1. LexBIG, EVS and NCBO Browser Publish, Query, & Browse Vocabularies in caBIG January 2008

2. Agenda Overview LexGrid/LexBIG infrastructure Distributed LexBIG API EVS Services BioPortal Browser Next Steps LexBIG Grid Services

3. Team Members Mayo Scott Bauer James Buntrock Sridhar Dwarkanath Thomas Johnson Pradip Kanjamala Jason Leisch Jyoti Pathak Kevin Peterson Craig Stancl Traci St. Martin Coordination & Mentorship Brian Davis Bob Freimuth Tahsin Kurc Joshua Phillips EVS team Johnita Beasley Gilberto Fragoso Frank Hartel Steven Hunter Wilberto Garcia Charles Griffin Jason Lucas Kim Ong John Park Tracy Safran Rob Wynne

4. Grid Services NCI/NCBO Services LexBIG Java API Conceptual Overview LexGrid Model & Storage Browsers and Applications

5. Conceptual Overview LexGrid Model & Storage

6. LexGrid Model & Storage Coding Scheme Relations Concepts Properties Associations describable codingScheme concepts::concepts describable relations::relations describable relations::association relations:: associationInstance associatableElement relations::associationTarget versionableAndDescribable concepts::codedEntry concepts::property concepts::comment concepts::definition concepts::presentation 0..1+concepts0..* +relations 1..* +association 0..*+sourceConcept 0..*+targetConcept 1..*+concept 0..* +property T005: Virus T047: Disease or Syndrome T005 -> causes -> T047

7. Coverage Lexical Semantics (e.g. names, ids, definitions, comments) Logical Semantics (e.g. associations, qualifiers) Context (e.g. language, source) Supports Load and Representation of … Web Ontology Language (OWL) Open Biomedical Ontologies (OBO) UMLS Rich Release Format (RRF) Protégé Frames (various, requires custom loader for each unique flavor) XML & Text (various, requires custom loader for each unique flavor) Available Renderings of the Model XML Schema (master) Formal (XMI, UML) Data Storage/Schema (e.g. RDB, LDAP) Technology-specific (e.g. Castor, EMF) LexGrid Model & Storage

8. LexBIG Java API Conceptual Overview LexGrid Model & Storage

9. Other OBO Content Export Import OWL XML OBO Text Protégé RRF XML Representation LexGrid Vocabulary Model Data Repository LexBIG - API Tools And Services Access Programming Interfaces APIs LexBIG … CTS Apps Java Embed Web Services Distributed LexBIG API Application Server Each LexGrid ‘Node’ provides the software, metadata, indexes, and backing data store to service one or more vocabularies. Each LexBIG Installation represents one LexGrid Node and Java API to administer and query data. File System: Metadata & Indexes

10. LexBIG - API API coverage Administrative FunctionsAdministrative Functions Query Available Code Systems and MetadataQuery Available Code Systems and Metadata Query Concepts, Concept Properties, and QualificationsQuery Concepts, Concept Properties, and Qualifications Query Concept Relationships and QualificationsQuery Concept Relationships and Qualifications API characteristics Conscious separation of service and data classesConscious separation of service and data classes Deferred query resolutionDeferred query resolution Payload optimizationPayload optimization Support of iteratorsSupport of iterators Defined extension points (loaders, exporters, sort algorithms, match algorithms, convenience methods)Defined extension points (loaders, exporters, sort algorithms, match algorithms, convenience methods)

11. LexBIG – API Example Prerequisites ICD-9-CM loaded from UMLS distribution (RRF source files) Target a code system Define a concept ‘space’ (a codedNodeSet) for ICD-9-CM, version 2007 Initially unrestricted and unresolved Restrict the space based by adding constraints Property ‘Semantic Type’ -> exact match -> “Disease or Syndrome” Primary text match -> sounds like -> ‘infeksion’ Any text stemmed match -> ‘classify’ (to match ‘classified’, ‘classifying’, etc) Must contain a property with name -> ‘UMLS_CUI’ Concept must be active Indicate sort preferences and limit number returned Sort by code, ascending Limit to top 5 Resolve!

12. LexBIG – API Example OK, now find some relationships… Target a code system Define an unrestricted graph for a target ontology (e.g. ICD-9-CM) Restrict by adding constraints Restrict to parent/child relationships (UMLS-defined ‘PAR’ = has parent) Restrict to the codedNodeSet defined in the previous example Indicate extent of navigation Maximum 2 levels, moving in forward direction Maximum 50 nodes resolved overall Resolve!

13. Example of Work in Progress for Mar 2008 release… Feature Request: Provide a more convenient way to query hierarchies with different underlying hierarchical names and structures. Solution: Register additional Metadata indicating supported hierarchical relationships, root nodes, and direction of navigation to traverse from parent to child. Provide relation-independent and direction-agnostic convenience methods to allow tree building without need to know specific behavior of each ontology. LexBIG – API R1 C1 C2 hasSubtype R1 C1 C2 ‘CHD’ R1 C2 C5 isa C4 C3 developsFrom

14. Solution: Register additional Metadata indicating supported hierarchical relationships, root nodes, and direction of navigation to traverse from parent to child. Provide relation-independent and direction-agnostic convenience methods to allow tree building without need to know specific behavior of each ontology. supportedHierarchy #1 Hierarchy ID = is_a Root = R1 Association = hasSubtype ForwardNavigable = true New Convenience Methods… Resolving root of the is_a type hierarchy is always ‘R1’ Resolving first level of tree always provides ‘C2’ & ‘C3’ Etc… LexBIG – API supportedHierarchy #2 Hierarchy ID = is_a Root = R1 Association = CHD ForwardNavigable = true supportedHierarchy #3 Hierarchy ID = is_a Root = R1 Association = isa, develops_from ForwardNavigable = false

15. EVS caCORE APIs LexBIG Java API Conceptual Overview LexGrid Model & Storage

16. EVS caCORE API - Distributed LexBIG Database Server LexBIG in Local JVM LexBIG Install LexBIG Distributed API Client in Local JVM LexBIG API Proxy caCORE EVS Server Spring Remoting Database Server LexBIG Install JDBC Direct Invocation Distributed API

17. Query-by-example (QBE) system EVS 3.2 model Java Web Services REST (HTTP / XML) caCORE EVS Server Web Services XML / HTML Java QBE LexBIG Install DAO Cache Service Layer Database Server JDBC EVS caCORE API – QBE

18. Grid Services EVS caCORE APIs LexBIG Java API Conceptual Overview LexGrid Model & Storage

19. Grid Services – EVS 3.1 Data Model The EVS Grid Service is accessible via the caGRID Portal: http://cagrid-portal.nci.nih.govhttp://cagrid-portal.nci.nih.gov The following is a list of the available operations via EVS Grid Service. Operation NameDescription ========================= getHistoryRecordsSearches a valid vocabulary in NCI thesaurus for history information. searchSourceByCodeSearches the Meta Thesaurus based on Source code. searchMetaThesaurusSearches NCI meta thesaurus and returns Meta Thesaurus information that meet the search criteria. getMetaSourcesReturns all Metathesaurus Sources contained in the EVS. searchDescLogicConceptSearches a valid Vocabulary such as NCI Thesaurus and returns Description Logic concepts that meet the search criteria. getServiceSecurityMetadataReturns the service's security metadata. getVocabularyNamesReturns all the vocabularies present in the Description Logic in caCORE 3.1 EVS service. Next slide is a screen shot of the EVSGridService information viewable from the caGRID Portal. The next release of caCORE/EVS 4 will support the full EVS 3.2 model n the Grid

21. LexBIG Installation caGrid Node hosting Service Client Client Invokes caGrid Service caGrid Service uses Distributed LexBIG to implement call Distributed LexBIG returns requested information to caGrid Service returns response to client Grid Services – LexBIG Prototype

22. LexBIG Model in Introduce … The LexBIG Model is loaded into The Introduce Grid Service Authoring Toolkit via XSD files. Grid Services – LexBIG Prototype

23. Using the LexBIG Model in a caGrid Service Services can then be defined using the imported types. LexBIG Model types loaded from XSDs Defining Services ‘CodingSchemeRenderingList’ is used as the output of caGrid Service ‘getSupportedCodingSchemes()’ Grid Services – LexBIG Prototype

24. Sample caGrid Service call ‘getSupportedCodingSchemes()’ ClientcaGrid ServiceDistributed LexBIG Calls caGrid ‘getSupportedCodingSchemes()’ Calls Distributed LexBIG ‘getSupportedCodingSchemes() Returns result of call to caGrid Service Results are returned to client with all appropriate caGrid security mechanisms Grid Services – LexBIG Prototype

25. Creating a caGrid Service Model Definitions (XSDs) XSD files are imported into the Introduce Toolkit getSupportedCodingSchemes() getSortAlgorithm(String) … Methods are created in Introduce using the imported model definitions as input/output parameters

26. Creating a caGrid Service With the model loaded and methods created, the service can then be deployed to a caGrid Node. caGrid Node Introduce Toolkit Output: A deployed service to the Grid, plus client software to access the service.

27. Grid Services EVS caCORE APIs LexBIG Java API Conceptual Overview LexGrid Model & Storage Browsers and Applications

28. LexBIG GUI

29. Gene Ontology HL7 Medical Dictionary for Regulatory Activities Terminology (MedDRA) National Drug File - Reference Terminology NCI MetaThesaurus NCI Thesaurus SNOMED Clinical Terms The MGED Ontology UMLS Semantic Network Zebrafish Stand-alone terminologies BioCarta Terms Derived from online maps of molecular relationships, adapted for NCI use, 0601C Clinical Bioinformatics Ontology, June 2005 Canonical Clinical Problem Statement System, 1999 Clinical Classifications Software, 2003 Clinical Data Interchange Standards Consortium, 0601C COSTAR, 1989-1995 CRISP Thesaurus, 2004 Common Terminology Criteria for Adverse Events, 2003 Cancer Therapy Evaluation Program (CTEP), 2004 DSM-IV, 1994 NCI Developmental Therapeutics Program, 0601C Expression Library Classification Food and Drug Administration, 0601C Gene Ontology, 2004_03_02 Healthcare Common Procedure Coding System, 2005 Home Health Care Classification, 2003 Health Level Seven Vocabulary, 1998-2002 ICPC2E-ICD10 relationships from Dr. Henk Lamberts, 1998 HUGO Gene Nomenclature, 2004_04 ICD10, 1998 ICD-9-CM, 2005 International Classification of Diseases for Oncology (ICD) ICPC2 - ICD10 Thesaurus, 200403 International Classification of Primary Care, 1993 Online Congenital Multiple Anomaly/Mental Retardation Syndromes, 1999 NCI Mouse Terminology, 0601C KEGG Pathway Database, 0601C LOINC 2.13 MEDLINE (1995-1999) McMaster University Epidemiology Terms, 1992 Mitelman Database of Chromosome Aberrations in Cancer (MDBCAC), 2005_12 MedDRA, 6.0 MEDLINE (2000-2005) MedlinePlus Health Topics_2004_08_14, 20040814 Online Mendelian Inheritance in Man, 1993 Multum MediSource Lexicon, 2004_03 Medical Subject Headings, MSH2005_2004_10_12 UMLS Metathesaurus Metathesaurus FDA National Drug Code Directory, 2004_01 Metathesaurus additional entry terms for ICD-9-CM, 2005, 2005 ICPC2 - ICD10 Thesaurus, 7-bit Equivalents, 0403 ICPC2 - ICD10 Thesaurus, American English Equivalents, 0403 Metathesaurus Version of Minimal Standard Terminology Digestive Endoscopy, 2001 Metathesaurus forms of SNOMED Clinical Terms, 2004_01_31 NCBI Taxonomy, 2004_09_30 NCI modified Common Terminology Criteria for Adverse Events v3.0, 2003 NCI-GLOSS (Cancer.gov Dictionary), 0601C National Cancer Institute Thesaurus, 2006_01C NCI Metathesaurus NCI SEER ICD Neoplasm Code Mappings, 1999 National Drug File - Reference Terminology, 2004_01 National Library of Medicine Medline Data Omaha System, 1994 Physician Data Query, 2005_12 Portfolio Management Application (PMA), 2003 Quick Medical Reference (QMR), 1996 QMR clinically related terms from Randolph A. Miller, 1999 RXNORM Project, META2005AA Cumulative Update 2004_11_17, 2005AA SNOMEDCT Clinical Terms, 2004_01_31 Standard Product Nomenclature, 2003 Metathesaurus Source Terminology Names UMDNS: product category thesaurus, 2005 University of Washington Digital Anatomist, 1.7.3 Individual Terminologies Metathesaurus terminologies

30. NCI BioPortal

31. http://bioportal.nci.nih.gov/ncbo/faces/index.xhtml Encourage use and feedback Notes … General query, navigation, and visualization in place Some operations not performing well and under investigation Suspect bottlenecks in Distributed LexBIG API layer; compared with NCBO implementation which works directly against the LexBIG Java API.

32. Future Browser Support Invitation for Participation !!! NCI- Terminology Open Portal (TOP) Project https://gforge.nci.nih.gov/projects/openportal/ Every other Friday 2pm Eastern The OpenPortal is a collaborative effort to develop an open, site neutral and easily extensible Web service allowing users to browse, search, and visualize ontologies stored in LexGrid repositories. Participation from NCBO & others. Will inform future changes to the LexBIG model and service layers.

33. Project Links LexBIG Project http://gforge.nci.nih.gov/projects/lexbig/ NCI BioPortal Project https://gforge.nci.nih.gov/projects/lex-browser/ NCI BioPortal Site http://bioportal.nci.nih.gov/ncbo/faces/index.xhtml Open Terminology Portal Project https://gforge.nci.nih.gov/projects/openportal/

34. Q & A

35. Additional Materials

36. System.out.println("Example double restriction query with additional application of sort criteria and restricted return values"); //Declare the service... LexBIGService lbs = new LexBIGServiceImpl(); //Start with an unconstrained set of all codes for the vocabulary... CodedNodeSet cns = lbs.getCodingSchemeConcepts("NCI_Thesaurus", null, false); //Constrain to concepts with designations (assigned text presentations) //that contain text that sounds like ‘heart ventricle’ cns.restrictToMatchingDesignations("hart ventrikle", SearchDesignationOption.ALL, MatchAlgorithms.DoubleMetaphoneLuceneQuery.toString(), null); //Further restrict the results to concepts with a semantic type of //'Anatomical Structure'. cns.restrictToMatchingProperties( Constructors.createLocalNameList("Semantic_Type"), "Anatomical Structure", "exactMatch", null); LexBIG API - Example

37. //Indicate that the resulting list should be sorted, //with best results first and then sorted by code if there is a tie. SortOptionList sortCriteria = Constructors.createSortOptionList(new String[]{"matchToQuery", "code"}); //Indicate to return only the assigned UMLS_CUI and textualPresentation properties. LocalNameList restrictTo = ConvenienceMethods.createLocalNameList(new String[]{"UMLS_CUI", "textualPresentation"}); //Still nothing computed yet! //Perform the query and resolve the sorted/filtered list, //with a maximum of 6 items returned... ResolvedConceptReferenceList list = cns.resolveToList(sortCriteria, restrictTo, 6); //Print the results... ResolvedConceptReference[] rcr = list.getResolvedConceptReference(); for(ResolvedConceptReference rc : rcr) System.out.println("Resolved Concept: " + ObjectToString.toString(rc)); LexBIG API - Example

38. LexBIG Model Harmonization These slides are examples of the harmonization process.

39. ConceptReferenceList as it appeared in the original EA representation LexBIG Model Harmonization

40. ConceptReferenceList following harmonization to caCORE modeling requirements LexBIG Model Harmonization

41. SIW output prior to Harmonization/and annotation. LexBIG Model Harmonization

42. After Harmonization and prior to first pass of the annotation process LexBIG Model Harmonization

43. Result’s of automated first pass of the SIW automated annotation tool. LexBIG Model Harmonization

44. Documentation of Harmonization requirements LexBIG Model Harmonization