1. How Ontologies Add Value BioPAX: Biological Pathway Data Exchange Ontology Joanne Luciano BioPAX Workgroup (biopax.org)biopax.org BioPathways Consortium Liaison (biopathways.org) 3 May 2005 KM Pro Forum Bentley College, Waltham MA, USA

2. 3 May 20052 Introduction BioPAX = Biopathway Exchange Language Emerged at ISMB conceived at ISMB ’01 born at ISMB ’02 crawling at ISMB ’03 (Level 0.5) walking at ISMB ’04 (Level 1.0) now in the “terrible twos”

3. 3 May 20053 Ontology Intro Natural language does a poor job at conveying complex information without ambiguity Ontologies provide a means to give concise meanings to pieces of data from a particular domain –Thereby facilitating computational operations on the data Ontologies are becoming increasingly common in the biological community –See http://obo.sourceforge.net/obo.htmhttp://obo.sourceforge.net/obo.htm

4. 3 May 20054 Ontology: Components Class hierarchy: chemical  protein Relations & attributes: fields (slots) on the classes, can be other classes Constraints: Define allowable values and connections within an ontology Objects: instances of classes Values: occupy slots Controlled vocabularies (CVs) BioPAX will use class, attributes, constraints, values and CVs. Objects are user responsibility * From Peter Karp, “Ontologies: Definitions, Components, Subtypes”, SRI International, presentation available at http://www.biopax.orghttp://www.biopax.org

5. 3 May 20055 What is a Pathway? Depends on who you ask! Metabolic Pathways Molecular Interaction Networks Signaling Pathways Gene Regulation GlycolysisProtein-ProteinApoptosisLac Operon

6. 3 May 20056 High Throughput Experimental Methods PubMed Existing Literature Microarray Two-Hybrid Mass Spectrometry Genetics Multiple Pathway Databases Integration Nightmare! Protein modifications Function Interaction Data Expression

7. 3 May 20057 So many pathway databases… Each has its own data model, format, and data access methods Source: Pathway Resource List (http://cbio.mskcc.org/prl/)http://cbio.mskcc.org/prl/

8. 3 May 20058 WIT BioCyc Reactome aMAZE KEGG BIND DIP HPRD MINT IntAct PSI format CSNDB TRANSPATH TRANSFAC PubGene GeneWays  Research Community Needs Pathway Databases Semantic Aggregation, Integration, Inference (Pedantic Aggravation, Irritation, and Interference)

9. 3 May 20059 Without BioPAXWith BioPAX Common “computable semantic” enables scientific discovery Over 170 DBs and tools Database Application User A Common Exchange Language Promotes collaboration (big science), accessibility

10. 3 May 200510 Closes Gaps in Pathway Data Space Exchange Language Domain BioPAX PSI-MI 2 SBML, CellML Genetic Interactions Molecular Interactions Pro:Pro All:All Interaction Networks Molecular Non-molecular Pro:Pro TF:Gene Genetic Regulatory Pathways Low Detail High Detail Database Exchange Formats Simulation Model Exchange Formats Rate Formulas Metabolic Pathways Low Detail High Detail Biochemical Reactions Small Molecules Low Detail High Detail

11. 3 May 200511 Design Goals Encapsulation: An entire pathway in one record Compatible: Use existing standards wherever possible Computable: From file reading to logical inference Successful: Buy-in from the research community

12. 3 May 200512 Technical Goals Interoperability –Integration and exchange of pathway data –Interchange through a common (standard) representation –accommodate existing database representations –provide a basis for future databases –enables development of tools for searching and reasoning over the data base Development of tools and API to facilitate conversion (libBioPAX)

13. 3 May 200513 Technical Goals (cont’d) Why OWL? Why OWL DL? Expressivity (biology = “complex relationships”) W3C Standard (use existing standards) “Semantic Web enabled” XML based (the exchange language in computing) Machine Computable –Facilitate integration of knowledge, data, tool development –Uncover inconsistencies and new knowledge –OWL DL Enable full reasoning capability for users from file reading to logical inference Complete: all conclusions are guaranteed to be computed Decidable: all computations will finish in finite time (with OWL Lite, short amount of time)

14. 3 May 200514 Social Logistics Get organized Make the decision & commitment 2 or 3 dedicated individuals to be the contact points Small core group –Bi-weekly conference calls, bi-monthly F2F –Commitment & resources Participants willing and able cover their costs Outside funding (DOE) Special interests and needs form subgroup task forces Core group member(s) Outside experts International representation & participation (Outreach & Community Building) conferences and mailing lists follow-up and individual Collaborate with complementary/competing representations

15. 3 May 200515 Social Logistics (cont’d) How we engendered buy in from the field which made life much easier Take things in steps: Pathway Database vision -> Data Exchange Format as 1 st step Data Exchange Format -> Release in Levels of increasing complexity Level 1 supports Metabolic pathways, Level 2 Early success leads to early adoption, leads to increased probability of overall project success. Get “buy in” and get involvement -leads to acceptance later Support the existing databases (BioCYC, WIT, BIND, etc.) –Got database sources to agree to participate in the development to assure that their DBs will be properly represented Got database sources to agree to export in the new format once it is defined

16. 3 May 200516 Social Logistics (cont’d) Get “buy in” (continued) Community Involvement and Support Core group (represents voice of community, small, committed) Mailing List User community interaction (BioPAX-Boston) Subgroups International Meetings and Presentations Tool developers Modelers Users (researchers) Ontology developers Database providers Complementary representations (SBML, CellML) Like minds General Community

17. 3 May 200517 Implementation of BioPAX Designed using GKB Editor and Protégé BioPAX uses OWL to define the “Schema” BioPAX Instances to store the data Technically, an ontology with instance data is a knowledge base

18. 3 May 200518 BioPAX – Ontology Level 1: Metabolic Pathways

19. 3 May 200519 Creating and Editing

20. 3 May 200520 OWL (schema ) Instances (Individuals) data Mapping Pathways to BioPAX

21. 3 May 200521 Mapping Pathways to BioPAX

22. 3 May 200522 Challenges & Bottlenecks Scientific –What’s a pathway? Depends on who you ask. Technical –Each own syntax & semantics –Immaturity of tools for data integration Social / Logistical –Community organization and adoption Financial –mostly volunteer of stakeholders –Dept of Energy

23. 3 May 200523 Bridging Chemistry and Molecular Biology Uniprot: P49841 Different Views have different semantics: Lenses When there is a correspondence between objects, a semantic binding is possible Apply Correspondence Rule: if ?target.xref.lsid == ?bpx:prot.xref.lsid then ?target.correspondsTo.?bpx:prot Source: Eric Neumann

24. 3 May 200524 BioPAX increases collaboration and accessibility to the field and enables 'big science' because it delivers a scalable solution Capture the complex relationships inherent in Biology Solves some nasty integration problems Saves a lot of time and money Enables Computable Biology

25. 3 May 200525 BioPAX Supporting Groups Groups Memorial Sloan-Kettering Cancer Center: G. Bader, M. Cary, J. Luciano, C. Sander SRI Bioinformatics Research Group: P. Karp, S. Paley, J. Pick University of Colorado Health Sciences Center: I. Shah BioPathways Consortium: J. Luciano, E. Neumann, A. Regev, V. Schachter Argonne National Laboratory: N. Maltsev, E. Marland Samuel Lunenfeld Research Institute: C. Hogue Harvard Medical School: E. Brauner, D. Marks, J. Luciano, A. Regev NIST: R. Goldberg Stanford: T. Klein Columbia: A. Rzhetsky Dana Farber Cancer Institute: J. Zucker Collaborating Organizations: Proteomics Standards Initiative (PSI) Systems Biology Markup Language (SBML) CellML Chemical Markup Language (CML) Databases BioCyc (www.biocyc.org) BIND (www.bind.ca) WIT (wit.mcs.anl.gov/WIT2) PharmGKB (www.pharmgkb.org)www.pharmgkb.org Grants Department of Energy (Workshop) The BioPAX Community

26. 3 May 200526 Thank you! Questions?