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ChEBI and genome scale metabolic reconstructions


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ChEBI and genome scale metabolic reconstructions

  1. 1. ChEBI and genome-scale metabolic reconstructions Neil Swainston Manchester Centre for Integrative Systems Biology 2 nd ChEBI User Group Workshop, EMBL-EBI, Hinxton, UK 23 June 2010
  2. 2. Introduction <ul><li>Genome-scale metabolic reconstructions </li></ul><ul><li>Why ChEBI? </li></ul><ul><li>Kinetic modelling and experimental data </li></ul><ul><li>Conclusions </li></ul>
  3. 3. Genome-scale metabolic reconstructions
  4. 4. Genome-scale metabolic reconstructions <ul><li>Systems biology approach </li></ul><ul><li>Network map of metabolism </li></ul><ul><ul><li>Collection of metabolic reactions </li></ul></ul><ul><li>Computer-readable </li></ul><ul><li>Uses </li></ul><ul><ul><li>Metabolic engineering </li></ul></ul><ul><ul><li>Biological discovery: gene annotation </li></ul></ul><ul><ul><li>Phenotypic behaviour: gene essentiality </li></ul></ul><ul><ul><li>Bacterial evolution </li></ul></ul><ul><ul><li>Knowledge base: computational representation </li></ul></ul>
  5. 5. Systems Biology Markup Language <ul><li>SBML </li></ul><ul><li>Established community standard </li></ul><ul><ul><li>~10 years old </li></ul></ul><ul><ul><li>>500 citations </li></ul></ul><ul><ul><li>>180 software packages </li></ul></ul><ul><li>XML language marking up: </li></ul><ul><ul><li>chemical species (metabolites, enzymes, genes) </li></ul></ul><ul><ul><li>reactions </li></ul></ul><ul><ul><li>compartments </li></ul></ul><ul><ul><li>more… </li></ul></ul>
  6. 6. Systems Biology Markup Language
  7. 7. Limitations <ul><li>What does Cytoplasm , D-glucose , YGL253W mean? </li></ul><ul><ul><li>Same as cyt , glc , Hexokinase 2 ? </li></ul></ul><ul><li>How can we share , compare , merge , parameterise models? </li></ul><ul><ul><li>Some “standard” is required </li></ul></ul><ul><li>Minimal Information Required In the Annotation of Models </li></ul><ul><ul><li>MIRIAM </li></ul></ul>
  8. 8. MIRIAM <ul><li>Standardised format for model annotation </li></ul><ul><ul><li>Subset of Resource Description Framework ( RDF) </li></ul></ul><ul><li>Mapping of model constituent to external data resource </li></ul><ul><li>For metabolites, we use ChEBI: </li></ul><ul><ul><li>D-Glucose is CHEBI:17634 </li></ul></ul>
  9. 9. MIRIAM annotation <species metaid=&quot;id_1&quot; name=&quot;D-Glucose&quot;> <annotation> <rdf:RDF> <rdf:Description rdf:about=&quot;#id_1&quot;> <bqbiol:is> <rdf:Bag> <rdf:li rdf:resource=&quot;urn:miriam:obo.chebi:CHEBI:17634&quot;/> </rdf:Bag> </bqbiol:is> </rdf:Description> </rdf:RDF> </annotation> </species>
  10. 10. For example… <ul><li>Genome-scale SBML model of yeast metabolism </li></ul><ul><li>MIRIAM compliant </li></ul><ul><ul><li>All 2153 molecules have unique database references </li></ul></ul><ul><ul><li>Community standards have been followed </li></ul></ul><ul><ul><li>Should be entirely unambiguous for third party users </li></ul></ul><ul><ul><li>Should be usable in third party tools </li></ul></ul>
  11. 12. Why ChEBI? <ul><li>Could also use KEGG, PubChem, HMDB? </li></ul><ul><ul><li>Occasionally we do… </li></ul></ul><ul><li>Excellent search facility </li></ul><ul><ul><li>Both web and web service </li></ul></ul><ul><li>Web service allows us to develop automation tools </li></ul><ul><ul><li>SBML Annotation Wizard </li></ul></ul>
  12. 13. SBML Annotation Wizard <ul><li>Principle: </li></ul><ul><ul><li>Iterate through model </li></ul></ul><ul><ul><li>Submit each species to an appropriate web service search facility ( ChEBI or UniProt ) </li></ul></ul><ul><ul><li>Search names and synonyms </li></ul></ul><ul><ul><li>Prompt user for confirmation </li></ul></ul><ul><ul><li>Update model with annotation </li></ul></ul>
  13. 14. SBML Annotation Wizard <ul><li>Can also be configured to search with chemical formulae </li></ul><ul><li>Other tools exist with similar functionality </li></ul>
  14. 15. Why ChEBI? <ul><li>Good coverage, but “holes” exist </li></ul><ul><li>Submission tool </li></ul><ul><ul><li>During recent work, molecules have been submitted to ChEBI </li></ul></ul><ul><ul><li>Rapid turn around </li></ul></ul>
  15. 16. Why ChEBI? <ul><li>Fast search facility </li></ul><ul><ul><li>Can be exploited to work “in real time” </li></ul></ul><ul><ul><li>Autofill facility </li></ul></ul><ul><li>Rather than annotate models after generation, use annotation to drive their generation </li></ul><ul><li>SuBliMinaL </li></ul>
  16. 17. SuBliMinaL
  17. 18. Autofill <ul><li>Useful elsewhere </li></ul><ul><ul><li>Used in experimental data metadata collection </li></ul></ul><ul><ul><li>Excel plugin ? </li></ul></ul>
  18. 19. Why ChEBI? <ul><li>Comprehensive web service facility </li></ul><ul><ul><li>Goes beyond names </li></ul></ul><ul><ul><li>Can retrieve pretty much everything from web service that is available through web interface </li></ul></ul>
  19. 21. Reaction balancing <ul><li>Access to charge and formula </li></ul><ul><li>Can automate model checking process </li></ul><ul><ul><li>Correct protonation state </li></ul></ul><ul><ul><li>Correct stoichiometry </li></ul></ul><ul><ul><li>Missing cofactors </li></ul></ul><ul><li>Application written </li></ul><ul><ul><li>Useful (and necessary) for genome-scale reconstructions </li></ul></ul>
  20. 22. Reaction balancing in SuBliMinaL
  21. 23. Interfacing with cheminformatics <ul><li>ChEBI annotations allows us to think of networks cheminformatically as well as mathematically </li></ul><ul><ul><li>Programmatic access to InChI strings </li></ul></ul><ul><ul><li>InChI strings can be computationally interpreted </li></ul></ul><ul><ul><li>Automated network gap filling? </li></ul></ul><ul><ul><li>Similarity searching of “danglers” within network </li></ul></ul>
  22. 24. Kinetic modelling project overview Enzyme kinetics Quantitative metabolomics Quantitative proteomics SBML Model (single pathway) Parameters (K M , k cat ) Variables (metabolite, protein concentrations) PRIDE MeMo SABIO-RK Web service Web service Web service MeMo-RK
  23. 25. Mapping experimental data to models <ul><li>Relatively easy </li></ul><ul><li>Model components and data annotated with same terms </li></ul><ul><ul><li>ChEBI and UniProt </li></ul></ul><ul><li>ChEBI acts as “glue” </li></ul>
  24. 27. Conclusions <ul><li>Metabolic reconstructions (and experimental data) require annotation </li></ul><ul><li>ChEBI provides comprehensive resource for representing metabolites </li></ul><ul><ul><li>Also welcome new submissions </li></ul></ul><ul><li>ChEBI provides excellent web services , allowing the development of automated tools </li></ul><ul><ul><li>Synonyms, charge, formula, InChI string </li></ul></ul><ul><ul><li>Also mass, hierarchical relationships </li></ul></ul>
  25. 28. Thanks…
  26. 29. No Thanks…
  27. 30. Many Thanks…
  28. 31. ChEBI and genome-scale metabolic reconstructions Neil Swainston Manchester Centre for Integrative Systems Biology 2 nd ChEBI User Group Workshop, EMBL-EBI, Hinxton, UK 23 June 2010