compartmentalisation biomass aa nucl Biomass objective T1 ,[object Object]

How are they generated? ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

Automation ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

KEGG MetaCyc Merge pathways Balance reactions Add transport reactions Draft (De)protonate metabolites Balance reactions (De)protonate metabolites Merge Add compartmentalisation Add biomass reaction

Initial draft ,[object Object],[object Object],[object Object],[object Object]

Naming ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

MIRIAM annotation <species metaid="_glc" id="glc" name="D-Glucose"> </species>

MIRIAM annotation <species metaid="_glc" id="glc" name="D-Glucose"> <annotation> <rdf:RDF> <rdf:Description rdf:about="#_glc"> <bqbiol:is> <rdf:Bag> <rdf:li rdf:resource=" urn:miriam:obo.chebi:CHEBI:17634 "/> </rdf:Bag> </bqbiol:is> </rdf:Description> </rdf:RDF> </annotation> </species>

Exploiting model annotations ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

UniProt ChEBI KEGG libAnnotationSBML MIRIAM / RDF annotation Molecular formula, protein sequence, etc.

Merging ,[object Object],[object Object],[object Object]

Charge state determination ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],✓ ✗

Stereochemistry ,[object Object],[object Object],beta-D-glucose D-glucose

Stereochemistry-induced gaps X Y

ChEBI ontology ,[object Object]

Reaction balancing ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

Reaction balancing carbon dioxide + 2-Acetolacetate  Pyruvate Ab = 0 A = b represents a vector of stoichiometries CO 2 + C 5 H 7 O 4 -  C 3 H 3 O 3 - Reactants Products Optional reactants Optional products CO2 C5H7O4 C3H3O3 H+ H20 H+ H20 CO2 C 1 5 -3 0 0 0 0 -1 O 2 4 -3 0 1 0 -1 -2 H 0 7 -3 1 2 -1 -2 0 charge 0 -1 1 1 0 -1 0 0 b min 1 1 1 0 0 0 0 0

Reaction balancing ,[object Object],carbon dioxide + 2-Acetolacetate  2 Pyruvate + H + CO 2 + C 5 H 7 O 4 -  2 C 3 H 3 O 3 - + H + Reactants Products Optional reactants Optional products CO2 C5H7O4 C3H3O3 H+ H20 H+ H20 CO2 C 1 5 -3 0 0 0 0 -1 O 2 4 -3 0 1 0 -1 -2 H 0 7 -3 1 2 -1 -2 0 charge 0 -1 1 1 0 -1 0 0 b min 1 1 1 0 0 0 0 0 b 1 1 2 0 0 1 0 0

Compartmentalisation ,[object Object],[object Object],[object Object],[object Object],[object Object]

Biomass function ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

Analysis ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

Analysis ,[object Object],[object Object],[object Object],[object Object],[object Object],Components Subliminal Manual Compartments 7 17 Unique metabolites 1277 728 Unique enzymes 847 939 Unique metabolic reactions 1394 947 Unreachable metabolites 1281/2287 (57%) 75/758 (9.9%) Blocked reactions 728/ 1687 (43%) 140/1102 (13%)

Future developments ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

Conclusion ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

Transporters ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

The Subliminal Toolbox: automating steps in the reconstruction of metabolic networks

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The Subliminal Toolbox: automating steps in the reconstruction of metabolic networks