1. The MGED Ontology Is An Experimental Ontology Bio-Ontologies Aug 8, 2002 Chris Stoeckert, Helen Parkinson and the MGED Ontology Working Group

2. MGED Mission Statement The Microarray Gene Expression Data (MGED) society is an international organization for facilitating the sharing of microarray data from functional genomics and proteomics experiments. MGED was established as a grass roots movement in a meeting in November 1999 in Cambridge, UK Current tasks involve establishing standards for microarray data annotation and representation, facilitating the creation of microarray databases and providing infrastructure for dissemination of experimental and data transformation protocols Long term goals for the future will extend the mission to other functional genomics and proteomics high throughput technologies.

3. http://www.mged.org

4. An Experimental Ontology An ontology for microarray experiments –Not an ontology of life but of experiments –Parts are applicable to describing experiments in general Our approach to interfacing with other ontologies is “experimental” –Not mapping terms from related ontologies –Provide a framework to hang other ontologies off of Know where to find different types of annotation How to interpret that annotation

5. Microarray Information to be Captured Figure from: David J. Duggan et al. (1999) Expression Profiling using cDNA microarrays. Nature Genetics 21: 10-14

6. Flow Chart for Microarray Data

7. Minimal Information About a Microarray Experiment (MIAME) Provides the concepts for the ontology Array design description –Common features of the array as the whole, and the description of each array design elements (e.g., each spot) Gene expression experiment description –Experimental design –Samples used, extract preparation and labeling –Hybridization procedures and parameters –Measurement data and specifications of data processing See Brazma et al Nature Genetics 2001 and http://www.mged.org/Workgroups/MIAME/miame.html

8. MIAME Section on Samples (Biomaterials) Biosource properties –Organism –Contact details for sample –Descriptors relevant to the particular sample, such as Sex Age Developmental stage Organism part (tissue) Cell type Animal/ plant strain or line Genetic variation (e.g., gene knockout, transgenic variation) Individual genetic characteristics (e.g., disease alleles, polymorphisms) Disease state or nornal Is additional clinical information available (link) The individual (for interrelation of the samples in the experiment) Biomaterial manipulations: laboratory protocol, including relevant parameters, e.g., –Growth conditions –In vivo treatments (organism or individual treatments) –In vitro treatments (cell culture conditions) –Treatment type (e.g., small molecule, heat shock, cold shock, food deprivation) –Compound –Separation technique (e.g., none, trimming, microdissection, FACS)

9. MicroArray Gene Expression Object Model (MAGE OM) Provides some specification of concepts Developed to provide an exchange format for microarray data. –Implemented in XML (MAGE-ML)

11. Relationship of MGED Efforts MAGE MIAME DB MIAME DB External Ontologies/CVs MGED Ontology

12. The MGED Ontology Working Group Acts through –a mailing list of over 250 –working group meetings organized at conferences like ISMB and of course MGED Collects resources (dictionaries, controlled vocabularies, ontologies) for terms to describe microarray experiments –Sample (biomaterial) –Experimental conditions (treatments) –Experimental design (study design)

13. The MGED Ontology Home Page http://www.cbil.upenn.edu/Ontology

15. The MGED Ontology Provides a Listing of Resources for Many Species

16. The MGED Ontology Organizes the Resources According to Concepts

17. The MGED Ontology is Structured in DAML+OIL using OILed 3.4

18. MGED Ontology: BiomaterialDescription: BiosourceProperty: Age

19. MGED Ontology: BiosourceOntologyEntry: DiseaseState

20. MGED Ontology: Study

21. MGED Ontology Use Cases Make it easier and more accurate to annotate a microarray experiment. –Build forms that provide menus of terms and links to external resources. See MIAMEexpress! –Only ask for relevant terms and fill in terms that can be inferred. Use structured fields and controlled terms to query databases. –Return a summary of all experiments that use a specified type of biosource. –Return a summary of all experiments done examining effects of a specified treatment ? Aid in experiment design by providing parameters to consider about samples, organization of treatments. ? Use to check if “MIAME-compliant.” –Assess only fields that are relevant –Check for proper use of terms ? Build gene networks based on biomaterial description –Use structured descriptions to cluster, build models, etc.

22. External References ©- BioMaterialDescription © -Biosource Property © -Organism © -Age © -DevelopmentStage © -Sex © -StrainOrLine © -BiosourceProvider © -OrganismPart © -BioMaterialManipulation © -EnvironmentalHistory ©- CultureCondition ©- Temperature ©- Humidity ©- Light © -PathogenTests © -Water © -Nutrients © -Treatment © -CompoundBasedTreatment (Compound) (Treatment_application) (Measurement) MGED Ontology Instances NCBI Taxonomy Mouse Anatomical Dictionary International Committee on Standardized Genetic Nomenclature for Mice International Committee on Standardized Genetic Nomenclature for Mice Mouse Anatomical Dictionary ChemIDplus Mus musculus musculus id: 39442 7 weeks after birth Stage 28 Female C57BL/6N Charles River, Japan Liver 22  2  C 55  5% 12 hours light/dark cycle Specified pathogen free conditions ad libitum MF, Oriental Yeast, Tokyo, Japan Fenofibrate, CAS 49562-28-9 in vivo, oral gavage 100mg/kg body weight An example of microarray sample annotation using the MGED ontology Susanna A. Sansone, Helen Parkinson, Philippe Rocca-Serra, Chris Stoeckert and Alvis Brazma

23. The MGED Ontology in Action: MIAMExpress

24. The MGED Ontology in Action: RAD

25. Summary The MGED Ontology is being developed within the microarray community to provide consistent terminology for experiments. This community effort has resulted in a list of multiple resources for many species. The list is organized by defined concepts and augmented with terms for widely applicable concepts (e.g., “age”, “sex”). The concepts are structured in DAML+OIL and available in other formats (rdfs) The MGED Ontology is a work in progress –More instances (create IDs) –Constraints –Concepts for other parts of microarray experiment

26. http://www.ebi.ac.uk/SOFG