NEUROWEB: Modeling cerebrovascular phenotypes Gianluca Colombo Daniele Merico DISCo, Università di Milano- Bicocca SSW09 Signs, Symptoms and Findings: Towards an Ontology for Clinical Phenotypes. Milan, 4-5 September 2009 European Commission Sixth Framework Programme Information Society Technologies project number 518513 NEUROWEB Project
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NEUROWEB: Modeling cerebrovascular phenotypes Gianluca Colombo Daniele Merico DISCo, Università di Milano-Bicocca SSW09 Signs, Symptoms and Findings: Towards.
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NEUROWEB:Modeling cerebrovascular phenotypes
Gianluca ColomboDaniele Merico
DISCo, Università di Milano-Bicocca
SSW09Signs, Symptoms and Findings:
Towards an Ontology for Clinical Phenotypes.
Milan, 4-5 September 2009
European CommissionSixth Framework Programme
Information Society Technologies project number 518513
NEUROWEB Project
Act IAssociation Studies
and Clinical Phenotypes
Association Studies
1. Identify patients with a common (clinical) phenotype
2. Determine the statistical significance of association for– Genotype (i.e. Single Nucleotide Polymorphisms)– Environmental / life style factors– Etc…
Other patients
Phenotype carriers(e.g. Severe Stenosis)
SNP S1
SNP S2
SNP S3
Genotype
Prosthetic Heart Valve
Smoked Cigarettes
Clinical Features and Risk Factors
Blood Pressure
Clinical Phenotype(Association Studies)
• Of clinical interest, i.e. typically encountered as an intermediate or final stage of diagnosis, or treatment formulation, or prognosis
• Clinically abnormal sensu OGMS(?)– Not in the body plan
– Potentially resulting in pain / malaise / dysfunction / death
Clinical Phenotype(Association Studies)
• An aggregate of ‘bodily features’ (sensu OGMS) – directly observabledirectly observable (e.g. brain lesion)
or derived / inferablederived / inferable (e.g Diabetes Mellitus Type-II)– which is likely to be strongly associated to
• A genotype, i.e. set of genomic positions with nucleotide value(s)
• A (set of) physiological parameter (e.g. blood pressure)
• A (set of) environmental or life style factor (e.g. cholesterol-rich diet)
• Aggregation rationale: – StrengthStrength of association
– ParsimonyParsimony of associated factorsgenotype-phenotype
• Mutation in a single gene (strictly mendelian)• Multigenic (but maybe belonging to a certain functional category or pathway)
Hypothesis formulation and testing cycles
• NB: AssociationNB: Association may (or may not) imply causationcausation
Etio-physiological relatednessof aggregated bodily features
• Generating queries and accessing local repositories requires two tasks: – The elements of the local
repository need to be mapped into the ones in the Reference Ontology and the CDS (N2L);
– The NEUROWEB phenotypes need to be transformed in queries in terms of the reference ontology elements that map to the local repository (Phenotype Converter).
• The net effect is the translation of high-level concepts into regular SQL queries.
Reasoner(Jena)
N2LConverter
N2LConverter
DB1
PhenotypeConverter
User2
NWInterface
User1
Mediator Mediator
Queries rewriter
OntologyT-Box
QueryEngine
DB2
QueryEngine
• Querying the Ontology (Top Phenotypes) the NW Ontology engine returns portions of the Ontology graph of interest for clinicians w.r.t.:– DBs Analysis (NW
Ontology Engine)
SPQRLqueries
NWOntology engine
Mediator
NW Ontology Engine Services
NWGenomic engine
• Querying the Ontology the NW Ontology engine returns portions of the Ontology graph of interest for clinicians w.r.t.:– DBs Analysis:
• Evaluation of the methodological coherence of the federated data bases according to their compliancy to the NW Ontology (exploiting the Low Phenotype layer, i.e. the Composite Evidences Sub-Layer);
NW Ontology Engine Services
CDS
Top Phenotype
Composite Evidences
Low Phenotype
Atomic Evidences
DerivedEvidences
DBsRecords
Reasoner(Jena)
N2LConverter
N2LConverter
DB1
PhenotypeConverter
User2
NWInterface
User1
Mediator Mediator
Queries rewriter
OntologyT-Box
QueryEngine
DB2
QueryEngine
• Querying the Ontology the NW Ontology engine returns portions of the Ontology graph of interest for clinicians w.r.t.:– Genomic Analysis (NW
Genomic Engine)
SPQRLqueries
NWOntology engine
Mediator
NW Ontology Engine Services
NWGenomic engine
• Querying the Ontology (built-in queries) the NW Ontology engine returns portions of the Ontology graph of interest for clinicians w.r.t.:
– Genomic Analysis:• Evaluating two different
phenotypes associated with a common SNP, which may have a direct causative role in phenotype determination;