The document introduces libAnnotationSBML, a library for linking annotated SBML models to MIRIAM and related web services. It provides a unified interface to web services like ChEBI, KEGG, and UniProt to retrieve ontology terms and annotations for model components. This allows tools to exploit annotations and simplify tasks like suggesting corrections to models, intelligently generating models, and automating other tedious jobs by programmatically reasoning over annotated models. While dynamic linking of models to databases is still developing, libAnnotationSBML aims to make working with annotations easier.

1. libAnnotationSBML Neil Swainston Manchester Centre for Integrative Systems Biology 29 March 2009

2. Introduction Library ( not a tool ) for linking annotated SBML models to MIRIAM and related web services Writing and reading of annotations Java – could be extended

3. Purpose of annotations Provide definitive , unique identifier for “stuff” One motivation: mapping experimental data to models Need annotated models AND annotated data

4. AnnotationWizard Shameless copy of Falko’s semanticSBML See also SAINT (Allyson) Principle: Iterate through model Submit each species to an appropriate web service search facility ( ChEBI or UniProt ) Prompt user for confirmation Update model with annotation Has also been wrapped as a web service itself

5. Annotating models: yeast Genome-scale SBML model of yeast metabolism All 2153 molecules have MIRIAM annotations

6. Project overview Enzyme kinetics Quantitative metabolomics Quantitative proteomics SBML Model Parameters (K M , K cat ) Variables (metabolite, protein concentrations) PRIDE MeMo SABIO-RK Web service Web service Web service MeMo-RK

7. KineticsWizard

8. Project overview Enzyme kinetics Quantitative metabolomics Quantitative proteomics SBML Model Parameters (K M , K cat ) Variables (metabolite, protein concentrations) PRIDE MeMo SABIO-RK Web service Web service Web service MeMo-RK

9. CellDesigner plugin

10. Purpose of annotations Provide definitive, unique identifier for “stuff” One motivation: mapping experimental data to models Need annotated models AND annotated data “ Tagging” More interesting purpose … Use the annotations to reason over the model

11. Purpose of annotations Easy question Is my model annotated? Simple answer: yes Can be answered solely by libSBML More interesting question Is my model annotated well ? Do my reactions elementally balance? Simple answer may be yes or no, but harder to determine Can’t be determined solely by libSBML

12. Isn’t ChEBI grrrreat … <species id=”glc&quot; name=&quot;D-Glucose&quot;> <annotation> <rdf:li rdf:resource=&quot;urn:miriam:obo.chebi:CHEBI:17634&quot;/> </annotation> </species>

13. libAnnotationSBML: what it does Provides unified interface to following web services : ChEBI KEGG UniProt SBO others… Wraps these calls so that it appears that you are accessing these locally

14. MIRIAM UniProt ChEBI KEGG libAnnotationSBML SBase annotation OntologyTerm(s) Determine ontology Map to web service

15. OntologyTerm Model components can be parsed to return OntologyTerm s OntologyTerms have the following interface: Development of tools to exploit annotations becomes greatly simplified: OntologyTerm[] ots = sbmlUtils.getOntologyTerms( sbase ); OntologyTerm ot = ots[0]; ot.getName(); ot.getSynonyms(); ot.getFormula();

16. Purpose of annotations: to allow automation of tedious jobs D-Glyceraldehyde + NAD+ <=> D-Glycerate + NADH + H+

17. Purpose of annotations: to allow automation of tedious jobs Suggest corrections to existing models Incorrect annotations Missing reactants / products Stoichiometry Better still: intelligent generation of models ? AutoComplete?

18. Wish list Support more web services Write it in C++ WSDLs in MIRIAM??

19. Wish list BUT dynamic linking of models to databases is still a little way off Web services are inconsistent getName()? getDescription()? getTitle()? Semantic web services needed

20. Finally … Hopefully makes doing things with annotations easier Have a look if you’re interested: http://mcisb.sourceforge.net

21. libAnnotationSBML Neil Swainston Manchester Centre for Integrative Systems Biology 29 March 2009