1. The MGED Ontology Workshop MGED 7 September 8, 2004 Chris Stoeckert Center for Bioinformatics & Dept. of Genetics University of Pennsylvania

2. MGED Ontology Workshop Agenda What is the MGED Ontology (MO)? What is the MGED Ontology (MO)? Building MO: the process Building MO: the process Using MO Using MO Future development of MO Future development of MO Joe White (TIGR): MO applications from MAGE Jamboree Joe White (TIGR): MO applications from MAGE Jamboree

3. MGED Standardization Efforts MIAME MIAME The formulation of the minimum information about a microarray experiment required to interpret and verify the results. (Brazma et al. Nature Genetics 2001) The formulation of the minimum information about a microarray experiment required to interpret and verify the results. (Brazma et al. Nature Genetics 2001) MAGE-OM MAGE-OM The establishment of a data exchange format and object model for microarray experiments. (Spellman et al. Genome Biol. 2002) The establishment of a data exchange format and object model for microarray experiments. (Spellman et al. Genome Biol. 2002) MGED Ontology MGED Ontology The development of an ontology for microarray experiment description and biological material (biomaterial) annotation in particular. (Stoeckrt & Parkinson, Comp. Funct. Genom. 2003) The development of an ontology for microarray experiment description and biological material (biomaterial) annotation in particular. (Stoeckrt & Parkinson, Comp. Funct. Genom. 2003) Transformations Transformations The development of recommendations regarding microarray data transformations and normalization methods. The development of recommendations regarding microarray data transformations and normalization methods. RSBI RSBI Reporting Structure for Biological Investigations (toxicogenomics, environmental genomics, metabol/nomics) Reporting Structure for Biological Investigations (toxicogenomics, environmental genomics, metabol/nomics)

4. MGED Ontology (MO) Purpose Purpose Provide standard terms for the annotation of microarray experiments Provide standard terms for the annotation of microarray experiments Not to model biology but to provide descriptors for experiment components Not to model biology but to provide descriptors for experiment components Benefits Benefits Unambiguous description of how the experiment was performed Unambiguous description of how the experiment was performed Structured queries can be generated Structured queries can be generated Ontology concepts derived from the MIAME guidelines/MAGE-OM Ontology concepts derived from the MIAME guidelines/MAGE-OM Also incorporating concepts from Transformations and RSBI Also incorporating concepts from Transformations and RSBI

5. Relationship of MO to MAGE-OM MO class hierarchy follows that of MAGE-OM MO class hierarchy follows that of MAGE-OM Association to OntologyEntry Association to OntologyEntry MO provides terms for these associations by: MO provides terms for these associations by: Instances internal to MO Instances internal to MO Instances from external ontologies Instances from external ontologies Take advantage of existing ontologies Take advantage of existing ontologies

6. MGED Ontology Class Hierarchy MGED CoreOntology Coordinated development with MAGE-OM Ease of locating appropriate class to select terms from MGED ExtendedOntology Classes for additional terms as the usage of genomics technologies expand

7. MAGE and MO

9. Main focus of MGED Ontology Structured and rich description of BioMaterials BioMaterial OntologyEntry +characteristics +associations

12. MO and References to External Ontologies

13. MO and references to External Ontologies

14. http://www.sofg.org

15. Standards and Ontologies for Functional Genomics 2 October 23-26, 2004 held at the University of Pennsylvania Medical School www.jax.org/courses/events Funded in part by NHGRI NCRR NERC GSK Co-Hosted by The Jackson Laboratory University of Pennsylvania European Bioinformatics Institute ------------------------ Student Scholarships Available -------------------------------------------------------- Photo by R. Kennedy, B Trist, R. Tarver, for GPTMC

16. http://mged.sourceforge.net/ontologies/index.php

17. Use MGED Ontology for Structured Descriptions (MAGE- ML)

18. MGED Ontology development http://mged.sourceforge.net/ontologies/MGEDontology.p hp OILed OILed File formats File formats DAML file DAML file HTML file HTML file NCI DTS Browser NCI DTS Browser Changes Changes Notes Notes Term Tracker Term Tracker

19. MGED Ontology Working Group Virtual Ontology Workshops Virtual Ontology Workshops Chris Stoeckert, Trish Whetzel (Penn) Chris Stoeckert, Trish Whetzel (Penn) Helen Parkinson, Susanna Sansone (EBI) Helen Parkinson, Susanna Sansone (EBI) Joe White (TIGR) Joe White (TIGR) Gilberto Fragoso, Liju Fan, Mervi Heiskanen (NCI) Gilberto Fragoso, Liju Fan, Mervi Heiskanen (NCI) Helen Causton, Laurence Game (ICL) Helen Causton, Laurence Game (ICL) Chris Taylor (PSI, EBI) Chris Taylor (PSI, EBI) Mged-ontologies mailing list Mged-ontologies mailing list

20. Desirable Microarray Queries Return all experiments with species X examined at developmental stage Y Return all experiments with species X examined at developmental stage Y Sort by platform type Sort by platform type Which are untreated? Treated? Which are untreated? Treated? Treated with what compound? Treated with what compound? How comparable are these? How comparable are these? What can these experiments tell me? What can these experiments tell me?

21. MO and Structured Queries

22. RAD: RNA Abundance Database http://www.cbil.upenn.edu/RAD http://www.cbil.upenn.edu/RAD RAD is part of GUS (Genomics Unified Schema) The GUS platform maximizes the utility of stored data by warehousing them in a schema that integrates the genome, transcriptome, gene regulation and networks, ontologies and controlled vocabularies, gene expression Relational schema (implemented in Oracle) Stores data from gene expression arrays and SAGE Comes with a suite of web-annotation forms (Study- Annotator) MAGE-RAD Translator (MR_T) generates MAGE-ML files for exports Manduchi et al. 2004 Bioinformatics 20:452-459.

23. RAD Study-Annotator Covers all relevant parts of the MIAME checklist Exploits the MGED Ontology Allows entering of very specific details of an experiment Web-based forms: Modular structure Written in PHP Front-end data integrity checks using JavaScript Manages Data Privacy based on Project/Group selections present in GUS schema Available at http://www.cbil.upenn.edu/RAD/RAD- installation.htm

24. BioMaterial Annotation: Conceptual View

25. RAD Study Annotator: BioMaterial Module

26. RAD Study Annotator: BioSource Form

27. Other Sites Using MO See posters for more details on these!

28. Future Development of MO Areas of Development Areas of Development Ongoing maintenance Ongoing maintenance Ontology language Ontology language Non-array technologies Non-array technologies Biological domain extensions Biological domain extensions MO v2. development MO v2. development

29. Proposed methods for MO development Ongoing maintenance Ongoing maintenance Addition of new instance terms to existing classes Addition of new instance terms to existing classes Fixing typographical errors Fixing typographical errors Adding missing associations Adding missing associations These represent minor changes that should largely not affect software applications that are based on the MO These represent minor changes that should largely not affect software applications that are based on the MO

30. Proposed methods for MO development Ontology language Ontology language Planned changes in the primary language format (from DAML to OWL). Planned changes in the primary language format (from DAML to OWL). Planned changes in the primary ontology editing tool (from OILed to Protégé). Planned changes in the primary ontology editing tool (from OILed to Protégé). These should represent fairly minor differences as far as applications based on the MO are concerned. These should represent fairly minor differences as far as applications based on the MO are concerned. Some minor name changes will be needed to adjust for differences in allowed characters. Some minor name changes will be needed to adjust for differences in allowed characters. New functionalities such as the availability of synonyms may be used to enrich the MO further. New functionalities such as the availability of synonyms may be used to enrich the MO further.

31. Proposed methods for MO development Non-array technologies Non-array technologies Standards efforts for proteomics (PSI) and metabol/nomics (SMRS) would like to add terms for their specific needs. Standards efforts for proteomics (PSI) and metabol/nomics (SMRS) would like to add terms for their specific needs. Classes that are needed for new technologies can be placed under the MGEDExtendedOntology and linked to MGEDCoreOntology classes through properties Classes that are needed for new technologies can be placed under the MGEDExtendedOntology and linked to MGEDCoreOntology classes through properties (i.e., MGEDExtendedOntologyClass has_property (MGEDCoreOntologyClass). (i.e., MGEDExtendedOntologyClass has_property (MGEDCoreOntologyClass). Such development would not impact the MGEDCoreOntology and therefore allow addition of non-array technology classes Such development would not impact the MGEDCoreOntology and therefore allow addition of non-array technology classes Instances that are needed for new technologies may be most appropriate for existing classes in the MGEDCoreOntology Instances that are needed for new technologies may be most appropriate for existing classes in the MGEDCoreOntology The policy for adding and defining instances regarding technology- related terms is to provide a generic name and definition but to supply technology-specific examples (in the definition). The policy for adding and defining instances regarding technology- related terms is to provide a generic name and definition but to supply technology-specific examples (in the definition).

32. A Functional Genomics View Courtesy of Andy Jones

33. Proposed methods for MO development Biological domain extensions Biological domain extensions Areas (e.g., toxicogenomics) where the current specification of Experiment and Biomaterial is not sufficient to fully capture descriptions of experiments Areas (e.g., toxicogenomics) where the current specification of Experiment and Biomaterial is not sufficient to fully capture descriptions of experiments Extensions should fit within the MAGE-OM v1.1 and so ultimately could go into the MGEDCoreOntology. Extensions should fit within the MAGE-OM v1.1 and so ultimately could go into the MGEDCoreOntology. However, as the new classes, subclasses, properties, and instances are under development (and therefore not stable), they should be placed in the MGEDExtendedOntology until mature enough to be migrated over to the MGEDCoreOntology. However, as the new classes, subclasses, properties, and instances are under development (and therefore not stable), they should be placed in the MGEDExtendedOntology until mature enough to be migrated over to the MGEDCoreOntology. The MGED Reporting Structure for Biological Investigations (RSBI)Working Group representing biological domain extensions in toxicogenomics, environmental genomics, and nutrigenomics will take this approach. The MGED Reporting Structure for Biological Investigations (RSBI)Working Group representing biological domain extensions in toxicogenomics, environmental genomics, and nutrigenomics will take this approach. Hear more about this from Jennifer Fostel next! Hear more about this from Jennifer Fostel next!

34. Proposed methods for MO development MO v2 development MO v2 development Reflect the reorganization planned for the MAGE- OM and its new major version (v2). Reflect the reorganization planned for the MAGE- OM and its new major version (v2). MAGE v2 will have major structural changes from MAGE v1.1 and is likely to require major changes in the MO. MAGE v2 will have major structural changes from MAGE v1.1 and is likely to require major changes in the MO. With a MO v2 developed in parallel this should not conflict with the stated plans of the MO to be consistent with MAGE as it will be tied to the new version. With a MO v2 developed in parallel this should not conflict with the stated plans of the MO to be consistent with MAGE as it will be tied to the new version.

35. A Functional Genomics Object Model (FGE-OM) Separate out common components from technology-specific ones Separate out common components from technology-specific ones Allow new domains to be added as new modules to the model Allow new domains to be added as new modules to the model Incorporate ideas from SysBio-OM (Xirasgur et al. Bioinformatics in press) Incorporate ideas from SysBio-OM (Xirasgur et al. Bioinformatics in press) Jones et al. Bioinformatics 2004

36. Proposed Development of MGED Ontology MO 1.x MO 2.x Sept. 2004 Jan. 2005 March 2005 Sept. 2005 Move to OWL/Protege Proteomics in ExtendedOntology RSBI in ExtendedOntology RSBI in CoreOntology