Triples for the People (Scientists): Liberating biological knowledge with the Semantic Web

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Triples for the People (Scientists): Liberating biological knowledge with the Semantic Web

Ottawa/Chicago Semantic Web Meetup : 23-11-09

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

Ottawa/Chicago Semantic Web Meetup : 23-11-092 Carole Goble (ISWC 2005)

Web-based Knowledge Discovery a very painful process


With current web search engines…It takes a lot of digging to get answers


Portals provide structured informationand give better results


Surface web:167 terabytes

Deep web:91,000 terabytes

545-to-one

We need to expose the deep web


Data silos – not made for sharing


We want to simultaneously

query the 1000+ biological databases


How do we integrate these resources?


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


A growing web of linked data


Bio2RDF provides a framework to glue to link data networks together


Resource Description Framework (RDF)

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

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


Resource Description Framework (RDF)

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


Multi-Source Data Integration

uniprot:P05067 Membrane

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

Membrane

Protein

uniprot:P05067


Building statements creates knowledge

uniprot:P05067

Protein

is a

omim:104300

Disease

is a

is involved in

Amyloid precursor

protein

label

AlzheimerDisease

label


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

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

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

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

RDF/N3

RDF has multiple representations

http://www.w3.org/1999/02/22-rdf-syntax-ns



http://purl.uniprot.org/uniprot/

http://purl.uniprot.org/uniprot/


Bio2RDF’s RDFized data fits together


Bio2RDF serves up over 4 billion triples of linked biological data


something you can lookup or search for with rich descriptions


Bio2RDF: Raw Data!


SPARQL is the new cool kid on the block

SQL SPARQL


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

http://ns.bio2rdf.org/sparql?query




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

kegguniprot

gene

bio2rdf.org

http://bio2rdf.org/search/hexokinase


Yai for data!

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


Ontology as Strategy


uniprot:P05067

Protein

is a

Molecule

is a

is a

Reasoning and Inference through Semantics

fact

ontology

Knowledge base


Logic Based Ontologies Are Conceptual Lego


A simple ontology: Animals

Living Thing

Grass

Animal

Plant

Tree

Body Part

Arm

Leg

Person

Cow

Carnivore

Herbivore

eats

eats

eatshas part


The Web Ontology Language (OWL) Has Explicit Semantics

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


• Subsumption is the primary axis (relationship) in OWL• Superclass/subclass relationship, “is a”• All members of a subclass must be members of its superclasses

• All Proteins are also Molecules• Protein is a subclass of Molecule• Molecule is a superclass of Protein• Molecule subsumes Protein

owl:Thing superclass of all Classes

Protein

Molecule

Key idea: Subsumption


Key Idea: Disjunction

Stating that 2 classes are disjoint means

DNA

= individual

Something cannot be both an Protein and DNA

Protein

This can help us find errors

32

Transcription Factor

“A protein that binds to DNA and regulates gene expression.


By stating the necessary and sufficient conditions we discover new knowledge

Key Idea: Class equivalence

Ottawa/Chicago Semantic Web Meetup : 23-11-0933Barry smith

Many ontologies required

Over 170 bio-ontologies


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

35 Ottawa/Chicago Semantic Web Meetup : 23-11-09


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


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


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


Web-based Knowledge DiscoverySome of our queries need services


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% homologous in the active site to kinases known to be involved in cell-cycle regulation in any other species.



Semantic Automated Discovery and Integration

http://sadiframework.org

Mark Wilkinson, UBCMichel Dumontier, Carleton UniversityChristopher Baker, UNB

http://sadiframework.org/


As OWL Axioms

HomologousGeneImage is owl:equivalentTo {

Gene Q hasImage image P

Gene Q hasSequence Sequence Q

Gene R hasSequence Sequence R

Sequence Q similarTo Sequence R

Gene R = “my gene of interest” }


Build aknowledge basefrom a series of questions


You want to join the knowledge web


Share your data


Bridge your data with others in semantic communities


Time-sensitive or frequently updated data is one way to encourage more visits.




The Knowledge Web

• Merging data & services

• Reasoning & question answering

• Persistent (RESTful)

• Trust & Security

Data consumers must be able to rely upon your data to use it as a foundation for their own applications.


Join the knowledge web.


[email protected]

Health & Medicine

Triples for the People (Scientists): Liberating biological knowledge with the Semantic Web