EBI : 14-01-101

Bio2RDF and Beyond! Large Scale, Distributed Biological Knowledge Discovery

Michel Dumontier, Ph.D.Associate Professor of Bioinformatics

Carleton University

Department of BiologySchool of Computer Science

Institute of BiochemistryOttawa Institute of Systems Biology

Ottawa-Carleton Institute of Biomedical Engineering

EBI : 14-01-102 Carole Goble (ISWC 2005)

Web-based Knowledge Discovery a very painful process

EBI : 14-01-103

Syntactic Web…It takes a lot of digging to get answers

EBI : 14-01-104

Portals provide structured informationand give better results

EBI : 14-01-105

Surface web:167 terabytes

Deep web:91,000 terabytes

545-to-one

We need to expose the deep web

EBI : 14-01-106

Data silos – not made for sharing

EBI : 14-01-107

How do we integrate these resources?

EBI : 14-01-108

We want to simultaneously

query the 1000+ biological databases

EBI : 14-01-109

The Semantic Web is a web of knowledge.

It is about standards for publishing, sharing and querying knowledge drawn from diverse sources

It enables the answering of sophisticated questions

EBI : 14-01-1010

A growing web of linked data

EBI : 14-01-1011

Life Science Data Contributors

• HCLS (LODD)• Neurocommons• Bio2RDF

EBI : 14-01-1012

Resource Description Framework (RDF)

Uniform Resource Identifier (URI) can be used as entity names

Bio2RDF specifies the naming convention

http://bio2rdf.org/uniprot:P05067

is a name for Amyloid precursor protein

http://bio2rdf.org/omim:104300

is a name for Alzheimer disease

uniprot:P05067

omim:104300

Allows one to talk about anything

EBI : 14-01-1013

Resource Description Framework (RDF)

uniprot:Protein

is a

A RDF statement consists of:– Subject: resource identified by a URI– Predicate: resource identified by a URI– Object: resource or literal

uniprot:P05067

Allows one to express statements

EBI : 14-01-1014

Multi-Source Data Integration

uniprot:P05067 go:Membrane

uniprot:Proteinis a

located in

uniprot:P05067

uniprot:P05067 uniprot:P05067interacts with

UniProt

Gene Ontology

uniprot:P05067

has name

located in

interacts with

Unified view

+

+

iRefIndex

depends on consistent naming

go:Membrane

uniprot:Protein

uniprot:P05067

EBI : 14-01-1015

Building statements creates knowledge

uniprot:P05067

Protein

is a

omim:104300

Disease

is a

is involved in

Amyloid precursor

protein

label

AlzheimerDisease

label

EBI : 14-01-1016

RDF/XML<?xml version="1.0"?><rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:u="http://bio2rdf.org/uniprot:"

<rdf:Description rdf:about=“&u;Q16665"> <rdf:type rdf:resource=“&u;Protein"/> </rdf:Description></rdf:RDF>

PREFIX u: <http://bio2rdf.org/uniprot:>

<u:Q16665> a <u:Protein> .

RDF/N3

RDF has multiple representations

EBI : 14-01-1017

Bio2RDF is a framework to create and provision linked data networks

Francois Belleau, Laval UniversityMarc-Alexandre Nolin, Laval University

Peter Ansell, Queensland University of TechnologyMichel Dumontier, Carleton University

EBI : 14-01-1018

Bio2RDF’s RDFized data fits together

EBI : 14-01-1019

Bio2RDF now serving over 5 / 15 billion triples of linked biological data

EBI : 14-01-1020

Bio2RDF linked data

Bioinformatics Discovery Registry• SharedName initiative to provide stable URI patterns for data records.• We added the relationship between entities and records

Directory Service• ~1700 datasets & dozens of resolvers.

Discovery Service• Registry links entities to data records, their formats (RDF/XML, HTML, etc)

and provider (Bio2RDF, Uniprot)

Redirection Service• Automatic redirection to data provider document

EBI : 14-01-1022

something you can lookup or search for with rich descriptions

EBI : 14-01-1023

Bio2RDF: Raw Data!

EBI : 14-01-1024

SPARQL is the new cool kid on the query block

SQL SPARQL

EBI : 14-01-1025

Bio2RDF’s describe service uses SPARQL

CONSTRUCT {?s ?p ?o .

}WHERE {?s ?p ?o .FILTER(?s = <http://bio2rdf.org/ns:id>).

}

Sent to http://ns.bio2rdf.org/sparql?query=...

http://bio2rdf.org/ns:id

EBI : 14-01-1026

Bio2RDF’s search service uses SPARQLhttp://bio2rdf.org/search/hexokinase

kegguniprot

gene

bio2rdf.org

EBI : 14-01-1027

Bio2RDFScalable, Decentralized Data ProvisionGlobally Mirrored and Point Provision

Customizable Query Resolution

EBI : 14-01-1028

Customizable Configuration (in N3)Single Query, Single Provider

EBI : 14-01-1029

Query Resolution

EBI : 14-01-1030

EBI : 14-01-1031

700,000 queries in November 2009

EBI : 14-01-1032

Yai for data!

But how do we discover more than what was in the data?

EBI : 14-01-1033

Ontology as Strategy

EBI : 14-01-1034

uniprot:P05067

Uniprot:Protein

is a

chebi:PolyatomicEntity

is a

is a

Reasoning and Inference through Semantics

fact

ontology

Knowledge base

EBI : 14-01-1035

The Web Ontology Language (OWL) Has Explicit Semantics

Can therefore be used to capture knowledge in a machine understandable way

Over 170 bio-ontologies

EBI : 14-01-1036

From linked data to linked knowledge through syntactic and semantic normalization.

Multiple Ways To Represent Knowledge

Three ways to model the relationship between a protein and the volume it occupies.

EBI : 14-01-1039

Web-based Knowledge DiscoverySome of our queries need services

EBI : 14-01-1040

The Holy Grail:

Align the promoters of all serine threonine kinases involved exclusively in the regulation of cell sorting during wound healing in blood vessels.

Retrieve and align 2000nt 5' from every serine/threonine kinase in Mus musculus expressed exclusively in the tunica [I | M |A] whose expression increases 5X or more within 5 hours of wounding but is not activated during the normal development of blood vessels, and is <40% similar in the active site to kinases known to be involved in cell-cycle regulation in any other species.

EBI : 14-01-1041

Semantic Automated Discovery and Integration

http://sadiframework.org

Mark Wilkinson, UBCMichel Dumontier, Carleton UniversityChristopher Baker, UNB

SADI – described oriented service matching based on

registered predicates

EBI : 14-01-1043

EBI : 14-01-1044

What pathways does UniProt protein P47989 belong to?

PREFIX pred: <http://sadiframework.org/ontologies/predicates.owl#>PREFIX ont: <http://ontology.dumontierlab.com/>PREFIX uniprot: <http://lsrn.org/UniProt:>

SELECT ?gene ?pathway WHERE {

uniprot:P47989 pred:isEncodedBy ?gene . ?gene ont:isParticipantIn ?pathway .

}

EBI : 14-01-1045

SADI

• Describe the input and output using OWL-DL classes• Subject of input and output must be the same• Web services correspond to predicates• Biocatalogue to register SADI-compliant services• Simplified migration path for existing web services (java, perl)

EBI : 14-01-1046

Build aknowledge basefrom a series of questions

EBI : 14-01-1047

You want to join the knowledge web

EBI : 14-01-1048

Share your data

EBI : 14-01-1049

Build semantic web services

EBI : 14-01-1050Get to where you want to be … faster!

EBI : 14-01-1051

Next Steps

Service and Data Buildout Formal Partnerships

Applications

EBI : 14-01-1052

dumontierlab.commichel_dumontier@carleton.ca

EBI : 14-01-1053

We’re interested in Personalized Medicine

The ability to offer • The Right Drug• To The Right Patient• For The Right Disease• At The Right Time• With The Right Dosage

Genetic and metabolic data will allow drugs to be tailored to patient subgroups

54 EBI : 14-01-10

EBI : 14-01-1055

PHARMGKB is an emerging resource for pharmacogenomics

+ Role of genes, gene variants , drugs + pharmacokinetics + pharmacodynamics + clinical outcomes. + Links to publications

- Natural language descriptions- Variant details in publications

EBI : 14-01-1056

contains statements from 11/40 relevant publications involving 45 genes / gene variants, 57 drugs annotated with 19 classes of antidepressants, 45 drug treatments, 47 drug-gene interactions, 29 clinical outcomes, 10 drug-induced side-effects, and 8 gene-disease interactions.

PHARMACOGENOMICS OF DEPRESSION KNOWLEDGE BASE

EBI : 14-01-1057

Nortriptyline induced side effects for ABCB1 gene variants

‘side effect’ that ‘is realized by’ some (‘drug treatment’ that ‘involves’ some ‘nortriptyline’ and

‘involves’ some (‘variant of’ some ‘ABCB1’))

QUERYING THE PDKBProtégé 4, FaCT++, DL Query Tab

postural hypotension is a side effect of nortriptyline treatment of depression for individuals presenting the 3435C>T genotype