1. 1 MAGE: Revised submission against LSR RFP-007 "Gene Expression" Ugis Sarkans, EBI Michael Miller, Rosetta Inpharmatics

2. 2 Overview Acknowledgements Specification history and structure Fundamental Terms UML Packages Mapping from PIM to XML-PSM Schedule Resources

3. 3 Acknowledgements Doug Bassett (Rosetta) Derek Bernhart (Affymetrix) Alvis Brazma (EBI) Steve Chervitz (Affymetrix) Francisco Dela Vega (Applied Biosystems) Michael Dickson (NetGenics) David Frankel (IONA) Ken Griffiths (NetGenics) Scott Markel (NetGenics) Michael Miller (Rosetta) Dave Nellesen (Incyte) Alan Robinson (EBI) Ugis Sarkans (EBI) Barry Schwartz (Affymetrix) Martin Senger (EBI) Paul Spellman (Stanford) Jason Stewart (NCGR) Charles Troup (Agilent) participants of MAGE programming jamboree (hosted by Iobion) in Toronto, September 2001

4. 4 Model -Driven Architecture Platform Independent Model (UML) –most of the effort spent on this Platform Specific Model –XML UML (refined from PIM): –not used (Rational Rose profile for UML not that useful) DTD –generated from PIM –manual modifications

5. 5 History of the submittal lifesci/01-06-02 - an interim draft before the Danvers meeting –not enough time to work out XML lifesci/01-08-01 - not the final submission –programming jamboree after the Toronto meeting helped a lot, especially in the XML mapping area lifesci/01-10-01 - current submission

6. 6 Specification Structure Text document with explanations, including all diagrams –prepared partly by exporting from Rational Rose PIM, UML model as a single XMI file XMI => DTD translation software (as a formal representation of the mapping rules) XML DTD

7. 7 Fundamental Terms BioSample - tissue, cell-line, etc. that may be treated BioMaterial - generic term for biological- based material BioSequence - an abstraction of a biological sequence BioAssay –treatment of an array with a labeled extract, i.e. hybridization –experimental step in a broader sense

8. 8 Fundamental Terms (2) Reporter - the physical representation of biosequence(s) on an array Feature - location on an array Event - description of an action, i.e. treatment of a BioSample or the act of hybridization Transformation - a specific Event, transforming a set of data to another set of data.

9. 9 UML Packages (1) BioSequence and BQS BioMaterial BioEvent ArrayDesign and DesignElement ArrayManufacture BioAssay BioAssayData

10. 10 UML Packages (2) Experiment HigherLevelAnalysis Miscellaneous –Describable –Measurement –QuantitationType –Protocol –Audit and Security

11. 11 BSANEBQS Description Protocol Measurement Audit Treatment Transformation BioEventExperiment ArrayDesign BioMaterial BioAssayData BioAssay DesignElement UML Packages (3) HigherLevelAnalysis BioSequence ArrayManufacture QuantitationType

12. 12 Package dependencies

13. 13 Important package dependencies

14. 14 Experiment Represents the container for a hierarchical grouping of BioAssays ExperimentDesign decribes and annotates the overall design and purpose of the experiment Description of experimental steps can be structured by ExperimentalFactors/ FactorValues: –ExperimentalFactor is a part of ExperimentDesign –FactorValues can be attached to BioAssays

15. 15 Experiment

16. 16 HigherLevelAnalysis The results of performing analysis on the BioAssayData from an Experiment Clustering allows specifying the results of analysis as a hierarchical tree Cluster Nodes can have NodeValues and are associated with *Dimension objects

17. 17 BioAssayData The data associated with either a measured BioAssay or a derived BioAssay Data is conceptually a 3-D matrix, with dimensions: –BioAssayDimension –DesignElementDimension –QuantitationTypeDimension Transformations are used to capture data processing sequence and rules –*Mapping objects formalize dimension translations Two representations for BioDataValues: –a set of BioDataTuples –BioDataCube

18. 18 BioAssayData

19. 19 BioAssayData BioAssay QuantitationType DesignElement Transformation

20. 20 QuantitationType StandardQuantitationTypes and SpecializedQuantitationTypes list of SQTs can refer to a Channel object QuantitationTypeMap - within BioAssayData package

21. 21 BioAssay Three types of BioAssays (experimental steps): –PhysicalBioAssay Contains information and annotation on the event of joining an Array with BioMaterial, typically with LabeledExtract(s); also, Treatments –MeasuredBioAssay FeatureExtraction –DerivedBioAssay corresponds to a dry-lab experimental step

22. 22 BioAssay

23. 23 Array Manufacturing information about the implementation of an array design –Defects and deviations from the design can be recorded FeatureDefects ZoneDefects –The LIMS biomaterial information for what was put on each feature can be recorded here –ArrayGroups and Fiducials

24. 24 Array

25. 25 BioMaterial Describes how a BioSource is treated to obtain the BioMaterial for Hybridization (typically a LabeledExtract) Used by a BioAssayCreation in combination with an Array to produce a PhysicalBioAssay A set of treatments are typically linear in time but can form a Directed Acyclic Graph Formalization of Treatments with Compounds

26. 26 BioMaterial

27. 27 DesignElement DesignElements –Features are the locations on the array –Reporters represents some biological sequence (clone, oligo, etc.) that can be placed on one or more features immobilized characteristics –CompositeSequence is a grouping that represents a biological sequence composed of other biological sequences (gene, exon, etc.) biological characteristics *Maps - for relating Features to Reporters etc –MismatchInformation

28. 28 DesignElement

29. 29 BioSequence BioSequence class - abstraction of various biosequences DatabaseEntries for characterizing BioSequences Simplication of BSANE draft; will need to be compatible with the end result of BSANE

30. 30 ArrayDesign ArrayDesign describes a microarray design that can be manufactured –Zone information –DesignElementGroups

31. 31 ArrayDesign

32. 32 BioEvent Abstraction of various MAGE events: –physical (e.g., BioMaterial Treatment) –data manipulation (Transformation) Have associated ProtocolApplications (an ordered list) Subclasses have some target (the result of the BioEvent) Often have sources Relevant for BioMaterial, BioAssay, BioAssayData packages

33. 33 Protocol Protocol and ProtocolApplication –Protocol describes a generic laboratory procedure or analysis algorithm –ProtocolApplication describes the actual application of a protocol –ProtocolApplication: values for the replaceable parameters any variation from the Protocol Similarly: –Hardware and HardwareApplication –Software and SoftwareApplication

34. 34 Protocol

35. 35 Miscellaneous (1) Hierarchy of top-level abstract classes –Extendable - can have properties –Describable - can have also Descriptions and Security and Audit information –Identifiable - also has (unambiguous within some scope) identifier and a name AuditAndSecurity package –Contact/Person/Organization classes –tracking of changes (audit trail) –user security (access rights to MAGE objects)

36. 36 Miscellaneous (2) Description package –Description is a container for free text description OntologyEntries DatabaseEntries BibliographicReferences BQS package –BibliographicReference class Measurement package –Measurement is a quantity with a unit –simple Measurement ontology provided

37. 37 DTD & XML Format …... >... * slide borrowed from Angel Pizarro, UPenn

38. 38 XML tree example AuditAndSecurity_pkg Contact_assnlist ExperimentDesign_assn Experiment_pkg Experiment_assnlist Experiment Contact_ref ExperimentDesign Provider_assnref MAGE-ML Contact * slide borrowed from Angel Pizarro, UPenn

39. 39 Programming APIs Mapping of OM to language-specific OMs API’s are automatically generated from the OM specifications –Get/set methods for associations –Get/set methods for attributes XML language-specific OM marshallers/unmarshallers - also automatically generated

40. 40 Programming APIs (cont.) Use standard modules/packages –Xerces, JDK, etc. Implementation in Java, C++, Perl Building annotation tools/database access modules on top of these APIs

41. 41 Schedule LSR ‘vote to vote’ at Dublin OMG meeting in November –LSR, AB, DTC votes at Dublin OMG meeting Setting up FTF open source implementation efforts –Jamboree II at EBI, December 6-11 MAGE v.2.0 –current MAGE MAGE v.2.0 mapping rules

42. 42 Web Sites MAGE specification - hosted by Rosetta –links to documents presentations UML models –XMI files –Rose.mdl files –HTML version –PNG image files of diagrams –http://www.geml.org/omg.htm MGED programming effort: –http://sourceforge.net/projects/mged

43. 43 Mailing Lists Specification-related –lsr-ge@ebi.ac.uk –to subscribe, send the following to majordomo@ebi.ac.uk subscribe lsr-ge MAGE-STK development-related –https://lists.sourceforge.net/lists/listinfo/mged- mage

44. 44 Questions?