Wearables and PrecisonHealth

Michael Snyder

March 13th, 2019

Conflicts: Personalis, Genapsys, SensOmics, Qbio, January, Filtricine, Akna

• Focused on Health• Proactive• Measure many things• Frequent?• Individual based

• Focus on Illness• Reactive• Measure very few things• Infrequent• Population based

MedicinePresently Should be

Precision Health

Health

Genome

Food

Health Is a Product of Genome, Exposome, Lifestyle

Environmental Exposures

ExerciseLifestyle

Stress

Genome

Transcriptome

Proteome

MetabolomeLipidomics

Autoantibody-ome

Longitudinal Personal Omics Profiling

Cytokines

Epigenome

Billions of Measurements!

Microbiome (Gut, Urine, Nasal, Tongue, Skin)

OmicsMeasurements

4

Year 2 …Year 1 Viral infection

Biosensors

Clinical TestsQuestionaires

Stress EchosGlucose Control

107 Individuals 5.5 yrs

Metabolic

Infectious

Other Heme/Onc

Cardiovascular

7 Oncologic Risk Genes(Thyroid Cancer in 1)

1 Lymphoma (Imaging)1 MGUS (IgM) 1 Smoldering Myeloma (IgM)1 α Thalassemia (Clinical) 1 β Thalassemia (Gene/Clinical)1 Pros1 Mutation (gene)

1 Lyme Disease (wearable)

6 Carotid Plaques (imaging)1 Atrial Fib. (wearable)1 RMB20 mutation (gene)1 Reduced LVEF/GLS (imaging)3 Dilated L. Atrium (imaging) 1 Pharmagenomic (gene)

1 Sleep Apnea (wearable)1 SLC7A9 mutation (cystinuria risk)2 Macroalbuminuria

1 MODY mutation (gene)1 ABCC8 Mutation (gene)14 New Diabetes

49 Major Health Discoveries

Rose, Contrepois et al. Nat. Medicine, in press

Discovery of B-Cell Lymphoma

Rose, Contrepois et al. Nat. Medicine, in press

Transitions in DM status

Rose, Contrepois et al. Nat. Medicine, in press

−20

0

20

40

−60 −40 −20 0 20 40MDS1

MDS2

−5.0

−2.5

0.0

2.5

5.0

−8 −4 0 4MDS1

MDS2

Cytokines

ClinicLabs

−1000

0

1000

−1000 0 1000MDS1

MDS2

−4000

0

4000

8000

−20000 −10000 0 10000MDS1

MDS2

Metabolome

Transcriptome

Strong Personal CharacteristicsMultiDimensional Scaling for 12 subjects with at least 10 healthy baseline visits

Basis B1Basis

Peak

Apple Watch

Dexcom Constant Glucose Monitor

Withthings Smart Scale

Qardio Blood Pressure Cuff

ScanaduScout

Autographer – Life Logger

iHealth Pulse Oximeter

Athos – Smart Shorts

RadtargeRadiation

Sensors: Over 900 Devices

Li, Dunn et al. PloS Biol 2017

Δ Sk

in T

emp

(Nig

ht –

Day

)Δ

HR

(Nig

ht –

Day

)

43 People: All are different

SpO2 Levels Drop During Airline Flights

SpO2Measurements

Associated With Fatigue

Li, Dunn et al. PloS Biol 2017

Early detection of Lyme disease

% o

f out

lier (

HR

)%

of o

utlie

r (Sk

in te

mp.

)

Day 458 470 474462 466 478 482 486 490 494

Detects All Days of Illness

Li, Dunn et al. PloS Biol 2017

Change-of-Heart Algorithm

Continuous Glucose Monitoring: Lots of Spikers

24 hours

2-4 weeks

Dexcom G415

Classification of People into Glucotypes Based on CGM Profiles

Segment CGM profiles into windows and cluster

Glucotypes

The same meal triggers different glycemic responses in different people

Bread + Peanut Butter

Protein Bar

Cornflakes + Milk

Glucotype classification may help find diabetes risk

18Clustering based n clinical and glucose data

Latest Wearable: Human Exposome

Biotics Abiotics

Asthma & allergies strike

1 out of 5Americans

Carcinogens,Pollutants,Smoke

Identify Personal Exposomes:Track individuals up to 890 days

Flow rate: 0.5L/min

Average human breathes in 11L/min

CartridgesFilters

P1 n=201P2 n=33P3 n=12P4 n=4P5 n=4P6 n=2P7 n=3P8 n=7

Others n=17

Total N=283

2014−072014−1

02015−0

12015−0

42015−0

72015−1

02016−0

12016−0

42016−0

72016−1

02017−0

1

Date

Ind

ivid

ua

l

Season spring summer fall winter

Timelines

−50

−25

0

25

50

−100 0 100Longitude

Latitude

37.3

37.5

37.7

37.9

−122.4 −122.2 −122.0 −121.8Longitude

Latitude

P1P2P3

What can we capture?(Minus human reads)

>2500 species~300/sample

>70 billion reads>10 Trillion base pairs> 7 million assembled contigs

Empty filter Pine Pollen

Brochosomes“Stem rust” spores Inorganic materials

(water repellent coating on

insects)

Puccinia graminis

Eucalyptus Pollen

Dynamic exposome specific to individuals

Timeline

P1

P2

P3

Kingdom level

890 days

429 days

301 days

P1 P2 P3Plant

FungiBacteria Mixed

Season and location matterP1 Samples: Location

P1 Samples: Season

Forward-selected variables from a collection of 64 meta-variables

Location, location, locationDifferent persons, same month

San FranciscoAlkanindiges: Sludge bacteriaKlebsiella: pneumonia pathogen

Seasonal influence on the genera

Pine tree sheds millions of pollens

“False Turkey Tail”, spore season starts around fall

season spring summer fall winter

*

***

*Kruskal−Wallis, p = 0.00016

0

5

10

15

Ster

eum

hirs

utum

0

5

10

3 4 5 6 7 8 9 10 11 12 1 2

Chemicals are influenced by locationLocation Bethesda−MD

Boston−MACampusDavis−CA

East_Lansing−MIHouston−TX

MontanaSF−CA

−2

0

2

Phth

alat

e

−2

0

2

Geo

smin

−2

0

2

Capr

ylic

acid

−2

0

2

SF−CA

Campu

s

Campu

s

Campu

s

Montan

a

Housto

n−TX

Campu

s

Campu

s

Campu

s

Boston−M

A

Campu

s

East_L

ansin

g−MI

Davis−

CA

Boston−M

A

Bethes

da−M

D

Om

etho

ate

“Earthy” smell

Pesticide

Plastic components

Body Scent

Chemicals are correlated with biologicalsLocation Bethesda−MDBoston−MA

CampusDavis−CA

East_Lansing−MIHouston−TX

MontanaSF−CA

−2

0

2

Phlebiopsis

−2

0

2

Gym

nopus

−2

0

2

Lentinus

−2

0

2Coniosporium

−202

SF−CA

Campus

Campus

Campus

Montana

Houston−TX

Campus

Campus

Campus

Boston−MA

Campus

East_Lansing−MI

Davis−CA

Boston−MA

Bethesda−MD

PyridineOrganic

solvent, used in paint

Common Fungal genera

The Exposome Cloud – connections between detected species

Smart Phone = Control Center

Acknowledgements

31

Snyder LabWenyu ZhouBrian PieningKevin ContrepoisTejaswini MishraKim KukurbaShannon RegoJessica SibalHannes RostVarsha RaoLiang LiangTejas MishraChristine YehHassan ChaibEric WeiMonica Avina

WearablesXiao LiJessie DunnDenis SalinsSophia Miryam …Heather Hall

Weinstock LabGeorge WeinstockErica SodergrenYanjiao ZhouShana LeopoldDaniel SpakowiczBlake HansonEddy BautistaLauren PetersenLei ChenBenjamin LeopoldSai LekPurva Vats

Jon Bernstein

NIHLita ProctorSalvatore SechiJon LoTempioAnd other

McLaughlin LabTracy McLaughlinColleen CraigCandice AllisterDalia PerelmanElizabeth Colbert

ExposomeChao JiangXin WangJingga InloraTing WangXiyan Li

32

The Future?Genomic Sequencing

1. Predict risk2. Early Diagnose3. Monitor4. Treat

GGTTCCAAAAGTTTATTGGATGCCGTTTCAGTACATTTATCGTTTGCTTTGGATGCCCTAATTAAAAGTGACCCTTTCAAACTGAAATTCATGATACACCAATGGATATCCTTAGTCGATAAAATTTGCGAGTACTTTCAAAGCCAAATGAAATTATCTATGGTAGACAAAACATTGACCAATTTCATATCGATCCTCCTGAATTTATTGGCGTTAGACACAGTTGGTATATTTA….

Amanda Mills

Omes & Sensors: Personal Devices

SpO2Measurements

Can Adapt on Flights >7hrs

Share Information With Physician

Importance in Individual Variation from “Normal”

Sund-Levander M. Scand J Caring Sci 2002;122-8. & Souissi N. Chronobio Int 2007;24:739 -48

Oral temp in 2749 healthy individuals

100.8F

99.1F

97.5F

94.6F

92.0F

Sequences related to pathogens: rare

Species level

6 people with Carotid Plaque

MGUS PreCancer: High IgM

Rose, Contrepois et al. Nat. Medicine, in press

Circadian and diurnal patterns

Li, Dunn et al. PloS Biol 2017