Post on 19-Dec-2015
transcript
Dynamic Semantic Metadata on Web Resources in Biomedicine
Tim ClarkHarvard Medical School &
Massachusetts General Hospital
RPI Tetherless World ConstellationMay 3, 2011
Copyright 2010 Massachusetts General Hospital. All rights reserved.
Outline of talk
Biomedical web data integration challenges Requirements to cure complex disorders Catch-22 for semantic data in medicine
Web 3.0 and semantic metadata Injecting semantics into the existing
ecosystem Integrating ontologies, documents &
data Annotation Ontology & Annotation
Framework Hypothesis management (vs. KM)
Some complex neurological disorders
Alzheimer Disease
Huntington’s Disease
Nicotine Addiction
SchizophreniaBipolar
DisorderAlcohol
addiction
AutismParkinson’s
DiseaseALSNeuropathic
PainMajor
Depressive Disorder
Alzheimer’s + Addiction + Depression
Yearly mortality (U.S.) = 642,00 people
Yearly costs (U.S.) = $676 B / 4.7% GDP
Prevalence = 5.3 M + 76 M + 14.4 M
= 95.7 M people
create hypothesis
design experiment
run experiment collect data
interpret data
share interpretations
synthesize knowledge
“hippocampal atrophy and Aβ load predicted shorter time-to-progression”
MCI progressors non progressors
PET imaging of PIB (radiolabelled compound binds amyloid beta A4 protein)
MRI imaging of brain structure showing loss of hippocampal volume
Brain. 2010 Nov;133(Pt 11):3336-3348.
= 218 subjects +
Alzheimer Disease
Parkinson’s Disease
Schizophrenia
Autism
Bipolar DisorderDrug Addiction
Huntington’s Disease
ALS
Depression
dopaminergic pathway
α-synuclein, β-amlyoid
α-synuclein, Tau
chr 16p11.2 CNV
chr 16p11.2 CNV
CRF, glutaminergic system, dopamine, amygdala …
Alzheimer Disease
Parkinson’s Disease
Schizophrenia
Autism
Bipolar DisorderDrug Addiction
Huntington’s Disease
ALS
Depression
SIRT2
1. We want to organize all the known facts in neurobiology so we can mash them up.
2. There are no “facts” in neurobiology, except uninteresting ones.
3. All we have, are assertions supported by evidence, of varying quality.
Science is part of an information ecosystem
1667 2010
Printing Press Web
We scientists do not attend professional meetings to present our findings ex cathedra, but in order to argue.
John Polanyi, FRS, Nobel Laureate
University of Manchester
What is Web 3.0?
Social Web (Web 2.0, read/write)
Shared annotation with controlled terminology systems (Sem Web)
+
How does Web 3.0 help?
Information sharing within communities or tasks via Social Web (Web 2.0), wikis and forums
Information “permeability” across pharma R&D projects / domains / pipeline stages via shared metadata (semantic annotation)
Web 3.0 improves cross-domain Signal to Noise, institutional memory & data “findability”
Supervised automatic annotation
Genes
Proteins
Biological Processes
Chemical Compounds
Antibodies
Cells
Brain anatomy
…
Annotation Ontology & SWAN Annotation Framework
Annotation Ontology (AO) is a domain-independent Web ontology. Links document fragments to ontology
terms. Metadata separate from annotated
documents. SWAN AF manages document
annotation. Interfaces to textmining svcs & supports
curation.Collaborating with
NCBO, UCSD, Elsevier, USC, Manchester, EMBL, Colorado, EBI, etc…
Annotation Ontology (AO)
Text
Shared metadata
Supervised textmining
2) Automatic annotation
Dr.
Pao
lo C
icca
rese
– O
ct 8
, 20
10
Term localization and curationD
r. P
aolo
Cic
care
se –
Oct
8,
2010
Localization in text
Localization on image
Complements and can support
Semantics on documents (SESL) Vocabulary standards & terminology
development Document & data managementCollaboratories & web communitiesHypothesis management (SWAN)Nanopublications (OpenPHACTS)
What is Hypothesis Management?
Model the thinking behind your research Database it, web-ify it, RDF-ize it, share it Link the Models / Hypotheses to
Claims / Interpretations Evidence (publications, experiments, data) Supporting and contradictory claims from others Evidence for these other claims
Web 3.0: share, compare and discuss Manage knowledge while creating it
Can be public, private, or semi-private
An Alzheimer hypothesis in SWAND
r. P
aolo
Cic
care
se –
Oct
8,
2010
Exploring a claimD
r. P
aolo
Cic
care
se –
Oct
8,
2010
The SWAN ontology
Dr.
Pao
lo C
icca
rese
– O
ct 8
, 20
10
Cognitive
Deficits(S)
BACE1(O)
Relate to(p)
provenance
context
With thanks to Barend Mons and Paul Groth…
Mons / Groth model of a nanopublication
Claim in a graph with authorship
swande:Claim
<http://tinyurl.com/4h2am3a>
Intramembranous Aβ behaves as chaperones of other membrane proteins
rdf:type
dct:title
G1
<http://example.info/person/1>
pav:authoredBy
Vincent Marchesi
foaf:name
foaf:Person
rdf:type
pav: http://purl.org/pav/provenance/2.0/ foaf: http://xmlns.com/foaf/0.1/
G2
Adding provenance
swande:Claim
<http://tinyurl.com/4h2am3a>
Intramembranous Aβ behaves as chaperones of other membrane proteins
rdf:type
dct:title
G1
<http://example.info/person/1>
pav:authoredBy
G2
<http://example.info/person/0>
pav:curatedBy
G4
Gwen Wong
foaf:name
foaf:Person
rdf:type
Author’s evidence
swande:Claim
<http://tinyurl.com/4h2am3a>
Intramembranous Aβ behaves as chaperones of other membrane proteins
rdf:type
dct:title
G1
<http://example.info/person/1>
pav:contributedBy
<http://example.info/citation/1>
swanrel:referencesAsSupportiveEvidence
G5
G6
Translating into HyQue-triples
G8
<http://example.info/alzswan:statement_f3556dcfc331d9b9af9d5c0cfc570ba6_event_1>
<http://bio2rdf.org/go:0051087>
rdf:type
Event of type GO "chaperone binding"
rdfs:label
<prefix:actor_1>
<prefix:target_1>
<prefix:location_1>
<http://bio2rdf.org/chebi:53002>
<http://bio2rdf.org/mesh:D008565>
<http://bio2rdf.org/go:0005886>
rdf:type
rdf:type
rdf:type
rdfs:label “Beta amyloid”
rdfs:label “Membrane protein”
rdfs:label “Plasma membrane”
With many thanks to Nigam Shah, Stanford University
Adding the provenance
Hyque triples
G8
<http://example.info/person/2>
pav:contributedBy
Nigam Shah
foaf:name
foaf:Person
rdf:typeG9
Connecting SWAN Claim and Hyque triples
swande:Claim
<http://tinyurl.com/4h2am3a>
Intramembranous Aβ behaves as chaperones of other membrane proteins
rdf:type
dct:title
G1
Hyque triples
G8
swanrel:derivedFrom
Drug Discovery Hypotheses
Target / pathway hypotheses will be linked to: Pathway & target relation to disease, Target selection criteria, Validation assays and criteria, Experiment (assay) provenance, Experimental data and computations, Scientist remarks, findings and
discussion. Start as a relatively simple model
and extend
Drug Development Hypotheses
Hypotheses of therapeutic action for compounds and scaffolds will be linked to Hypothesis / results for individual
assays, Experiment (assay) provenance, Experimental data, Group annotation, Internal databases etc.
Start as a relatively simple model and extend
Open Enterprise Semantic Model
Web 3.0 + T-R + PharmaInformation ecosystem
Some other applications
Research reproducibility Linking data to documents at time of
publications Citation of reagents, instruments, code,
protocolsBibliographies and citation networks
Bibliographic records and citations are metadata
Personal annotations Selective sharing and virtual
communitiesDatabase annotation
Biomedical ontology database curation projects
NASA Astrophysics Data System
What is NASA ADS? Web database comprising over 8 million
astronomy and physics papers Full-text for over 880K articles, including all
major astronomy journals NASA ADS semantic annotation
requirements Astronomical objects by catalog ID Specific telescope, type of telescope,
wavelength Investigators Grant funding sources
SummaryCuring complex medical disorders goes
hand in hand with next-gen biomedical communications
Web 3.0 provides the technology framework
Semantic annotation, hypothesis management, nanopubs: tools for next-gen biomed comms .
Requires / enables international collaborations of biomedical researchers and informaticians.
Open enterprise model with semantic metadata.
AcknowledgementsPeople
Paolo Ciccarese (Harvard) Maryann Martone (UCSD) Anita DeWaard & Tony Scerri (Elsevier) Karen Verspoor & Larry Hunter (Colorado) Adam West & Ernst Dow (Eli Lilly) Carole Goble (Manchester) Nigam Shah (Stanford / NCBO) Paul Groth (VU Amsterdam)
Funding: Elsevier, NIH, Eli Lilly, & EMD Serono
Whereas King Ptolemy, living forever, the Manifest God whose excellence is fine, son of King Ptolemy and Queen Arsinoe, the Father-
loving Gods, is wont to do many favours for the temples of Egypt and for all those who are subject to his kingship, he being a god…
English translation by R.S. Simpson