stanford center for biomedical informatics research representing, querying and mining knowledge...
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Stanford Centerfor Biomedical Informatics Research
Representing, Querying and Mining Knowledge about Autism Phenotypes
Amar K. Das, MD, PhDDepartments of Medicine and
of Psychiatry and Behavioral Sciences
NDAR Ontology SIGJune 28, 2010
Outline Prior work NDAR project Phenologue project Future directions
NDAR Ontology SIGJune 28, 2010
Hasler G,et al. Toward constructing an endophenotype strategy for bipolar disorders. Biological Psychiatry (2006)
Represent findings and their links using structured knowledge
NDAR Ontology SIGJune 28, 2010
Phenomics
“A primary task for the new field of phenomics will be to clarify what, in practical terms, constitutes a phenotype and then to delineate the different phenotypic components that compose the phenome.”
Freimer & Sabatti, Nature Genetics (2003)
NDAR Ontology SIGJune 28, 2010
Phenotypes in Psychiatry
‘The observable structural and functional characteristics of an organism determined by its genotype and modulated by its environment’
Diagnostic component Intermediate phenotype Quantitative phenotype Covariates
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OMIM
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dbGaP
Mailman, M.D. Nature Genetics (2007)
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PhenoWiki
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PhenoWiki
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Current Approaches Lack of standardization Lack of organization Lack of computability
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NDAR Project Systematic review Extension to NIFSTD ontology Rulebase development
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Systematic Review “(ADI-R or ADOS or Vineland) and
(genes or genetics) and autism” 26/43 papers relevant
156 unique phenotypes found Mean # phenotypes 4.1, range 0-13 Three basic types (1:1, sum, cutoff score)
NDAR Ontology SIGJune 28, 2010
Systematic Review Different terms
e.g., ‘age of first phrases’ and ‘age of onset of phrase speech’
Different cutoff scorese.g., ‘delayed word’
Different definitionse.g., ‘regression’e.g., use of different instruments
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SWRL: Semantic Web Rule Language Rules in SWRL can be used to deduce
new knowledge about an existing OWL ontology
Specification can be extended through the use of built ins
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NDAR Codebook
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Extension to NIFSTD
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Phenologue Project (R01 MH877)
Develop a knowledge base that maps phenotypes to brain connectivity, neural deficits, and genetic markers
Develop logic-based methods to encode and classify phenotypes based on multi-scale measurements
Create tools to acquire new phenotypes and annotate phenotype-genotype findings in online resources such as published literature
Develop query-elicitation methods that can evaluate hypotheses about the phenotypes using deductive inference
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Phenologue Project
Database
Phenotype Definitions
New Associations
Query
Catalog Analysis
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Axiomé Rule Management Tool Rule paraphrasing Rule elicitation Rulebase visualization Knowledge mining using rules
Hassanpour. S., et al. RuleML (2009)
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Computational Phenomics Develop methods to
Apply machine learning methods to discover groups of rules with common semantics
Use natural language processing method to discover phenotype rules in published text
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Semantic Similarity
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Semantic Clustering Use vector space model and k-
means clustering
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Semantic Clustering Found 17 phenotype clusters Example cluster
ConcludePositiveHistoryofRegressionConcludeNegativeHistoryofRegressionConcludeQuestionableHistoryofRegression1ConcludePositiveHistoryofRegression2ConcludePositiveHistoryofRegression1ConcludeQuestionableHistoryofRegression2ConcludeNoPhrasesConcludePhrasesConcludeNegativeHistoryofRegression
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Text Mining
Hassanpour. S., et al. ACM IHI (submitted)
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Evaluation of Precision
Level of Semantics Precision
Only rules 62%
Only ontology hierarchies 73%
Both rules and ontology hierarchies 76%
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Future Directions Develop rule management
technologies to support grouping Expand ontology to capture multi-
scale representation of endophenotypes