Isaac “ Zak ” Kohane, MD, PhD From Bedside to Bench and Back.
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Transcript of Isaac “ Zak ” Kohane, MD, PhD From Bedside to Bench and Back.
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Isaac “Zak” Kohane, MD, PhD
From Bedside to Bench and Back
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First signal:• 1 year after
Celecoxib • 8 months
after Rofecoxib
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Oral Hypoglycemic Agents
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Without strong priors
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Major Modes of EHR Driven Genomic Research (EDGR)
EHR
EHR
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EDGR Advantages
• Timeliness• Clinical Relevance• Underserved populations• Controls• Co-morbidity recognition (e.g. PheWAS)
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Accrual Rates
Murphy et al Genome Research, 2009
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Costs
Murphy et al Genome Research, 2009
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Kurreeman, AJHG 2011But it works…
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Kurreeman, AJHG 2011
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Timeline
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EDGR Challenges
• Consent (None/Opt-in/Opt-Out)• Cost of EHRs• Quality of EHR data• Lack of Family History codification• Lack of EHR standardization• Cultural gulf between clinical informatics
and bioinformatics.– Translational Bioinformatics
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Application to a common pediatric disease
• With an understudied epidemiology
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Aggregating across 4 hospitals, 3 i2b2 instances
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Co-morbidities in autism vs. hospital population
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2012
SHRINE conf 6/29
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Thank you
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Challenge: Efficiently Reach Large N for Population studies
• High throughput genotyping• High throughput phenotyping• High throughput sample acquisition
DHHS Secretary’s Advisory Committee on Genetics, Health, and Society (SACGHS) argues for the health value of a 500,000 to 1M subject study. Estimated cost: $3,000,000,000
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Who?Health Care Utilization
(Hospitalization, ED Visits)
+
Genes
Clinical
Factors
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NLP (and comedy) is not pretty
HOSPITAL COURSE: ... It was recommended that she receive …We also added Lactinax, oral form of Lactobacillus acidophilus to attempt a repopulation of her gut.
SH: widow,lives alone,2 children,no tob/alcohol.
BRIEF RESUME OF HOSPITAL COURSE: 63 yo woman with COPD, 50 pack-yr tobacco (quit 3 wks ago), spinal stenosis, ...
SOCIAL HISTORY: Negative for tobacco, alcohol, and IV drug abuse.
SOCIAL HISTORY: The patient is a nonsmoker. No alcohol.
SOCIAL HISTORY: The patient is married with four grown daughters,uses tobacco, has wine with dinner.Smoker
Non-Smoker
SOCIAL HISTORY: The patient lives in rehab, married. Unclear smoking historyfrom the admission note…
Past Smoker
Hard to pick
Hard to pick
???
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Crimson: Core Functions
Clinical discardMined PhenotypesMatched
AnonymousID
Richly annotated biospecimens
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Free and Open Source Translational Toolkit: Implementations
DataRepository
(CRC)
FileRepository
IdentityManagement
OntologyManagement
Data Queries DataVisualization
CorrelationAnalysis
De -Identification
Of data
NaturalLanguageProcessing
AnnotatingGenomic
Data
ProjectManagement
WorkflowFramework
Visual TermMapping
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Major Modes (II)