1. O pen BEL Repurposable and computable knowledge from biological findings extracted from the literature SLA PHT Winter Virtual Conference 07 December 2012 William Hayes, Ph.D., Senior VP Platform Development Ted Slater, CTO OpenBEL Consortium Selventa, Inc.

2. Mission Librarians Information Analysts No longer sufficient to Provide documents or books Run searches Literature is only valuable if you can use it Must help to build and curate mission-critical databases and knowledge bases

3. Purpose Why is knowledge representation important? What are issues that arise from using Excel as your only database tech? How does BEL fit?

4. We are close to having a $1,000 genome sequence, but this may be accompanied by a $1,000,000 interpretation. - Bruce Korf, Former President of the American College of Medical Genetics

6. Knowledge Representation is important. So, if youre still doing it the way you did 40 years ago…

8. Linguamatics I2E BEL

9. I2E Pilot for BEL

10. Causal Biology? Its likely that, to this day, you havent been able to buy or develop a single knowledge base of causal biology you could use effectively to Understand disease biology Do pathway walking Predict, describe, and leverage mechanisms of action and biomarkers competitively

11. O PEN BEL Overview of

12. What is OpenBEL? The BEL Language Biological Expression Language Subject-predicate-object triple-based, represents causal relationships in scientific findings 10 years of continuous use and development at Selventa The BEL Tools Open source (Apache license) Knowledge acquisition & management Computable graph knowledge bases from BEL statements APIs, other support http://openbel.org

13. The BEL Language

14. BEL Highlights BEL Terms Represent types of abundances or processes Based on external vocabularies and ontologies Can be derived as functions of other terms BEL Statements Correspond to a specific finding Express a relationship between terms Retain context and provenance via annotations

15. BEL Statements Term ExpressionRelationshipTerm Expression a(CHEBI:corticosteroid) -| bp(NCI: Tissue Damage ) The abundance of molecules designated by the namecorticosteroid in the CHEBI namespace. The biological process designated by the nameTissue Damage in the NCI namespace. SubjectPredicateObject decreases

16. Capture and Use Scientific Findings Scientific Literature Original Research a(PubChem:3973) -| kin(p(HGNC:PI3KCA)) tscript(p(HGNC:FOXO3)) => r(HGNC:RBL2) RNA expression of RBL2 is directly mediated via activation of the FOXO3 transcription factor LY294002 inhibits the activity of the PI3K alpha catalytic subunit XYZ Corp Document 12345 J Biol Chem 2002 Nov 22 277(47) 45276-84

17. BEL Statement Annotations Provide Context & Provenance SET Citation = { PubMed, J Mol Med (Berl). 2003 Mar;81(3):168-74., 12682725 } SET Evidence = high-dose steroid treatment decreases vascular inflammation and ischemic tissue damage after myocardial infarction and stroke through direct vascular effects involving the nontranscriptional activation of eNOS SET Tissue = vascular system SET Disease = Stroke a(CHEBI:corticosteroid) -| bp(NCI: Tissue Damage )

18. Assemble Facts as Computable Models BEL statements… …assemble into models… …for use in applications

19. BEL andReverse Causal Reasoning RCR – Using computable models built from BEL sources to generate mechanistic hypotheses based on high-throughput data. BEL Documents Assembled ModelHypothesis NetworkRCR

20. The BEL Tools

21. A set of BEL-based applications and APIs that work together to support Knowledge acquisition and management Knowledge publishing Knowledge use

22. BEL Tools Components BEL Framework v2.0 comprises BEL Compiler/Assembler Creates KAMs from BEL documents Knowledge Assembly Models (KAMs) Navigable networks (graphs) of biological facts APIs Java and Web Services Application Programming Interfaces for interacting with KAMs stored in KAM Stores Utilities Validating and converting BEL documents; managing KAMs; format conversions; etc. Eclipse-based BEL Editor for editing BEL documents BEL Cytoscape plug-in for network visualization

23. The OpenBEL Consortium

24. Promote, Protect, Standardize Members of the OpenBEL Consortium proudly support Driving adoption and evolving the standards Increasing the amount of BEL content and number of BEL tools available to the community Increasing the number of people knowledgeable about OpenBEL through training, education, and publication Facilitating crucial administrative, technical, and legal functions for the community to enable them to continue to advance the platform Serving as a proxy between the academic community, the healthcare and life sciences industry, publishers, and tools & services providers to ensure everyones needs are best understood and that collaboration solutions are optimized Holding neutral collaboration and legal events to ensure the platform is advanced and protected Serving as the neutral voice for OpenBEL to ensure that it remains a successful, thriving, and growing platform

25. OpenBEL Ecosystem

26. BEL for BioPharma Library services - capturing causal biology for use in R&D (disease biology, MoA, Toxicology, Clinical Trials, Drug Safety) Integrating databases (Ingenuity, AriadneGenomics, GeneGo, internal research requests) into single KB Model Organism Translatability - e.g. how to check if mouse biology maps well with human biology for pre-clinical drug studies Disease vs Normal Biology Comparisons - comparing known biological differences between disease and normal states in an organism's tissue Assay Development - add tool compound and drug/target relations into BEL Network to aid development of biological assays

27. KAM N AVIGATOR Example using

28. T RIPTYCH. JS HTTP :// WWW. TRIPTYCH. JS. COM / Demonstration of

29. Starting Questions Does treating mouse model X with drug Y correlate to human biology? What is known biology for EGFR? Tissues expressed, interacting proteins, associated disease conditions, … What is found in the literature to associate kidney failure to steatosis (liver adverse event)? We need more detailed and highly contextualized information for Pathway X than what is in Ingenuity/GeneGo/etc How could using drug X with MoA Y affect tissue Z?

30. Future Enhancements BEL Statement/Script Creation Dynamic Web-based Statement Editor (Q2 2013) Curation Tool/PDF Reader Plugin (est Q4 2013) Academic UIMA-based text mining workflows for KB creation

31. Thank You! Questions? Contact info@openbel.orginfo@openbel.org or visit http://openbel.orgrg Get OpenBEL at https://github.org/OpenBEL