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Knowledge Enabled Information and Services Science
Semantic Web for Health Care and Biomedical Informatics
Keynote at
NSF Biomed Web Workshop, December 4-5, 2007
Amit P. Shethamit.sheth@wright.edu
Thanks Pablo Mendes, Satya Sahoo and Kno.e.sis team;Collaborators at Athens Heart Center (Dr. Agrawal), NLM (Olivier Bodenreider), CCRC, UGA (Will York), CCHMC (Bruce Aronow)
Knowledge Enabled Information and Services Science
Outline
• Semantic Web – very brief intro
• Scenarios to demonstrate the applications and benefit of semantic web technologies– Health care– Biomedical Research
Knowledge Enabled Information and Services Science
Biomedical Informatics...
Medical Informatics Bioinformatics
Etiology PathogenesisClinical findingsDiagnosisPrognosisTreatment
GenomeTranscriptome
ProteomeMetabolome
Physiome...ome
Genbank
Uniprot
Pubmed
Clinical Trials.gov
...needs a connection
Biomedical Informatics
Hypothesis ValidationExperiment design
PredictionsPersonalized medicine
Semantic WebSemantic Web research aims at research aims atproviding this connection!providing this connection!
More advanced capabilities for search, integration, analysis, linking to new insights and discoveries!
Knowledge Enabled Information and Services Science
Evolution of the Web
Web of pages - text, manually created links - extensive navigation
2007
1997
Web of databases - dynamically generated pages - web query interfaces
Web of services - data = service = data, mashups - ubiquitous computing
Web of people - social networks, user-created content - GeneRIF, Connotea
Web as an oracle / assistant / partner - “ask to the Web” - using semantics to leverage text + data + services + people
Knowledge Enabled Information and Services Science
• Ontology: Agreement with Common Vocabulary & Domain Knowledge; Schema + Knowledge base
• Semantic Annotation (meatadata Extraction): Manual, Semi-automatic (automatic with human verification), Automatic
• Reasoning/computation: semantics enabled search, integration, complex queries, analysis (paths, subgraph), pattern finding, mining, hypothesis validation, discovery, visualization
Semantic Web Enablers and Techniques
Knowledge Enabled Information and Services Science
Maturing capabilites and ongoing research
• Text mining: Entity recognition, Relationship extraction
• Integrating text, experimetal data, curated and multimedia data
• Clinical and Scientific Workflows with semantic web services
• Hypothesis driven retrieval of scientific literature, Undiscovered public knowledge
Knowledge Enabled Information and Services Science
Metadata and Ontology: Primary Semantic Web enablers
Shallow semantics
Deep semantics
Expr
essi
vene
ss,
Rea
soni
ng
Knowledge Enabled Information and Services Science
Characteristics of Semantic Web
SelfDescribing
Machine &Human
Readable
Issued bya TrustedAuthority
Easy toUnderstand
ConvertibleCan be
Secured
The Semantic Web:XML, RDF & Ontology
Adapted from William Ruh (CISCO)
Knowledge Enabled Information and Services Science
Open Biomedical Ontologies
Open Biomedical Ontologies, http://obo.sourceforge.net/
Many ontologies exist
Knowledge Enabled Information and Services Science
Drug Ontology Hierarchy (showing is-a relationships)
owl:thing
prescription_drug
_ brand_na
me
brandname_unde
clared
brandname_comp
osite
prescription_drug
monograph_ix_cla
ss
cpnum_ group
prescription_drug
_ property
indication_
property
formulary_
property
non_drug_
reactant
interaction_proper
ty
property
formulary
brandname_indivi
dual
interaction_with_prescriptio
n_drug
interaction
indication
generic_ individua
l
prescription_drug_ generic
generic_ composit
e
interaction_ with_non_ drug_react
ant
interaction_with_monograph_ix_class
Knowledge Enabled Information and Services Science
N-Glycosylation metabolic pathway
GNT-Iattaches GlcNAc at position 2
UDP-N-acetyl-D-glucosamine + alpha-D-Mannosyl-1,3-(R1)-beta-D-mannosyl-R2 <=>
UDP + N-Acetyl-$beta-D-glucosaminyl-1,2-alpha-D-mannosyl-1,3-(R1)-beta-D-mannosyl-$R2
GNT-Vattaches GlcNAc at position 6
UDP-N-acetyl-D-glucosamine + G00020 <=> UDP + G00021
N-acetyl-glucosaminyl_transferase_VN-glycan_beta_GlcNAc_9N-glycan_alpha_man_4
Knowledge Enabled Information and Services Science
Opportunity: exploiting clinical and biomedical data
text
Health Information
Services
Elsevier iConsult
Scientific Literature
PubMed300 Documents
Published Online each day
User-contributed Content (Informal)
GeneRifs
NCBI Public Datasets
Genome, Protein DBs
new sequencesdaily
Laboratory Data
Lab tests, RTPCR,
Mass spec
Clinical Data
Personal health history
Search, browsing, complex query, integration, workflow, analysis, hypothesis validation, decision support.
binary
Knowledge Enabled Information and Services Science
Scenario 1:
• Status: In use today
• Where: Athens Heart Center
• What: Use of semantic Web technologies for clinical decision support
Knowledge Enabled Information and Services Science
Operational since January 2006
Knowledge Enabled Information and Services Science
Goals:• Increase efficiency with decision support
• formulary, billing, reimbursement
• real time chart completion
• automated linking with billing
• Reduce Errors, Improve Patient Satisfaction & Reporting• drug interactions, allergy, insurance
• Improve Profitability
Technologies:• Ontologies, semantic annotations & rules
• Service Oriented Architecture
Thanks -- Dr. Agrawal, Dr. Wingeth, and others. ISWC2006 paper
Active Semantic Electronic Medical Records (ASEMR)
Knowledge Enabled Information and Services Science
Demonstration
Knowledge Enabled Information and Services Science
0
100
200
300
400
500
600
Month/Year
Ch
art
s
Same Day
Back Log
Chart Completion before the preliminary deployment
ASMER Efficiency
0100200300400500600700
Sept05
Nov 05 Jan 06 Mar 06
Month/Year
Ch
arts Same Day
Back Log
Chart Completion after the preliminary deployment
Knowledge Enabled Information and Services Science
Scenario 2:
• Status: Demonstration
• Where: W3C Health Care and Life Sciences (HCLS) interest group
• What: Using semantic web to aggregate and query data about Alzheimer’s
• http://www.w3.org/2001/sw/hcls/
Knowledge Enabled Information and Services Science
Scenario 2: Scientific Data Sets for Alzheimer’s
Knowledge Enabled Information and Services Science
SPARQL Query spanning multiple sources
Knowledge Enabled Information and Services Science
Scenario 3
• Status: Completed research• Where: NIH • What: Understanding the genetic basis of
nicotine dependence. Integrate gene and pathway information and show how three complex biological queries can be answered by the integrated knowledge base.
• How: Semantic Web technologies (especially RDF, OWL, and SPARQL) support information integration and make it easy to create semantic mashups (semantically integrated resources).
Knowledge Enabled Information and Services Science
Motivation
• NIDA study on nicotine dependency• List of candidate genes in humans• Analysis objectives include:
o Find interactions between geneso Identification of active genes – maximum
number of pathwayso Identification of genes based on anatomical
locations• Requires integration of genome and biological
pathway information
Knowledge Enabled Information and Services Science
Entrez Gene
ReactomeKEGG
HumanCyc
GeneOntology HomoloGene
Genome and pathway information integration
•pathway
•protein
•pmid
•pathway
•protein
•pmid •pathway
•protein
•pmid
•GO ID
•HomoloGene ID
Knowledge Enabled Information and Services Science
JBI
Knowledge Enabled Information and Services Science
BioPAXontology
EntrezKnowledge
Model(EKoM)
Knowledge Enabled Information and Services Science
Deductive Reasoning Protein-Protein Interaction RULE: given that two genes interact with each other, given certain number of parameters being met, we can assert that the gene products also interact with each other
IF (x have_common_pathway y) AND (x rdf:type gene) AND (y rdf:type gene) AND (x has_product m) AND (y has_product n) AND (m rdf:type gene_product)AND (n rdf:type gene_product) THEN (m ? n)
gene_product
gene_producthas_product
have
_com
mon
_pat
hway
gene2
gene1has_product
database_identifier 2associated_with
associated_withdatabase_identifier 1
inte
ract
s_w
ith
Knowledge Enabled Information and Services Science
Scenario 4
• Status: Completed research
• Where: NIH
• What: queries across integrated data sources– Enriching data with ontologies for integration,
querying, and automation– Ontologies beyond vocabularies: the power of
relationships
Knowledge Enabled Information and Services Science
Use data to test hypothesis
gene
GO
PubMed
Gene name
OMIM
Sequence
Interactions
Glycosyltransferase
Congenital muscular dystrophy
Link between glycosyltransferase activity and Link between glycosyltransferase activity and congenital muscular dystrophy?congenital muscular dystrophy?
Adapted from: Olivier Bodenreider, presentation at HCLS Workshop, WWW07
Knowledge Enabled Information and Services Science
In a Web pages world…
Congenital muscular dystrophy,
type 1D
(GeneID: 9215)
has_associated_disease
has_molecular_function
Acetylglucosaminyl-transferase activity
Adapted from: Olivier Bodenreider, presentation at HCLS Workshop, WWW07
Knowledge Enabled Information and Services Science
With the semantically enhanced data
MIM:608840Muscular dystrophy, congenital, type 1D
GO:0008375
has_associated_phenotype
has_molecular_function
EG:9215LARGE
acetylglucosaminyl-transferase
GO:0016757glycosyltransferase
GO:0008194isa
GO:0008375acetylglucosaminyl-
transferase
GO:0016758
From medinfo paper.Adapted from: Olivier Bodenreider, presentation at HCLS Workshop, WWW07
SELECT DISTINCT ?t ?g ?d { ?t is_a GO:0016757 . ?g has molecular function ?t . ?g has_associated_phenotype ?b2 . ?b2 has_textual_description ?d .FILTER (?d, “muscular distrophy”, “i”) . FILTER (?d, “congenital”, “i”) }
Knowledge Enabled Information and Services Science
Scenario 5
• Status: Research prototype and in progress• Workflow withSemantic Annotation of Experimental
Data already in use
• Where: UGA
• What:– Knowledge driven query formulation– Semantic Problem Solving Environment (PSE)
for Trypanosoma cruzi (Chagas Disease)
Knowledge Enabled Information and Services Science
Knowledge driven query formulation
Complex queries can also include:- on-the-fly Web services execution to retrieve additional data- inference rules to make implicit knowledge explicit
Knowledge Enabled Information and Services Science
T.Cruzi PSE Query Interface
Figure 4: Semantic annotation of ms scientific data
Knowledge Enabled Information and Services Science
N-GlycosylationN-Glycosylation ProcessProcess (NGPNGP)
Cell Culture
Glycoprotein Fraction
Glycopeptides Fraction
extract
Separation technique I
Glycopeptides Fraction
n*m
n
Signal integrationData correlation
Peptide Fraction
Peptide Fraction
ms data ms/ms data
ms peaklist ms/ms peaklist
Peptide listN-dimensional arrayGlycopeptide identificationand quantification
proteolysis
Separation technique II
PNGase
Mass spectrometry
Data reductionData reduction
Peptide identificationbinning
n
1
Knowledge Enabled Information and Services Science
Storage
Standard FormatData
Raw Data
Filtered Data
Search Results
Final Output
Agent Agent Agent Agent Biological Sample Analysis
by MS/MS
Raw Data to
Standard Format
DataPre-
process
DB Search
(Mascot/Sequest)
Results Post-
process
(ProValt)
O I O I O I O I O
Biological Information
SemanticAnnotationApplications
Semantic Web Process to incorporate provenance
Knowledge Enabled Information and Services Science
830.9570 194.9604 2
580.2985 0.3592
688.3214 0.2526
779.4759 38.4939
784.3607 21.7736
1543.7476 1.3822
1544.7595 2.9977
1562.8113 37.4790
1660.7776 476.5043
parent ion m/z
fragment ion m/z
ms/ms peaklist data
fragment ionabundance
parent ionabundance
parent ion charge
ProPreO: Ontology-mediated provenance
Mass Spectrometry (MS) Data
Knowledge Enabled Information and Services Science
<ms-ms_peak_list>
<parameter instrument=“micromass_QTOF_2_quadropole_time_of_flight_mass_spectrometer”
mode=“ms-ms”/>
<parent_ion m-z=“830.9570” abundance=“194.9604” z=“2”/>
<fragment_ion m-z=“580.2985” abundance=“0.3592”/>
<fragment_ion m-z=“688.3214” abundance=“0.2526”/>
<fragment_ion m-z=“779.4759” abundance=“38.4939”/>
<fragment_ion m-z=“784.3607” abundance=“21.7736”/>
<fragment_ion m-z=“1543.7476” abundance=“1.3822”/>
<fragment_ion m-z=“1544.7595” abundance=“2.9977”/>
<fragment_ion m-z=“1562.8113” abundance=“37.4790”/>
<fragment_ion m-z=“1660.7776” abundance=“476.5043”/>
</ms-ms_peak_list>
OntologicalConcepts
ProPreO: Ontology-mediated provenance
Semantically Annotated MS Data
Knowledge Enabled Information and Services Science
Scenario 6
• When: Research in progress
• Where: Athens Heart Center and Cincinatti Children’s Hospital Medical Center
• What: scientific literature mining– Dealing with unstructured information– Extracting knowledge from text– Complex entity recognition– Relationship extraction
Knowledge Enabled Information and Services Science
Heart Failure Clinical Pathway
causes
Disease
AngiotensionReceptor
Blocker (ARB)
Ontology: A Framework for Schema-Driven Relationship Discovery from Unstructured Text, Ramakrishnan, et. al., ISWC 2006, LNCS 4273, pp. 583-596
Knowledge Enabled Information and Services Science
Contextual delivery of information
Knowledge Enabled Information and Services Science
• Two technical challenges– Text mining– Workflow adaptation
Knowledge Enabled Information and Services Science
Diabetes mellitus adversely affects the outcomes in patients with myocardial infarction (MI), due in part to the exacerbation of left ventricular (LV) remodeling. Although angiotensin II type 1 receptor blocker (ARB) has been demonstrated to be effective in the treatment of heart failure, information about the potential benefits of ARB on advanced LV failure associated with diabetes is lacking. To induce diabetes, male mice were injected intraperitoneally with streptozotocin (200 mg/kg). At 2 weeks, anterior MI was created by ligating the left coronary artery. These animals received treatment with olmesartan (0.1 mg/kg/day; n = 50) or vehicle (n = 51) for 4 weeks. Diabetes worsened the survival and exaggerated echocardiographic LV dilatation and dysfunction in MI. Treatment of diabetic MI mice with olmesartan significantly improved the survival rate (42% versus 27%, P < 0.05) without affecting blood glucose, arterial blood pressure, or infarct size. It also attenuated LV dysfunction in diabetic MI. Likewise, olmesartan attenuated myocyte hypertrophy, interstitial fibrosis, and the number of apoptotic cells in the noninfarcted LV from diabetic MI. Post-MI LV remodeling and failure in diabetes were ameliorated by ARB, providing further evidence that angiotensin II plays a pivotal role in the exacerbated heart failure after diabetic MI.
ARB causes heart failure
Extracting the Relationship
Angiotensin II type 1 receptor blocker attenuates exacerbated left ventricular remodeling and failure in diabetes-associated myocardial infarction.,Matsusaka H, et. al.
Knowledge Enabled Information and Services Science
Problem – Extracting relationships between MeSH terms from PubMed
Biologically active substance
LipidDisease or Syndrome
affects
causes
affectscauses
complicates
Fish Oils Raynaud’s Disease???????
instance_of instance_of
UMLS Semantic Network
MeSH
PubMed9284 documents
4733 documents
5 documents
Knowledge Enabled Information and Services Science
Background knowledge used
• UMLS – A high level schema of the biomedical domain– 136 classes and 49 relationships– Synonyms of all relationship – using variant lookup
(tools from NLM)– 49 relationship + their synonyms = ~350 mostly verbs
• MeSH – 22,000+ topics organized as a forest of 16 trees– Used to query PubMed
• PubMed – Over 16 million abstract– Abstracts annotated with one or more MeSH terms
T147—effect T147—induce T147—etiology T147—cause T147—effecting T147—induced
Knowledge Enabled Information and Services Science
Method – Parse Sentences in PubMed
SS-Tagger (University of Tokyo)
SS-Parser (University of Tokyo)
(TOP (S (NP (NP (DT An) (JJ excessive) (ADJP (JJ endogenous) (CC or) (JJ exogenous) ) (NN stimulation) ) (PP (IN by) (NP (NN estrogen) ) ) ) (VP (VBZ induces) (NP (NP (JJ adenomatous) (NN hyperplasia) ) (PP (IN of) (NP (DT the) (NN endometrium) ) ) ) ) ) )
• Entities (MeSH terms) in sentences occur in modified forms• “adenomatous” modifies “hyperplasia”• “An excessive endogenous or exogenous stimulation” modifies “estrogen”
• Entities can also occur as composites of 2 or more other entities• “adenomatous hyperplasia” and “endometrium” occur as “adenomatous hyperplasia of the endometrium”
Knowledge Enabled Information and Services Science
Method – Identify entities and Relationships in Parse Tree
TOP
NP
VP
S
NPVBZ
induces
NPPP
NPINof
DTthe
NNendometrium
JJadenomatous
NNhyperplasia
NP PP
INby
NNestrogenDT
the
JJexcessive ADJP NN
stimulation
JJendogenous
JJexogenous
CCor
MeSHIDD004967MeSHIDD006965 MeSHIDD004717
UMLS ID
T147
ModifiersModified entitiesComposite Entities
Knowledge Enabled Information and Services Science
• What can we do with the extracted knowledge?
• Semantic browser demo
Knowledge Enabled Information and Services Science
PubMed
Complex Query
SupportingDocument setsretrieved
Migraine
Stress
Patient
affects
isaMagnesium
Calcium Channel Blockers
inhibit
Keyword query: Migraine[MH] + Magnesium[MH]
Evaluating hypotheses
Knowledge Enabled Information and Services Science
Workflow Adaptation: Why and How
• Volatile nature of execution environments– May have an impact on multiple activities/ tasks in the
workflow
• HF Pathway – New information about diseases, drugs becomes
available – Affects treatment plans, drug-drug interactions
• Need to incorporate the new knowledge into execution– capture the constraints and relationships between
different tasks activities
Knowledge Enabled Information and Services Science
Workflow Adaptation Why?
New knowledge abouttreatment found duringthe execution of the pathway
New knowledge about drugs,drug drug interactions
Knowledge Enabled Information and Services Science
Workflow Adaptation: How
• Decision theoretic approaches– Markov Decision Processes
• Given the state S of the workflow when an event E occurs– What is the optimal path to a goal state G– Greedy approaches rely on local optimization
• Need to choose actions based on optimality across the entire horizon, not just the current best action
– Model the horizon and use MDP to find the best path to a goal state
Knowledge Enabled Information and Services Science
Conclusion
• semantic web technologies can help with:– Fusion of data: semi-structured, structured,
experimental, literature, multimedia– Analysis and mining of data, extraction,
annotation, capture provenance of data through annotation, workflows with SWS
– Querying of data at different levels of granularity, complex queries, knowledge-driven query interface
– Perform inference across data sets
Knowledge Enabled Information and Services Science
Take home points
• Shift of paradigm: from browsing to querying
• Machine understanding: – extracting knowledge from text– Inference, software interoperation
• Semantic-enabled interfaces towards hypothesis validation
Knowledge Enabled Information and Services Science
References
1. A. Sheth, S. Agrawal, J. Lathem, N. Oldham, H. Wingate, P. Yadav, and K. Gallagher, Active Semantic Electronic Medical Record, Intl Semantic Web Conference, 2006.
2. Satya Sahoo, Olivier Bodenreider, Kelly Zeng, and Amit Sheth, An Experiment in Integrating Large Biomedical Knowledge Resources with RDF: Application to Associating Genotype and Phenotype Information WWW2007 HCLS Workshop, May 2007.
3. Satya S. Sahoo, Kelly Zeng, Olivier Bodenreider, and Amit Sheth, From "Glycosyltransferase to Congenital Muscular Dystrophy: Integrating Knowledge from NCBI Entrez Gene and the Gene Ontology, Amsterdam: IOS, August 2007, PMID: 17911917, pp. 1260-4
4. Satya S. Sahoo, Olivier Bodenreider, Joni L. Rutter, Karen J. Skinner , Amit P. Sheth, An ontology-driven semantic mash-up of gene and biological pathway information: Application to the domain of nicotine dependence, submitted, 2007.
5. Cartic Ramakrishnan, Krzysztof J. Kochut, and Amit Sheth, "A Framework for Schema-Driven Relationship Discovery from Unstructured Text", Intl Semantic Web Conference, 2006, pp. 583-596
6. Satya S. Sahoo, Christopher Thomas, Amit Sheth, William S. York, and Samir Tartir, "Knowledge Modeling and Its Application in Life Sciences: A Tale of Two Ontologies", 15th International World Wide Web Conference (WWW2006), Edinburgh, Scotland, May 23-26, 2006.
• Demos at: http://knoesis.wright.edu/library/demos/
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