From Bedside to Bench and Back
Isaac “Zak” Kohane, MD, PhD
i2b2
Informatics for Integrating Biology & the Bedside
A National Center for Biomedical Computing
i2b2
Informatics for Integrating Biology & the Bedside
First signal:
• 1 year after
Celecoxib
• 8 months
after
Rofecoxib
A National Center for Biomedical Computing
Oral Hypoglycemic Agents
i2b2
Informatics for Integrating Biology & the Bedside
A National Center for Biomedical Computing
Without strong priors
i2b2
Informatics for Integrating Biology & the Bedside
A National Center for Biomedical Computing
Major Modes of EHR Driven
Genomic Research (EDGR)
EHR
Genome-Scale
Measurements
EHR
i2b2
Informatics for Integrating Biology & the Bedside
Genome-Scale
Measurements
A National Center for Biomedical Computing
EDGR Advantages
•
•
•
•
•
Timeliness
Clinical Relevance
Underserved populations
Controls
Co-morbidity recognition (e.g. PheWAS)
i2b2
Informatics for Integrating Biology & the Bedside
A National Center for Biomedical Computing
i2b2
Informatics for Integrating Biology & the Bedside
Accrual Rates
Murphy et al Genome Research, 2009
A National Center for Biomedical Computing
i2b2
Informatics for Integrating Biology & the Bedside
Costs
Murphy et al Genome Research, 2009
A National Center for Biomedical Computing
But it works…
i2b2
Informatics for Integrating Biology & the Bedside
Kurreeman, AJHG 2011
A National Center for Biomedical Computing
i2b2
Informatics for Integrating Biology & the Bedside
Kurreeman, AJHG 2011
A National Center for Biomedical Computing
i2b2
Informatics for Integrating Biology & the Bedside
Timeline
A National Center for Biomedical Computing
i2b2
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
Informatics for Integrating Biology & the Bedside
A National Center for Biomedical Computing
Application to a common
pediatric disease
• With an understudied epidemiology
i2b2
Informatics for Integrating Biology & the Bedside
A National Center for Biomedical Computing
Aggregating across 4 hospitals, 3
i2b2 instances
i2b2
Informatics for Integrating Biology & the Bedside
A National Center for Biomedical Computing
i2b2
Informatics for Integrating Biology & the Bedside
A National Center for Biomedical Computing
Co-morbidities in autism vs.
hospital population
19.17%
25.00%
All Pa ents
i2b2
Informatics for Integrating Biology & the Bedside
ne
Au
to
im
mu
s
ep
Sl e
DM
A National Center for Biomedical Computing
dis
or
d
(ty
pe
er
1)
s
er
so
rd
Di
Bo
we
l
izo
Sc
h
IBD
nia
ph
re
ps
y
ile
Ep
CN
S/
He
ad
An
om
ali
es
0.00%
0.68%
0.67%
0.14%
0.34%
0.79%
4.50%
0.54%
0.83%
0.24%
5.00%
2.43%
2.41%
10.00%
2.85%
6.40%
15.00%
1.12%
11.74%
20.00%
ASD
i2b2
Informatics for Integrating Biology & the Bedside
2012
SHRINE conf 6/29
A National Center for Biomedical Computing
i2b2
Informatics for Integrating Biology & the Bedside
Thank you
A National Center for Biomedical Computing
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
i2b2
Informatics for Integrating Biology & the Bedside
A National Center for Biomedical Computing
Genes
+
Who?
Health Care Utilization
(Hospitalization, ED Visits)
Clinica
l
Factor
s
i2b2
Informatics for Integrating Biology & the Bedside
A National Center for Biomedical Computing
NLP (and comedy) is not pretty
SOCIAL HISTORY: The patient is married with four grown daughters,
Smoker
uses tobacco, has wine with dinner.
SOCIAL HISTORY: The patient is a nonsmoker. No alcohol.
Non-Smoker
SOCIAL HISTORY: Negative for tobacco, alcohol, and IV drug abuse.
BRIEF RESUME OF HOSPITAL COURSE:
Past
Smoker
63 yo woman with COPD, 50 pack-yr tobacco (quit 3 wks ago), spinal
stenosis,
...
SOCIAL HISTORY: The patient lives in rehab, married. Unclear smoking history
from the admission note…
???
HOSPITAL COURSE: ... It was recommended that she receive …We also added Lactinax, oral
form of Lactobacillus acidophilus
to attempt
a repopulation of her gut.
Hard
to pick
SH: widow,lives alone,2 children,no tob/alcohol.
i2b2
Informatics for Integrating Biology & the Bedside
A National Center for Biomedical Computing
Hard to pick
Crimson: Core Functions
Mined Phenotypes
i2b2
Informatics for Integrating Biology & the Bedside
Matched
Anonymous
ID
Richly annotated biospecimens
A National Center for Biomedical Computing
Clinical discard
Free and Open Source Translational
Toolkit: Implementations
Natural
Language
Processing
Project
Management
Visual Term
Mapping
Ontology
Management
Annotating
Genomic
Data
i2b2
Informatics for Integrating Biology & the Bedside
De Identification
Of data
File
Repository
Identity
Management
Data
Repository
(CRC)
Workflow
Framework
Data
Visualization
Data Queries
Correlation
Analysis
A National Center for Biomedical Computing
i2b2
Informatics for Integrating Biology & the Bedside
Major Modes (II)
A National Center for Biomedical Computing