Transcript PPT - Larry Smarr - California Institute for Telecommunications and

“The Digital Transformation
of Healthcare”
Guest Lecture
Pharmacy Informatics 2014
University of California San Diego
June 2, 2014
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
1
http://lsmarr.calit2.net
The Vision of Digitally Enabled Genomic Medicine
is an Emerging Reality
2
July/August 2011
February 2012
The Emergence of P4 Medicine -Predictive, Preventive, Personalized, Participatory
Systems Biology &
Systems Medicine
Consumer-Driven
Social Networks
P4
MEDICINE
Digital Revolution
Big Data
Converging Megatrends
Driving the Transformation of Healthcare for Patients
Source: Lee Hood, ISB
100 Pioneer Wellness Project:
Started March 2014 –I Am One of The 100
Source:
Lee Hood, ISB
By
How
Measuring
Did I Get the
Started?
State IofArrived
My Body
in La
and
Jolla
“Tuning”
in 2000It
and
Using
Decided
Nutrition
to Move
and Exercise,
Against the
I Became
ObesityHealthier
Epidemic
Age
41
Age
51
Age
61
1999
2000
1999
1989
I Reversed My Body’s Decline By
Quantifying and Altering Nutrition and Exercise
http://lsmarr.calit2.net/repository/LS_reading_recommendations_FiRe_2011.pdf
2010
Wireless Monitoring
Helps Drive Exercise Goals
Quantifying My Sleep Pattern Using a Zeo Increased My Average to 8 Hours/Night
Stroke risk increased by sleeping less than six hours a night
-M. Ruiter, Sleep 2012
REM is Normally 20% of Sleep
Mine is Between 45-65% of Sleep
An Infant Typically
Has 50% REM
From Measuring Macro-Variables
to Measuring Your Internal Variables
www.technologyreview.com/biomedicine/39636
Visualizing Time Series of
150 LS Blood and Stool Variables, Each Over 5-10 Years
Calit2 64 megapixel VROOM
Only One of My Blood Measurements
Was Far Out of Range--Indicating Chronic Inflammation
27x Upper Limit
Episodic Peaks in Inflammation
Followed by Spontaneous Drops
Normal Range
<1 mg/L
Normal
Complex Reactive Protein (CRP) is a Blood Biomarker
for Detecting Presence of Inflammation
But by Using Stool Analysis Time Series, I Discovered
I Had Oscillating Immune Variables Far Above Normal
Typical
Lactoferrin
Value for
Active
IBD
124x Upper Limit
Normal Range
<7.3 µg/mL
Lactoferrin is a Protein Shed from Neutrophils An Immune System Antibacterial that Sequesters Iron
Colonoscopy Images Show
Inflamed Pseudopolyps in 6 inches of Sigmoid Colon
Dec 2010
Jan 2012
Confirming the IBD (Crohn’s) Hypothesis:
Finding the “Smoking Gun” with MRI Imaging
Liver
Transverse Colon
Small Intestine
I Obtained the MRI Slices
From UCSD Medical Services
and Converted to Interactive 3D
Working With
Calit2 Staff & DeskVOX Software
Descending Colon
MRI Jan 2012
Cross Section
Diseased Sigmoid Colon
Major Kink
Sigmoid Colon
Threading Iliac Arteries
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
So I Set Out to Quantify All Three!
Paul B. Eckburg & David A. Relman
Clin Infect Dis. 44:256-262 (2007)
The Cost of Sequencing a Megabase of DNA
Has Fallen Over 10,000x in the Last Ten Years!
This Has Enabled Sequencing of
Both Human and Microbial Genomes
I Wondered if Crohn’s is an Autoimmune Disease,
Did I Have a Personal Genomic Polymorphism?
From www.23andme.com
ATG16L1
Polymorphism in
Interleukin-23 Receptor Gene
— 80% Higher Risk
of Pro-inflammatory
Immune Response
IRGM
NOD2
SNPs Associated with CD
I am Now an Advisor
on the
23andme IBD Project
Imagine Crowdsourcing 23andme SNPs
For Even a Small Portion of Crohnology!
www.crohnology.com
Crowd-Sourcing the Effectiveness
of Pharmaceutical Medications for Crohn’s Disease
www.crohnology.com
Treating the Human Superorganism:
Your Body Has Ten Microbes for Every Human Cell!
Nature Reviews
Microbiology
v.9, p. 279 (2011)
To Map Out the Dynamics of My Microbiome Ecology
I Partnered with the J. Craig Venter Institute
• JCVI Did Metagenomic
Sequencing on Seven of
My Stool Samples
Over 1.5 Years
• Sequencing on
Illumina HiSeq 2000
– Generated 200 Million
100bp Reads
Illumina HiSeq 2000 at JCVI
• JCVI Lab Manager,
Genomic Medicine
– Manolito Torralba
• IRB PI Karen Nelson
– President JCVI
Manolito Torralba, JCVI
Karen Nelson, JCVI
We Downloaded Additional Gut Microbiomes
from NIH HMP For Comparative Analysis
From Sequences to Bacterial Species Relative Abundance
Required 25 CPU-Years at San Diego Supercomputer Center
“Healthy” Individuals
IBD Patients
250 Subjects
1 Point in Time
Larry Smarr
2 Ulcerative Colitis Patients,
6 Points in Time
6 Points in Time
5 Ileal Crohn’s Patients,
3 Points in Time
Total of 27 Billion Reads
Or 2.7 Trillion Bases
Source: Jerry Sheehan, Calit2
Weizhong Li, Sitao Wu, CRBS, UCSD
We Found Major Shifts in Microbial Ecology
Between Healthy and Two Forms of IBD
Explosion of
Proteobacteria
On the IBD Spectrum
Collapse of
Bacteroidetes
Tracking How 1 Month Antibiotic, 2 Months Prednisone Therapy
Alters the Gut Microbial Ecology
Reduced 45x
Reduced 90x
Therapy Greatly Reduced Two Phyla,
But Massive Reduction in Bacteroidetes
And Large % Proteobacteria Remain
Small Changes
With No Therapy
How Does One Get Back
to a “Healthy” Gut Microbiome?
Comparing Changes in Gut Microbiome Ecology with
Oscillations of the Innate and Adaptive Immune System
LS Data from Yourfuturehealth.com Stool Tests
Innate Immune System
Normal
Therapy: 1 Month Antibiotics
+2 Month Prednisone
Adaptive Immune System
Normal
Time Points of
Metagenomic
Sequencing
of LS Stool Samples
Time Series Reveals Autoimmune Dynamics
of Gut Microbiome by Phyla
Therapy
Six Metagenomic Time Samples Over 16 Months
Toward Microbiome Disease Diagnosis
UC 100x Healthy
CD 100x Healthy
Inexpensive 16S Time Series of Microbiome
Now Possible Through Ubiome
Data source: LS (Yellow Lines Stool Samples);
Sequencing and Analysis Ubiome
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.”
Evidence for the Efficacy of Probiotics is IBD is Mixed More Clinical Research Needed
“...there is virtually no evidence of probiotic efficacy in Crohn’s disease.”
From the Single “Bad” Microbe Medical Target
to the Microbiome Ecology Paradigm
Sci Transl Med 4, 137rv5 (2012);
Science 336, 1255 (2012)
Problem of Alternative Stable States
In Ecological System Dynamics
Microbiome Transfer
May Be a Radical New Treatment for IBD
Procedures
Starting With
Natural Microbiome
Dr. Alexander Khoruts, NY Times
www.nytimes.com/2010/07/13/science/13micro.html
Next Steps:
Create
Synthetic Microbiomes
Tuned to the Patient
See
Microbiome 1:3 (2013)
Not FDA Approved Yet;
Increasing Number of Doctors Performing Procedure;
Clinical Trials Under Way;
Encouraging Results…
www.gihealthfoundation.org/reuters/articles.cfm?article=20111102drgd011
Next Decade Will See New Microbiome
“Gardening Tools”
August 7, 2012
Journal of Nanotechnology (2012)
The Disruption of Consumer Health Data Gathering
Is Growing Rapidly
Blood Variable Time Series
Stool Variable Time Series
Human Genetic Variations
MicrobiomeTime Series
Thanks to Our Great Team!
UCSD Metagenomics Team
JCVI Team
Weizhong Li
Sitao Wu
Karen Nelson
Shibu Yooseph
Manolito Torralba
SDSC Team
Calit2@UCSD
Future Patient Team
Jerry Sheehan
Tom DeFanti
Kevin Patrick
Jurgen Schulze
Andrew Prudhomme
Philip Weber
Fred Raab
Joe Keefe
Ernesto Ramirez
Michael Norman
Mahidhar Tatineni
Robert Sinkovits
UCSD Health Sciences Team
William J. Sandborn
Elisabeth Evans
John Chang
Brigid Boland
David Brenner