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2
Hacking the Software for Life
Brad Perkins, MD
Chief Medical Officer
Human Longevity, Inc.
@BradleyAPerkins
CONFIDENTIAL
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3
CONFIDENTIAL
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4
Four Trends Converge
To predict everything that can be
predicted from the human whole
genome sequence.
CONFIDENTIAL
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6
Merging Genotype with Phenotype Data
to Interpret Our Genetic Code
BIOLOGICAL DATA
INSIGHTS AND OUTCOMES
Genomics Phenotype
Computation
Diagnostics
& Therapies
Medical Care
Models
Machine
Learning
CONFIDENTIAL
NOT FOR DISTRIBUTION
7
• Uncovered 150 million new single
nucleotide genetic variants (SNVs),
82 million of which were novel
• Each sequenced genome contributed
more than 8,500 novel variants
• Using billions of data points, the team
mapped the invariant sites in the
genome
CONFIDENTIAL
NOT FOR DISTRIBUTION
8
Single Gene (Mendelian) and Genome-Wide
Association Studies (GWAS)
5% to 10% of all
cancers result from
inherited
single gene defects
• Cancers occurring at younger ages than usual
• Uncommon types of cancer
• More than one type of cancer in a single person
• More than one childhood cancer in a set of siblings
• Multiple common genetic variants contribute to risk
• Size effects are comparable to environmental factors
(e.g. 2-5 fold)
• Strong support from GWAS on tens of thousands of
individuals
Heritable Cancer (Mendelian): Mechanistic
Common Cancers (GWAS): Epidemiologic
Cancer
Risk
CONFIDENTIAL
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9
Human Microbiome: Early But Provocative Data
•Diabetes, Type 2
•Cardiovascular disease
•Cancer
•Inflammatory Bowel Disease
•Non-Alcoholic Fatty Liver Disease
(NAFLD)
•Obesity
•Autoimmune disorders
•Autism
1.77m 1.76m
MM
35y 38y
76kg82kg
PredictionSubject
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11
CONFIDENTIAL
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12
CONFIDENTIAL
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13
Age-Related Diseases are Leading Causes of
Pre-Mature Mortality in US Adults, 50-74 years
* Ages 50 – 74, 2013 in USA; Adapted from Institute of Health Metrics and Evaluation, University of Washington.
http://www.healthdata.org/results/data-visualizations
MALE
30%
RISK OF DEATH*
CARDIOVASCULAR
32%
CANCER
36%
FEMALE
20%
RISK OF DEATH*
CANCER
40%
CARDIOVASCULAR
25%
NEUROLOGIC
3%
CIRRHOSIS
3%
DIABETES
6%
RESPIRATORY
7%
OTHER
13%
RESPIRATORY
10%
DIABETES
10%
CIRRHOSIS
5%
NEUROLOGIC
5%OTHER
5%
CONFIDENTIAL
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14
Approaches to Curative and Preventive Medicine
Curative Preventive
Identify pathology Identify risk
Restore health Decrease risk
Promote individual
service ethic
Responsibility is to the
population
Clinical intervention
predominates
Behavioral and social
interventions are
prominent, accompanied by
clinical interventions
Fineberg H. JAMA 2013; 310(1):85-90
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15
Health Nucleus: PROACTIVE Curative AND
Preventive Medicine
PROACTIVE Curative AND Preventive
Identify pathology and risk
Restore health and decrease risk
Promote individual (and family/community) service ethic
Clinical, behavioral, and social interventions
CONFIDENTIAL
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16
Multi-Modality Data Gathering
Genomics Sciences, Historical Context, Quantitative Testing
 Whole-genome (30x)
 Microbiome
 Metabolomics
 Family & Med Hx
 Social
 Environmental
 Nutrition/Exercise
 Advanced Imaging (full
body MRI, Coronary CT)
 Multi-Functional Testing
 Exhaustive Labs
CONFIDENTIAL
NOT FOR DISTRIBUTION
17
HEALTH NUCLE I CASE STUDY
150GB
OVER AN 8 HOUR DAY
Collected
Heath Data
(6-8 hr visit)
1. WHOLE BODY
• MRI (Musculoskeletal/
Lipid Analysis)
• MRI (Organ Specific
RSI)
• DEXA Scan
• In Body Biometrics
• Over 70 Laboratory
Diagnostic Tests
• 3D Forensic Imaging
2. SEQUENCING
• Whole Genome
• Metabolome
• Microbiome
3. BRAIN
• NeuroQuant® Brain MRI
• 3D T2 Brain MRI
• Diffusion MRI
• Neurocognitive Testing
• Quant. Gait Analysis
4. PULMONOLOGY
• Pulmonary Function
• Testing
5. CARDIO-Vascular
• Echo (2D, 3D, 4D)
• ECG
• CT Scan (Coronary
Calcium Scoring)
• 2 Week Ambulatory
Rhythm Testing
2
1
3
4
5
CONFIDENTIAL
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18
HEALTH NUCLE I CASE STUDY
Fully-Automated,
PACS-Integrated,
Volumetric MRI
Alzheimer’sNormal
HEALTH NUCLE I CASE STUDY
CONFIDENTIAL
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19
Magnetic Resonance-Based Restricted Spectrum
Imaging for Early Cancer Detection
Cellularity Index
Nathan S. White et al. Cancer Res 2014;74:4638-4652
restricted
Time1/2
Displacement
RSI Model
Time
10 ms 20 ms 60 ms
CONFIDENTIAL
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20
HEALTH NUCLE I CASE STUDY
A DYNAMIC EXPERIENCE
THAT ALLOWS YOU TO
EXPLORE YOUR HEALTH
• Review your report with
you and your physician
• Develop a personalized
healthcare strategy
• Personal avatar and
healthcare record
The Living
Avatar Report
CONFIDENTIAL
NOT FOR DISTRIBUTION
21
Genomic & Phenotype Findings to Identify
Disease & Predict Risk (n=209)
Cardiovascular
Genomic Risk
Mendelian GWAS*
20 (10%) 79 (38%)
Cancer
Phenotype
Findings
151 (72%)
78 (37%)3 (1%) 5 (2%)
Metabolic
Neurodegenerative
27 (13%) 24 (11%) 91 (44%)
11 (5%) 26 (12%) 4 (2%)
*Genome-Wide Association Study
Other 64 (31%) 95 (46%) 6 (3%)
CONFIDENTIAL
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22
Medicine has been a clinical science,
supported by data.
Medicine is about to become a data science,
supported by clinicians.
CONFIDENTIAL
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2323
PRESENTED TO
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"Hacking the Software for Life" - Brad Perkins (Chief Medical Officer, Human Logevity, Inc.)

  • 2. CONFIDENTIAL NOT FOR DISTRIBUTION 2 Hacking the Software for Life Brad Perkins, MD Chief Medical Officer Human Longevity, Inc. @BradleyAPerkins
  • 5. To predict everything that can be predicted from the human whole genome sequence.
  • 6. CONFIDENTIAL NOT FOR DISTRIBUTION 6 Merging Genotype with Phenotype Data to Interpret Our Genetic Code BIOLOGICAL DATA INSIGHTS AND OUTCOMES Genomics Phenotype Computation Diagnostics & Therapies Medical Care Models Machine Learning
  • 7. CONFIDENTIAL NOT FOR DISTRIBUTION 7 • Uncovered 150 million new single nucleotide genetic variants (SNVs), 82 million of which were novel • Each sequenced genome contributed more than 8,500 novel variants • Using billions of data points, the team mapped the invariant sites in the genome
  • 8. CONFIDENTIAL NOT FOR DISTRIBUTION 8 Single Gene (Mendelian) and Genome-Wide Association Studies (GWAS) 5% to 10% of all cancers result from inherited single gene defects • Cancers occurring at younger ages than usual • Uncommon types of cancer • More than one type of cancer in a single person • More than one childhood cancer in a set of siblings • Multiple common genetic variants contribute to risk • Size effects are comparable to environmental factors (e.g. 2-5 fold) • Strong support from GWAS on tens of thousands of individuals Heritable Cancer (Mendelian): Mechanistic Common Cancers (GWAS): Epidemiologic Cancer Risk
  • 9. CONFIDENTIAL NOT FOR DISTRIBUTION 9 Human Microbiome: Early But Provocative Data •Diabetes, Type 2 •Cardiovascular disease •Cancer •Inflammatory Bowel Disease •Non-Alcoholic Fatty Liver Disease (NAFLD) •Obesity •Autoimmune disorders •Autism
  • 13. CONFIDENTIAL NOT FOR DISTRIBUTION 13 Age-Related Diseases are Leading Causes of Pre-Mature Mortality in US Adults, 50-74 years * Ages 50 – 74, 2013 in USA; Adapted from Institute of Health Metrics and Evaluation, University of Washington. http://www.healthdata.org/results/data-visualizations MALE 30% RISK OF DEATH* CARDIOVASCULAR 32% CANCER 36% FEMALE 20% RISK OF DEATH* CANCER 40% CARDIOVASCULAR 25% NEUROLOGIC 3% CIRRHOSIS 3% DIABETES 6% RESPIRATORY 7% OTHER 13% RESPIRATORY 10% DIABETES 10% CIRRHOSIS 5% NEUROLOGIC 5%OTHER 5%
  • 14. CONFIDENTIAL NOT FOR DISTRIBUTION 14 Approaches to Curative and Preventive Medicine Curative Preventive Identify pathology Identify risk Restore health Decrease risk Promote individual service ethic Responsibility is to the population Clinical intervention predominates Behavioral and social interventions are prominent, accompanied by clinical interventions Fineberg H. JAMA 2013; 310(1):85-90
  • 15. CONFIDENTIAL NOT FOR DISTRIBUTION 15 Health Nucleus: PROACTIVE Curative AND Preventive Medicine PROACTIVE Curative AND Preventive Identify pathology and risk Restore health and decrease risk Promote individual (and family/community) service ethic Clinical, behavioral, and social interventions
  • 16. CONFIDENTIAL NOT FOR DISTRIBUTION 16 Multi-Modality Data Gathering Genomics Sciences, Historical Context, Quantitative Testing  Whole-genome (30x)  Microbiome  Metabolomics  Family & Med Hx  Social  Environmental  Nutrition/Exercise  Advanced Imaging (full body MRI, Coronary CT)  Multi-Functional Testing  Exhaustive Labs
  • 17. CONFIDENTIAL NOT FOR DISTRIBUTION 17 HEALTH NUCLE I CASE STUDY 150GB OVER AN 8 HOUR DAY Collected Heath Data (6-8 hr visit) 1. WHOLE BODY • MRI (Musculoskeletal/ Lipid Analysis) • MRI (Organ Specific RSI) • DEXA Scan • In Body Biometrics • Over 70 Laboratory Diagnostic Tests • 3D Forensic Imaging 2. SEQUENCING • Whole Genome • Metabolome • Microbiome 3. BRAIN • NeuroQuant® Brain MRI • 3D T2 Brain MRI • Diffusion MRI • Neurocognitive Testing • Quant. Gait Analysis 4. PULMONOLOGY • Pulmonary Function • Testing 5. CARDIO-Vascular • Echo (2D, 3D, 4D) • ECG • CT Scan (Coronary Calcium Scoring) • 2 Week Ambulatory Rhythm Testing 2 1 3 4 5
  • 18. CONFIDENTIAL NOT FOR DISTRIBUTION 18 HEALTH NUCLE I CASE STUDY Fully-Automated, PACS-Integrated, Volumetric MRI Alzheimer’sNormal HEALTH NUCLE I CASE STUDY
  • 19. CONFIDENTIAL NOT FOR DISTRIBUTION 19 Magnetic Resonance-Based Restricted Spectrum Imaging for Early Cancer Detection Cellularity Index Nathan S. White et al. Cancer Res 2014;74:4638-4652 restricted Time1/2 Displacement RSI Model Time 10 ms 20 ms 60 ms
  • 20. CONFIDENTIAL NOT FOR DISTRIBUTION 20 HEALTH NUCLE I CASE STUDY A DYNAMIC EXPERIENCE THAT ALLOWS YOU TO EXPLORE YOUR HEALTH • Review your report with you and your physician • Develop a personalized healthcare strategy • Personal avatar and healthcare record The Living Avatar Report
  • 21. CONFIDENTIAL NOT FOR DISTRIBUTION 21 Genomic & Phenotype Findings to Identify Disease & Predict Risk (n=209) Cardiovascular Genomic Risk Mendelian GWAS* 20 (10%) 79 (38%) Cancer Phenotype Findings 151 (72%) 78 (37%)3 (1%) 5 (2%) Metabolic Neurodegenerative 27 (13%) 24 (11%) 91 (44%) 11 (5%) 26 (12%) 4 (2%) *Genome-Wide Association Study Other 64 (31%) 95 (46%) 6 (3%)
  • 22. CONFIDENTIAL NOT FOR DISTRIBUTION 22 Medicine has been a clinical science, supported by data. Medicine is about to become a data science, supported by clinicians.
  • 23. CONFIDENTIAL NOT FOR DISTRIBUTION 2323 PRESENTED TO CONFIDENTIAL NOT FOR DISTRIBUTION

Editor's Notes

  1. Reduced Sequencing Costs: Cost of full human genome sequencing dropped from $100M (2004) to ~$1000 (2014)1 Computational Power: Per Moore’s law, on average, price per unit of computing is halved every 24 months2 Machine Learning: Machine learning becomes mainstream due to quality breakthroughs and the exponential increase in data availability Cellular Therapies: ~5% of newborns have their cord blood stem cells banked each year – with 5 new cell therapies approved in the same timeframe.4 HLI will enable people to live longer, healthier lives by creating the World’s best knowledge solution to help life sciences companies quickly unlock the power of integrated genomics data to accelerate the path to cure, physicians to practice every day precision medicine, and consumers to be empowered to make sense of their biology and identify new cures in real time. 1. http://www.forbes.com/sites/matthewherper/2014/01/14/the-1000-genome-arrives-for-real-this-time/ 2. Mooreslaw.org 3. TBD 4. A Jain PharmaBiotech Report, Sept 2014 ( Cell Therapy Part II: Markets, Companies & Academic Institutions; Page Table 10:6) It is esimated that by the end of 2014, over 228,000 full human genomes will be sequenced.4 4. Global Genomse Sequenced: source: http://www.technologyreview.com/news/531091/emtech-illumina-says-228000-human-genomes-will-be-sequenced-this-year/
  2. Notice the limitations
  3. Restriction Spectrum Imaging is an advanced diffusion MRI technique for probing tissue microstructure in vivo. At short diffusion times (< 10 ms), diffusion MRI signals are dominated by the intrinsic diffusion constants of intracellular / extracellular compartments. At long diffusion times relevant to typical clinical MRI systems (50-100 ms) water molecules probe much larger length scales and displacements reflect local geometry and characteristics of tissue compartments. RSI is a novel model-based diffusion method to separate diffusion compartments with different size scales and geometries. Shown here is the separation of hindered extracellular water from restricted water trapped within spherical cell bodies. The volume fraction of the spherically restricted water is used as a quantitative surrogate measure of tumor cellularity. The methods are described in http://www.ncbi.nlm.nih.gov/pubmed/23169482 http://www.ncbi.nlm.nih.gov/pubmed/25183788