By: Joel Dudley, Mount Sinai School of Medicine At Sherbrooke International Life Sciences Summit - 2nd edition | September 28/29/30 2015 www.sils-sherbrooke.com

1. Connecting Precision Medicine
to Precision Wellness towards a
systems understanding of
health and disease
Joel Dudley, PhD
Director of Biomedical Informatics &
Associate Professor of Genetics and Genomic
Sciences, Icahn School of Medicine at Mount Sinai
Icahn School of Medicine at
Mount Sinai @IcahnInstitute

2. Mount Sinai Health System
>6,000
Physicians
7
Member hospital campuses
>3,500
>3,100,000
Patient visits
Hospital beds

3. “The future is already here — it's
just not very evenly distributed”.
- William Gibson

4. There are rarely smoking guns in
human health

5. There are rarely smoking guns in
human health

6. No such thing as a “simple” disease
Cutting GR. Nature Reviews Genetics. (2014) doi:10.1038/nrg3849
Woody Guthrie

7. Complex molecular networks underlie
human physiology

8. We must embrace complexity to fully
understand patient physiology and disease
“A complex adaptive system has three characteristics.
The first is that the system consists of a number of
heterogeneous agents, and each of those agents makes
decisions about how to behave. The most important
dimension here is that those decisions will evolve over
time. The second characteristic is that the agents
interact with one another. That interaction leads to the
third—something that scientists call emergence: In a
very real way, the whole becomes greater than the sum
of the parts. The key issue is that you can’t really
understand the whole system by simply looking at its
individual parts”.
- Michael J. Mauboussin (investment banker)

10. Icahn Institute for Genomics and Multiscale Biology

11. Being masters of really big data is now critical
for biomedical research (TB→PB→EB→ZB)
Organisms Tissues Single cells
Single cell,
real-time,
continuous?

12. Biology’s atom smasher moment— We can
measure more than we know

13. Redefining the system of human disease with data
~300 Diseases
and Conditions
20k+ Genes
Blue: gene goes
down in disease
Yellow: gene goes up
in disease

14. Redefining the system of human disease with data
Suthram S, Dudley J et al. Network-based elucidation of human disease similarities reveals common functional
modules enriched for pluripotent drug targets. PLoS Computational Biology (2010)
Figure 2. Significant disease-disease similarities. (A)Hierarchical clustering of thediseasecorrelations.Thedistancebetweentwo disease
defined to be(1-correlation coefficient) of thetwo diseases. Thetree wasconstructed using theaverage method of hierarchical clustering. Th
line corresponds to a p-value of 0.01 and FDRof 10.37%and, disease correlations below this line are considered significant. The different c

15. Unexpected connection: anticonvulsant drug treats
inflammatory bowel disease
• TNBS chemically
induced rat model of
IBD
• Animals treated with
80mg/kg topiramate
oral after
sensitization
• Prednisolone positive
control (approved for
IBD in humans)
Dudley, J. T., Sirota, M., et al. (2011). Computational Repositioning of the Anticonvulsant Topiramate for
Inflammatory Bowel Disease. Science Translational Medicine, 3(96).

16. Control Imipramine
Unexpected connection: antipsychotic drug treats small cell
lung cancer
p53/Rb/p130
triple knockout
model of SCLC
Mice dosed
after
tumor
formation

17. Kidd BA, Wroblewska A, Agudo J, Merad M, Brown BD, Dudley JT. Systematic integrative analysis of immune pharmacology. (2015)
Nature Biotechnology. in press.
How do approved drugs modulate networks
in immune cells?

18. Antifungal activates neutrophil migration
Drug A
Drug B
Drug A
Drug A Drug B
Drug A Drug B
Drug A Drug B
Kidd BA, Wroblewska A, Agudo J, Merad M, Brown BD, Dudley JT. Systematic integrative analysis of
immune pharmacology. (2015) Nature Biotechnology. in press.

19. Antifungal activates neutrophil migration
Drug A
Drug B
Drug A
Drug A Drug B
Drug A Drug B
Drug A Drug B
Kidd BA, Wroblewska A, Agudo J, Merad M, Brown BD, Dudley JT. Systematic integrative
analysis of immune pharmacology. (2015) Nature Biotechnology. in press.

20. Immunemod score predicts immune cell
perturbations in patient populations
Kidd BA, Wroblewska A, Agudo J, Merad M, Brown BD, Dudley JT. Systematic integrative analysis of immune pharmacology. (2015)
Nature Biotechnology. in press.

21. Understanding the multiscale complexity of
patient populations
=
Genomic
Environment
Clinical

22. Capturing rich multi scale data on patients
through the Mount Sinai Biobank

24. Image credit:
Li Li (ISMMS)

25. Type 2, Type 3, and Type 4 diabetes?

26. 200
Data Feeds
5Gb
Data/lap

27. 300
Sensors
3,000
Variables/0.1 sec
>200Gb
Data/day

29. We are on the crest of a tsunami in consumer
sensor technologies

30. Printable tattoo biosensor

34. Genome function is very context dependent
• eQTL
• What?
• Where?
• When?

35. Genome function is all about
context

36. Genome function is all about context

39. 1. Drug A
2. Drug B
3. Drug C
4. Tolfenamic Acid
5. Drug D
6. Drug E
7. …
SP1
NDMN Network Model
Drugs perturbing SP1 sub-
network towards healthy
prioritized by network activity
The network as the target

40. Web-scale deep computing as the future of
medicine and research
http://www.bbc.com/news/technology-18595351

41. Web-scale deep computing as the future of
medicine and research
Xiong et al. Science 9 January 2015

42. Consumer health
tools as a driver
of data-driven
healthcare
Where will most
of the health
data be in 5-10
years?

43. We can embrace digital health and sensors to map the
human phoneme and envirome

44. Electronic Consent and Patient Engagement

45. Electronic Consent and Patient Engagement

46. A Learning Digital Health Platform for Chronic
Lung Disease

47. A Learning Digital Health Platform for Chronic
Lung Disease

48. We need to collect “long” dynamic data
for Precision Wellness

49. In the future you will have coordinates instead of a diagnosis
Topol EJ. Individualized Medicine from Prewomb to Tomb Cell 157, March 27, 2014

50. The emergence of science- and data-driven wellness
info@precisionwellness.org

51. The emergence of science- and data-driven wellness
info@precisionwellness.org
Digital Health
Molecular Profiling
Data Science
Clinical Medicine
The Harris Center for Precision Wellness
www.precisionwellness.org

53. “The future is already here — it's
just not very evenly distributed”.
- William Gibson

54. Email: joel.dudley@mssm.edu
Twitter: @jdudley
Web: dudleylab.org
precisionwellness.org
Icahn School of Medicine at
Mount Sinai
Thank you for your attention!