Annotation of SBML Models Through Rule-Based Semantic IntegrationBio-Ontologies SIG, ISMB 200928 June 2009Allyson Lister, Phillip Lord, Matthew Pocock, Anil WipatCISBAN and Newcastle Universityhttp://www.cisban.ac.uk/RBMhelpdesk@cisban.ac.ukPresentation slides covered under the CC-BY-SA 2.5

Telomeres and AgeingImage: Public Domain, NASA, from http://commons.wikimedia.org/wiki/File:Telomere_caps.gif

Checkpoint response to telomere uncapping in budding yeastProctor et al. [1]Image and Model: [1]

What is SBML?Standard formatWidely used (100+ tools)Represents the mathematical modelEnables linking to the underlying biology

Standard format

Widely used (100+ tools)

Represents the mathematical model

Enables linking to the underlying biology

Model Annotation Life CycleGet dataRead literature(Re)build modelParameterise Examine resultsRun and test model

Challenges in Model AnnotationKnowledge in lots of placesHard for a single modeller to retrieve all available knowledgeMost existing data integration tools are not suitable for modellers’ needsMany integration methods are purely syntactic

Knowledge in lots of places

Hard for a single modeller to retrieve all available knowledge

Most existing data integration tools are not suitable for modellers’ needs

Many integration methods are purely syntactic

Rule-Based MediationA core ontology, which is a semantically-rich description of the research domain of interestA set of source ontologies, which are syntactic translations of data formats into OWLResolution of syntactic and semantic heterogeneity occurs separatelyCan use existing, independent ontologies

A core ontology, which is a semantically-rich description of the research domain of interest

A set of source ontologies, which are syntactic translations of data formats into OWL

Resolution of syntactic and semantic heterogeneity occurs separately

Can use existing, independent ontologies

Where is the knowledge?Input data sources: UniProtKB, BioGRID, Pathway CommonsData can end up in SBML format via MFO [2]

Input data sources: UniProtKB, BioGRID, Pathway Commons

Data can end up in SBML format via MFO [2]

How are the data sources integrated?XMLOWLUniprotKBXMLOWLInstancesMFOBioGRIDTelomereOntologyOWLPathwayCommonsResolvesyntacticheterogeneityResolvesemanticheterogeneityRetrievedataExporttoSBMLReviews of integration types [3-6] Reviews for ontology mapping [7-11]

Achieving the XML to OWL ConversionThe XMLTab plugin for Protégé quickly creates classes and instances from XMLProvides syntactic transformation of dataBut, not multiple XML filesMay not be in active development

The XMLTab plugin for Protégé quickly creates classes and instances from XML

Provides syntactic transformation of data

But, not multiple XML files

May not be in active development

Syntactic Ontologies ->Telomere OntologyRules written in SWRLQueries over the telomere ontology are written in SQWRLSWRLTab and Jess are used to run these rules and queriesWhile writing rules/queries is mainly manual, running them is automaticSemantic value is added to the information by mapping it to a semantically-rich core ontology

Rules written in SWRL

Queries over the telomere ontology are written in SQWRL

SWRLTab and Jess are used to run these rules and queries

While writing rules/queries is mainly manual, running them is automatic

Semantic value is added to the information by mapping it to a semantically-rich core ontology

Mappings from UniProtKBupkb:locationSlot(?s, ?l) ˄upkb:Text(?l, ?value) ˄swrlb:equal(?value, “Nucleus”) ->tuo:Nucleus(?l)

What is RAD9?Tell me about something called ‘rad9’Results could be added back to the existing modelCross-referencesSBO annotationsCompartment localisationsRecommended nameThese results allow the addition of information required by the MIRIAM guidelines

Tell me about something called ‘rad9’

Results could be added back to the existing model

Cross-references

SBO annotations

Compartment localisations

Recommended name

These results allow the addition of information required by the MIRIAM guidelines

What interacts with RAD9?In Proctor et al., there are four interacting partners with RAD9Two were identified within the model, and were found by querying the telomere ontologyOf the unknown partners, one was provisionally identified as MEC1.

In Proctor et al., there are four interacting partners with RAD9

Two were identified within the model, and were found by querying the telomere ontology

Of the unknown partners, one was provisionally identified as MEC1.

SummarySBML models require large amounts of data to be mathematically and biologically completeA two-step integration “rule-based mediation” helps model annotationOff-the-shelf technology was used Eases the task of fulfilling MIRIAM guidelinesSWRL rules were used to populate our semantically-rich telomere ontologySQWRL was used for queryingWe found new knowledge that the modeller was not aware of

SBML models require large amounts of data to be mathematically and biologically complete

A two-step integration “rule-based mediation” helps model annotation

Off-the-shelf technology was used

Eases the task of fulfilling MIRIAM guidelines

SWRL rules were used to populate our semantically-rich telomere ontology

SQWRL was used for querying

We found new knowledge that the modeller was not aware of

http://www.cisban.ac.uk/RBMPhillip Lord, Matthew Pocock, Anil Wipat Carole Proctor (10.1098/rsif.2006.0148) Tom Kirkwood Reviewers and conference organisersFunding for CISBAN provided by BBSRC/EPSRC grant ref BB/C008200/1‏

Phillip Lord, Matthew Pocock, Anil Wipat

Carole Proctor (10.1098/rsif.2006.0148)

Tom Kirkwood

Reviewers and conference organisers

Thank you!xkcd.comFunding for CISBAN provided by BBSRC/EPSRC grant ref BB/C008200/1‏

ReferencesCJ Proctor, DA Lydall, RJ Boys, et al. Modelling the checkpoint response to telomere uncapping in budding yeast. Journal of The Royal Society Interface, Vol. 4, No. 12. (22 February 2007), pp. 73-90. AL Lister, M Pocock, A Wipat, Integration of constraints documented in SBML, SBO, and the SBML Manual facilitates validation of biological models. Journal of Integrative Bioinformatics, Vol. 4, No. 3. (2007), 80.Stephan Philippi and Jacob Kohler. Addressing the problems with life-science databases for traditional uses and systems biology. Nature Reviews Genetics, 7(6):482–488, May 2006W. Sujansky. Heterogeneous database integration in biomedicine. J Biomed Inform, 34(4):285–298, August 2001.Lincoln D Stein. Integrating biological databases. Nat Rev Genet, 4(5):337–345, May 2003.R. Alonso-Calvo et al. An agent- and ontology-based system for integrating public gene, protein, and disease databases. J Biomed Inform, 40(1):17–29, February 2007.

ReferencesMarie C. Rousset and Chantal Reynaud. Knowledge representation for information integration. Inf. Syst., 29(1):3–22, 2004.Li Xu and David W. Embley. Combining the Best of Global-as-View and Local-as-View for Data Integration. In Anatoly E. Doroshenko, Terry A. Halpin, Stephen W. Liddle, Heinrich C. Mayr, Anatoly E. Doroshenko, Terry A. Halpin, Stephen W. Liddle, and Heinrich C. Mayr, editors, ISTA, volume 48 of LNI, pages 123–136. GI, 2004.Natalya F. Noy and Mark A. Musen. The PROMPT suite: interactive tools for ontology merging and mapping. Int. J. Hum.-Comput. Stud., 59(6):983–1024, December 2003.HolgerWache et al. Ontology-based integration of information — a survey of existing approaches. In H. Stuckenschmidt, editor, Proceedings of the IJCAI’01 Workshop on Ontologies and Information Sharing, Seattle, Washington, USA, Aug 4-5, pages 108–117, 2001.JinguangGu, BaowenXu, and Xinmeng Chen. An XML query rewriting mechanism with multiple ontologies integration based on complex semantic mapping. Information Fusion, 9(4):512–522, October 2008.

Small PrintThis presentation is covered under the CC-BY-SA 2.5 (http://creativecommons.org/licenses/by-sa/2.5/ ) license and can be found on slideshareat: http://www.slideshare.net/allysonlister/annotation-of-sbml-models-through-rulebased-semantic-integrationThe ontologies created by the authors are covered under the CC-BY 3.0 license, and external ontologies are governed under their own licensing requirements (specifically, SBO, which is covered under the Artistic License as defined on its SourceForge project site at http://sourceforge.net/projects/sbo/).

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