OpenBELRepurposable and computable knowledgefrom biological findings extracted from the

literatureSLA PHT Winter Virtual Conference • 07 December 2012

William Hayes, Ph.D., Senior VP Platform DevelopmentTed Slater, CTO OpenBEL 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,

butthis may be accompanied by

a $1,000,000 interpretation.”

- Bruce 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 I2E BEL

I2E 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

OpenBELOverview of

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

The BEL Language

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

BEL Statements

Term Expression Relationship Term Expression

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.

Subject Predicate Object

decreases

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” “RNA expression of RBL2 is directly mediated via activation of the FOXO3 transcription factor”

“LY294002 inhibits the activity of the PI3K alpha catalytic subunit” “LY294002 inhibits the activity of the PI3K alpha catalytic subunit”

XYZ Corp Document 12345XYZ Corp Document 12345

J Biol Chem 2002 Nov 22 277(47) 45276-84

J Biol Chem 2002 Nov 22 277(47) 45276-84

BEL Statement AnnotationsProvide 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”)

Assemble Facts asComputable Models

BELstatements…

…assembleinto 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

Assembled Model

Hypothesis NetworkRCR

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 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

The OpenBEL Consortium

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 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 OpenBEL to ensure that it remains a successful, thriving, and growing platform

OpenBEL Ecosystem

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

KAM NavigatorExample using

Triptych.js

http://www.triptych.js.com/

Demonstration of

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?

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

Thank You!

Questions? Contactinfo@openbel.org or visit http://openbel.org

Get OpenBEL athttps://github.org/OpenBEL