The Isaacus -Digital Health HUB closing event 1.11.2018 Ali Torkamani, Ph.D. Director of Genomics and Genome Informatics Scripps Research Translational Institute "Opportunities and Challenges for Genomics in Individualized Medicine"

1. Opportunities and Challenges for Genomics
in Individualized Medicine
Well-Being Data: Happy Birthday, Isaacus Rothovius
Ali Torkamani, Ph.D.
Director of Genomics and Genome Informatics
Scripps Research Translational Institute
Associate Professor, Integrative Structural and Computational Biology
Scripps Research
atorkama@scripps.edu
@ATorkamani

2. Disclosures
I am a shareholder of Human Longevity Inc.
I receive grant support from the National Institute of Health.

3. Genomics has and will continue to accelerate:
Disease Prevention, Detection, and Treatment
Genomic Risk Factors Traditional Risk Factors

4. Disease
Prevention
Genetic Risk
Factors
Clinical Risk
Factors

5. Monogenic Risk
+ = Dx*
Opportunity: Phenotype First i.e. diagnosis of overt disease,
or clarification of familial risk
*Diagnostic Yield Variable ~30% - 60%

6. Example:
Phenotype to Genotype in 19.5 hours
Opportunity: Early and Targeted Interventions

7. Monogenic Risk
+ =
Challenge: Genotype First i.e. health risk in healthy people
Disease Susceptibility

8. Example:
BRCA2 and Mammography, Mastectomy, or Oophorectomy?
Rebbeck et al., JAMA 2015
Intensive
Screening
Invasive
Intervention
Challenge: specific + quantitative risk required to best inform health decision making.
Location of Risk
Degree of Risk

9. Polygenic Risk
Design
100,000+ subjects
Results
Millions of known variants
Polygenic Risk Score
Cumulative sum
w/ Trait w/o Trait
Σ

10. Opportunity:
Polygenic Risk is Actionable
Torkamani et al., Nat. Rev Genet. 2018
Statin treated
MI prevented
Screened
Cancer detected
PSA False positive
PSA True positive

11. Challenge:
Driving and Prioritizing Behavior Change
Image from Myriad Genetics
Low risk?
?Less frequent screening?
Target lifestyle risks?
High risk

12. Challenge:
How to Deliver, Store, and Use Polygenic Risk
Direct to Consumer Providers / Payors Public Policy

13. Your Genome, On Demand
Ali T’s Health
Challenge: Deliver Information at time of Health Decision Making

14. Disease
Detection

15. Non-Invasive Prenatal Screening
Image: NHGRI

16. Circulating Tumor DNA
Image: Bettegowda et al., Science Translational Medicine 2014

17. Opportunity + Challenge:
Circulating Nucleotides
Image: De Vlaminck et al., Science Translational Medicine 2014

18. Increased utility through…
Integration with Health Data
Torkamani et al., Cell 2017
Risk-Informed
Action Threshold

19. Genomics as a part of… High Definition Medicine
Torkamani et al., Cell 2017

20. Acknowledgements
Kristian Andersen PhD
Will Liu
Bhuvan Molparia PhD
Evan Muse MD PhD
Manuel Rueda PhD
Amalio Telenti MD PhD
Brian Schrader
Emily Spencer PhD
Eric Topol MD
Nathan Wineinger PhD
Paris Zhang
Contact:
atorkama@scripps.edu
@ATorkamani
NIH/NCRR flagship CTSA Grant
Gary and Mary West Foundation
Lavin Family Foundation
Leducq Foundation
Stowers Family Foundation
BD2K U54GM114833
Funding