Presentation on theme: "The use of Ontology in Organising and Managing Protein Family Resources Katy Wolstencroft, University Of Manchester."— Presentation transcript:
The use of Ontology in Organising and Managing Protein Family Resources Katy Wolstencroft, University Of Manchester
Overview Research communities working on specific protein families Family Resource – central focus for the community Problems communities tend to be small Difficult to sustain resources for small number of people - funding – community input / consistency
Protein Family Test Cases Protein Phosphatases: Original test family dephosphorylation, involved in control and communication. http://www.bioinf.man.ac.uk/phosphabase ABC Transporters: (GSK Pennsylvania) transport of biological molecules through cells and organelles. Both implicated in human disease
Solutions From Ontology? General biological data problems * Nomenclature and free text data Sustainability Consistency and ambiguity Problems associated with both data extraction and data retrieval
GO Accessible Resources GO – de facto standard – description of gene products Biological Resources – annotating data to GO terms
Domain-specific Ontology GO allows efficient collection of biological data from heterogeneous sources – not rich enough to describe a whole protein family domain How should the information be stored? What information should be stored?
Requirements Protein Phosphatase Inhibitors - protein inhibition, transcriptional repression Activators - protein activation, transcriptional activation Domain Structure Disease Association Genetic Localisation Tissue Expression Enzyme - substrates/ products Cofactor/prosthetic group/molecule required for activation ABC Transporters Inhibitors - protein inhibition, transcriptional repression Activators - protein activation, transcriptional activation Domain Structure Disease Association Genetic Localisation Tissue Expression Transported substrates
System Requirements PhosphaBase PhosphaBase Doamin Ontology DAML+OIL description logic Relational Database – MySql User interface – Java Servlet Free access over the internet MySQL and Java free Java platform independent ABC Transporters ABC Domain Ontology DAML+OIL description logic Relational Database - Oracle User Interface – Ontology driven interface Internal Company Use Limited access
Architecture Advantages /Disadvantages Sustainability – Data capture can be automated. Diagnostics – Classification of unknown proteins. *Major application in annotation of new genomes* Accessibility and Portability – Free availability over the Internet. All software freely available Issues Maintenance – automation and use of ontology reduces human intervention but the ontology needs occasional maintenance Standards – DAML+OIL ontology. Need to migrate to OWL, but OWL does not currently allow qualified number restrictions
Diagnostics Automated Classification Andersen et al (2001) Mol. Cell. Biol. 21 7117-36
Automated Classification DAML+OIL Ontology Domain Architecture rules for group membership
Automated Classification Unknown Sequences Domain Architecture InterProSmart DAML+OIL Ontology Reasoner Domain Architecture rules for group membership Classification
Summary Two rich and useful resources for the phosphatase and ABC transporter research communities A sustainable resource with automatic classification capabilities Generic Model – A robust model could be extended to build similar resources for other protein families in the future Ontology technology – powerful tool in managing biological data
Next Steps Phosphorylation Ontology Control of Phosphorylation mediated by both phosphatases and kinases Collaboration - Protein Kinase Resource (UCSD) to describe whole phosphorylation events Phospho protein Pi phosphatase kinase
Phosphorylation Ontology Goals Use ontology technology to capture whole phosphorylation events Description of phosphorylation events in the cell and the biological pathways they affect Produce phosphorylation resource useful to phosphatase and kinase community and wider.
Acknowledgements Supervisors: Andy Brass, Robert Stevens Advisor and Phosphatase Biologist: Lydia Tabernero GSK: Robin McEntire and the IKM group Funding: Medical Research Council
Interaction Between Resources P and K substrates / inhibitors activators of one another Common Substrates Common inhibitors/ activators Same biological pathways Same diseases PK Substrates Diseases Inhibitors/Activators Biological Pathways
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