obtaining the numbers behind the translational imperative harvard medical school center for...
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i2b2 A National Center for Biomedical ComputingInformatics for Integrating Biology & the Bedside
Obtaining The Numbers Behind the Translational Imperative
Harvard Medical School
Center for Biomedical Informatics
i2b2 National Center for Biomedical ComputingIsaac S. Kohane, MD, PhD
John Glaser, PhD
Susanne Churchill, PhD
i2b2 A National Center for Biomedical ComputingInformatics for Integrating Biology & the Bedside
Example: PPAR Pro12Ala and diabetes
0.10.20.30.40.50.60.70.80.911.11.2Estimated risk
(Ala allele) 1.32.0
Deeb et al.Mancini et al.
Ringel et al.
Meirhaeghe et al.
Clement et al.
Hara et al.
Altshuler et al.
Hegele et al.
Oh et al.
Douglas et al.
All studies
Lei et al.Hasstedt et al.
1.41.51.61.71.81.9
Sample size
Ala is protective
Mori et al.
Overall P value = 2 x 10-7
Odds ratio = 0.79 (0.72-0.86)
Courtesy J. Hirschhorn
i2b2 A National Center for Biomedical ComputingInformatics for Integrating Biology & the Bedside
And here comes commercialization (MD’s not required)
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Knome has launched the first commercial whole-genome sequencing and analysis service for individuals for $350,000 per genome. The sequence data will undergo comprehensive analysis from a team of….
i2b2 A National Center for Biomedical ComputingInformatics for Integrating Biology & the Bedside
Common-Rare:Weak-Strong Spectrum
commonrare
108
patients
106 patients
102
diseases104
diseases
Deterministic“highly penetrant”
Weak effect, not predictive, dominated by environment
Huntington’s
Tay-Sachs
DM2
ASD
CAD
MODY
i2b2 A National Center for Biomedical ComputingInformatics for Integrating Biology & the Bedside
Dangers of Large N and small p(D)
i2b2 A National Center for Biomedical ComputingInformatics for Integrating Biology & the Bedside
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i2b2 A National Center for Biomedical ComputingInformatics for Integrating Biology & the Bedside
Challenge: Efficiently Reach Large N
• 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
Cost of the pediatric 100,000 study recently launched >> $1B + decades.
i2b2 A National Center for Biomedical ComputingInformatics for Integrating Biology & the Bedside
i2b2 A National Center for Biomedical ComputingInformatics for Integrating Biology & the Bedside
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
???
i2b2 A National Center for Biomedical ComputingInformatics for Integrating Biology & the Bedside
But it works
• 96,000 asthma patients identified out of 2.5M PHS patients– Stratified by severity, pharmaco-responsiveness
and exposures– Now with cases and controls (from extrema)
reconsented and biomaterials obtained for genome-wide scans ++
– 3 methods of tissue acquisition
i2b2 A National Center for Biomedical ComputingInformatics for Integrating Biology & the Bedside
The three prongs of High Throughput Instrumentation
• $250-$500 for 500,000 SNP’s• $50-100K for good quality phenotyping of 100K+
+ individuals• What about the samples (consented)
– $650/patient• Dozens a week
– Wait in clinic: $450+/patient
• Crimson– Lynn Bry, MD
i2b2 A National Center for Biomedical ComputingInformatics for Integrating Biology & the Bedside
Crimson: Core Functions
Clinical discardMined PhenotypesMatched
AnonymousID
Richly annotated biospecimens
i2b2 A National Center for Biomedical ComputingInformatics for Integrating Biology & the Bedside
Meeting Expectations
i2b2 A National Center for Biomedical ComputingInformatics for Integrating Biology & the Bedside
Accrual Rates
i2b2 A National Center for Biomedical ComputingInformatics for Integrating Biology & the Bedside
Costs
i2b2 A National Center for Biomedical ComputingInformatics for Integrating Biology & the Bedside
Thank you