Open BEL Repurposable and computable knowledge from biological

Open. 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 Open. BEL Consortium Selventa, Inc.

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

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

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

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

Linguamatics I 2 E BEL

I 2 E Pilot for BEL

Causal Biology? • It’s likely that, to this day, you haven’t 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

Overview of OPENBEL

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

The BEL Language

BEL Highlights • BEL Terms • • Based on external vocabularies and ontologies • • Represent types of abundances or processes 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

BEL Statements Term Expression Relationship Term Expression Subject Predicate Object decreases a(CHEBI: corticosteroid) -| bp(NCI: ”Tissue Damage”) The abundance of molecules designated by the name “corticosteroid” in the CHEBI namespace. The biological process designated by the name “Tissue Damage” in the NCI namespace.

Capture and Use Scientific Findings “RNA expression of RBL 2 is directly mediated via activation of the FOXO 3 transcription factor” Scientific Literature tscript(p(HGNC: FOXO 3)) => r(HGNC: RBL 2) J Biol Chem 2002 Nov 22 277(47) 45276 -84 “LY 294002 inhibits the activity of the PI 3 K alpha catalytic subunit” Original Research a(Pub. Chem: 3973) -| kin(p(HGNC: PI 3 KCA)) XYZ Corp Document 12345

BEL Statement Annotations Provide Context & Provenance SET Citation = {“Pub. Med”, “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 e. NOS” SET Tissue = “vascular system” SET Disease = “Stroke” a(CHEBI: corticosteroid) -| bp(NCI: ”Tissue Damage”)

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

BEL and “Reverse Causal Reasoning” RCR – Using computable models built from BEL sources to generate mechanistic hypotheses based on high-throughput data. BEL Documents RCR Assembled Model Hypothesis Network

The BEL Tools

The BEL Tools • A set of BEL-based applications and APIs that work together to support • Knowledge acquisition and management • Knowledge publishing • Knowledge use

BEL Tools Components • BEL Framework v 2. 0 comprises • BEL Compiler/Assembler • • Knowledge Assembly Models (KAMs) • • Navigable networks (graphs) of biological facts APIs • • Creates KAMs from BEL documents 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

The Open. BEL Consortium

Promote, Protect, Standardize • Members of the Open. BEL 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 Open. BEL 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 everyone’s 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 Open. BEL to ensure that it remains a successful, thriving, and growing platform

Open. BEL Ecosystem

BEL for Bio. Pharma • Library services - capturing causal biology for use in R&D (disease biology, Mo. A, Toxicology, Clinical Trials, Drug Safety) • Integrating databases (Ingenuity, Ariadne. Genomics, Gene. Go, 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

Example using KAM NAVIGATOR

Demonstration of TRIPTYCH. JS HTTP: //WWW. TRIPTYCH. JS. COM/

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/Gene. Go/etc • How could using drug X with Mo. A Y affect tissue Z?

Future Enhancements • BEL Statement/Script Creation • Dynamic Web-based Statement Editor (Q 2 2013) • Curation Tool/PDF Reader Plugin (est Q 4 2013) • Academic UIMA-based text mining workflows for KB creation

Thank You! Questions? Contact info@openbel. org or visit http: //openbel. org Get Open. BEL at https: //github. org/Open. BEL