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Quantifying the Self: An N=1 Case Study
1. “The Deeply Quantified Self:
A Case Study”
Future Technology Keynote
Minimally Invasive Surgery Week 2015
Society of Laparoendoscopic Surgeons
New York City, NY
September 5, 2015
Dr. Larry Smarr
Director, California Institute for Telecommunications and Information Technology
Harry E. Gruber Professor,
Dept. of Computer Science and Engineering
Jacobs School of Engineering, UCSD
http://lsmarr.calit2.net
1
2. By Measuring the State of My Body and “Tuning” It
Using Nutrition and Exercise, I Became Healthier
2000
Age
41
2010
Age
61
1999
1989
Age
51
1999
I Arrived in La Jolla in 2000 After 20 Years in the Midwest
and Decided to Move Against the Obesity Trend
I Reversed My Body’s Decline By
Quantifying and Altering Nutrition and Exercise
http://lsmarr.calit2.net/repository/LS_reading_recommendations_FiRe_2011.pdf
3. Calit2 Has Been Had a Vision of
“the Digital Transformation of Health” for 15 Years
• Next Step—Putting You On-Line!
– Wireless Internet Transmission
– Key Metabolic and Physical Variables
– Model -- Dozens of Processors and 60 Sensors /
Actuators Inside of our Cars
• Post-Genomic Individualized Medicine
– Combine
–Genetic Code
–Body Data Flow
– Use Powerful AI Data Mining Techniques
www.bodymedia.com
The Content of This Slide from 2001 Larry Smarr
Calit2 Talk on Digitally Enabled Genomic Medicine
4. I Used a Variety of Emerging Personal Sensors
To Quantify My Body & Drive Behavioral Change
Withings/iPhone-
Blood Pressure
Zeo-Sleep
Azumio-Heart Rate
MyFitnessPal-
Calories Ingested
FitBit -
Daily Steps &
Calories Burned
Withings WiFi Scale -
Daily Weight
5. Wireless Monitoring
Produced Time Series That Helped Me Improve My Health
Since Starting November 3, 2011
Total Distance Tracked 3,223 miles = San Diego to Bangor, ME
Total Vertical Distance Climbed 107,000 ft. = 3.7 Mt. Everest
Using Polar Chest Strap
During Elliptical WorkoutsMy Resting Heartrate
Fell from 70 to 40!
6. Quantifying My Sleep Pattern Using Zeo -
Surprisingly About Half My Sleep is REM!
REM is Normally 20% of Sleep
Mine is Between 45-65% of Sleep
An Infant Typically
Has 50% REM
8. Quantifying Your Inner Self:
A Case Study
An N=1 Case Study of Using Quantified Self
To Discover and Track an Autoimmune Disease
9. I Have Turned My Body into
a Genomic and Biomarker Observatory
One Blood Draw
For MeCalit2 64 Megapixel VROOM
10. Only One of My Blood Measurements
Was Far Out of Range--Indicating Chronic Inflammation
Normal Range <1 mg/L
27x Upper Limit
Complex Reactive Protein (CRP) is a Blood Biomarker
for Detecting Presence of Inflammation
Episodic Peaks in Inflammation
Followed by Spontaneous Drops
11. Adding Stool Tests Revealed
Oscillatory Behavior in an Immune Variable Which is Antibacterial
Normal Range
<7.3 µg/mL
124x Upper Limit for Healthy
Lactoferrin is a Protein Shed from Neutrophils -
An Antibacterial that Sequesters Iron
Typical
Lactoferrin Value for
Active Inflammatory
Bowel Disease
(IBD)
12. Colonoscopy Images Show Persistent
Inflamed Pseudopolyps in 6 inches of Sigmoid Colon
Dec 2010 Jan 2012
“Inflammatory polyp versus inflamed fold in the distal sigmoid colon
and apthous ulcers in the rectum, consistent with active Crohn’s colitis.”
William J. Sandborn, MD UCSD Jan 3, 2012
13. Descending Colon
Sigmoid Colon
Threading Iliac Arteries
Major Kink
Confirming the Colonic Crohn’s Hypothesis:
Finding the “Smoking Gun” with MRI Imaging
I Obtained the MRI Slices
From UCSD Medical Services
and Converted to Interactive 3D
Working With
Calit2 Staff & DeskVOX Software
Transverse Colon
Liver
Small Intestine
Diseased Sigmoid Colon
Cross Section
MRI Jan 2012
14. MRE Reveals Inflammation in 6 Inches of Sigmoid Colon
Thickness 15cm – 5x Normal Thickness
“Long segment wall thickening
in the proximal and mid portions of the sigmoid colon,
extending over a segment of approximately 16 cm,
with suggestion of intramural sinus tracts.
Edema in the sigmoid mesentery
and engorgement of the regional vasa recta.”
– Cynthia Santillan, MD Radiologist
MRI report
Jan 2012
Clinical MRI
Slice Program
DeskVOX 3D Image
3D vs. 2D Visualization
Of DICOM file of LS MRI
Wall Thickness 5x Normal
15. Why Did I Have an Autoimmune Disease like IBD?
Despite decades of research,
the etiology of Crohn's disease
remains unknown.
Its pathogenesis may involve
a complex interplay between
host genetics,
immune dysfunction,
and microbial or environmental factors.
--The Role of Microbes in Crohn's Disease
Paul B. Eckburg & David A. Relman
Clin Infect Dis. 44:256-262 (2007)
I Have Been Quantifying All Three
16. The Cost of Sequencing a Human Genome
Has Fallen Nearly 10,000x in the Last Ten Years
This Has Enabled Sequencing of
Both Human and Microbial Genomes
17. Person A
Person B
Single Nucleotide Polymorphisms (SNPs) Make Up
About 90% of All Human Genetic Variation
www.23andme.com Tracks One Million SNPs
SNPs Occur Every
100 to 300 Bases
Along Human DNA
18. I Found I Had One of the Earliest Known SNPs
Associated with Crohn’s Disease
From www.23andme.com
SNPs Associated with CD
Interleukin-23 Receptor Gene
— 80% Higher Risk
of Pro-inflammatory
Immune Response
NOD2
IRGM
ATG16L1
23andme
is Seeking 10,000 Volunteers
with IBD
to Determine SNP Distribution
to Stratify Disease Spectrum
19. To Understand the Interaction of Genetics with Disease States
We Must Consider the Human Microbiome and Not Just the Human Genome
Your Microbiome is
Your “Near-Body” Environment
and its Cells
Contain 300x
as Many DNA Genes
As Your Human Cells
Your Body Has 10 Times
As Many Microbe Cells As Human Cells
20. June 8, 2012 June 14, 2012
Interest in the Human Microbiome
Has Moved Quickly From Frontier Science to Public Awareness
August 18, 2012June, 2012
21. When We Think About Biological Diversity
We Typically Think of the Wide Range of Animals
But All These Animals Are in One SubPhylum Vertebrata
of the Chordata Phylum
All images from Wikimedia Commons.
Photos are public domain or by Trisha Shears & Richard Bartz
22. Think of These Phyla of Animals When
You Consider the Biodiversity of Microbes Inside You
All images from WikiMedia Commons.
Photos are public domain or by Dan Hershman, Michael Linnenbach, Manuae, B_cool
Phylum
Annelida
Phylum
Echinodermata
Phylum
Cnidaria
Phylum
Mollusca
Phylum
Arthropoda
Phylum
Chordata
23. The Genetic Distance Between Microbes
Vastly Exceeds That Among All Animals and Plants
You
Are
Here
Source: Carl Woese, et al
Tree of Life Derived from 16S rRNA Sequences
24. To Map Out the Dynamics of Autoimmune Microbiome Ecology
Couples Next Generation Genome Sequencers to Big Data Supercomputers
Illumina HiSeq 2000 at JCVI
SDSC Gordon Data Supercomputer
Example: Inflammatory Bowel Disease (IBD)
We used 25 CPU-years
to compute
comparative gut microbiomes
starting from
7 trillion DNA bases
of my samples,
255 healthy,
and 20 IBD controls
25. We Found Major State Shifts in Microbial Ecology Phyla
Between Healthy and Three Forms of IBD
Most
Common
Microbial
Phyla
Average HE
Average
Ulcerative Colitis
Average LS
Colonic Crohn’s Disease
Average
Ileal Crohn’s Disease
Collapse of Bacteroidetes
Explosion of Actinobacteria
Explosion of
Proteobacteria
Hybrid of UC and CD
High Level of Archaea
26. This Year We Will Extend My Stool Time Series
Collaborating with the UCSD Knight Lab
Larry’s 40 Stool Samples Over 3.5 Years
to Rob’s lab on April 30, 2015
27. We Must Move From Combating Single Microbe Diseases to
Developing the Human/Microbiome System Approach to Public Health
Bach (2002) N Engl J Med, Vol. 347, 911-920
2014
For Public Health It is Still About Microbes,
But from Single Species to Entire Ecologies
28. The United States Population’s Human Gut Microbiome
Has Diverged a Great Deal from Hunter-Gatherers
“The microbiome of uncontacted Amerindians,” J. C. Clemente, et al. Science Advances 1, e1500183 (2015).
[Amerindians in
Venezuela/Columbia]
[Africa]
Human
Microbiome
Project
Missing Microbes
29. The Coupled Neural, Immune, and Microbiome Systems
Provide a Model Explaining How Nutrition Can Alter Neurodevelopment
30. From War to Gardening:
New Therapeutical Tools for Managing the Microbiome
“I would like to lose the language of warfare,”
said Julie Segre, a senior investigator at
the National Human Genome Research Institute.
”It does a disservice to all the bacteria
that have co-evolved with us
and are maintaining the health of our bodies.”
31. Reports Are Being Published on
The Birth of the Human Microbiome Market
www.insightpharmareports.com/human-microbiome-report
October 2014
32. Fecal Microbiome Transfer
Is a Rapidly Growing New Treatment for IBD
Dr. Bill Sandborn,
Chief UCSD GI
Dr. Brigid Boland,
UCSD GI
33. Where I Believe We are Headed:
Predictive, Personalized, Preventive, & Participatory Medicine
www.newsweek.com/2009/06/26/a-doctor-s-vision-of-the-future-of-medicine.html
Will Grow to 1000, Then 10,000,
Then 100,000
34. Genetic Sequencing of the DNA of Humans and Their Microbes
Is a Huge Growth Area and the Future Foundation of Medicine
Source: @EricTopol
Twitter 9/27/2014
35. From One to a Billion Data Points Defining Me:
The Exponential Rise in Body Data in Just One Decade
Billion: My Full DNA,
MRI/CT Images
Million: My DNA SNPs,
Zeo, FitBit
Hundred: My Blood VariablesOne:
My WeightWeight
Blood
Variables
SNPs
Microbial Genome
Improving Body
Discovering Disease
36. Thanks to Our Great Team!
UCSD Metagenomics Team
Weizhong Li
Sitao Wu
Calit2@UCSD
Future Patient Team
Jerry Sheehan
Tom DeFanti
Kevin Patrick
Jurgen Schulze
Andrew Prudhomme
Philip Weber
Fred Raab
Joe Keefe
Ernesto Ramirez
Ayasdi
Devi Ramanan
Pek Lum
JCVI Team
Karen Nelson
Shibu Yooseph
Manolito Torralba
SDSC Team
Michael Norman
Mahidhar Tatineni
Robert Sinkovits
UCSD Health Sciences Team
Rob Knight
William J. Sandborn
Elisabeth Evans
John Chang
Brigid Boland
David Brenner
Dell/R Systems
Brian Kucic
John Thompson