“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
http://lsmarr.calit2.net 1
The Vision of Digitally Enabled Genomic Medicineis an Emerging Reality
2
July/August 2011 February 2012
The Emergence of P4 Medicine --Predictive, Preventive, Personalized, Participatory
Converging Megatrends Driving the Transformation of Healthcare for Patients
Systems Biology & Systems Medicine
Consumer-Driven Social Networks
P4 MEDICINE
Digital RevolutionBig Data
Source: Lee Hood, ISB
100 Pioneer Wellness Project: Started March 2014 –I Am One of The 100
Source: Lee Hood, ISB
By Measuring the State of My Body and “Tuning” ItUsing Nutrition and Exercise, I Became Healthier
2000
Age 41
2010
Age 61
1999
1989
Age 51
1999
How Did I Get Started? I Arrived in La Jolla in 2000and Decided to Move Against the Obesity Epidemic
I Reversed My Body’s Decline By Quantifying and Altering Nutrition and Exercise
http://lsmarr.calit2.net/repository/LS_reading_recommendations_FiRe_2011.pdf
Wireless Monitoring Helps Drive Exercise Goals
Quantifying My Sleep Pattern Using a Zeo -Increased My Average to 8 Hours/Night
REM is Normally 20% of SleepMine is Between 45-65% of Sleep
An Infant Typically Has 50% REM
Stroke risk increased by sleeping less than six hours a night-M. Ruiter, Sleep 2012
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
Normal Range<1 mg/L
Normal
27x Upper Limit
Episodic Peaks in Inflammation Followed by Spontaneous Drops
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
Normal Range<7.3 µg/mL
124x Upper Limit
Lactoferrin is a Protein Shed from Neutrophils -An Immune System Antibacterial that Sequesters Iron
TypicalLactoferrin Value for
Active IBD
Colonoscopy Images Show Inflamed Pseudopolyps in 6 inches of Sigmoid Colon
Dec 2010 Jan 2012
Descending Colon
Sigmoid ColonThreading Iliac Arteries
Major Kink
Confirming the IBD (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 ColonLiver
Small Intestine
Diseased Sigmoid ColonCross Section
MRI Jan 2012
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. RelmanClin Infect Dis. 44:256-262 (2007)
So I Set Out to Quantify All Three!
The Cost of Sequencing a Megabase of DNAHas 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
SNPs Associated with CD
Polymorphism in Interleukin-23 Receptor Gene
— 80% Higher Risk of Pro-inflammatoryImmune Response
NOD2
ATG16L1
IRGM
I am Now an Advisoron the
23andme IBD Project
Imagine Crowdsourcing 23andme SNPsFor Even a Small Portion of Crohnology!
www.crohnology.com
Crowd-Sourcing the Effectivenessof 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
• JCVI Lab Manager, Genomic Medicine– Manolito Torralba
• IRB PI Karen Nelson– President JCVI
Illumina HiSeq 2000 at JCVI
Manolito Torralba, JCVI Karen Nelson, JCVI
We Downloaded Additional Gut Microbiomesfrom NIH HMP For Comparative Analysis
5 Ileal Crohn’s Patients, 3 Points in Time
2 Ulcerative Colitis Patients, 6 Points in Time
“Healthy” Individuals
From Sequences to Bacterial Species Relative AbundanceRequired 25 CPU-Years at San Diego Supercomputer Center
Source: Jerry Sheehan, Calit2Weizhong Li, Sitao Wu, CRBS, UCSD
Total of 27 Billion ReadsOr 2.7 Trillion Bases
IBD Patients
250 Subjects1 Point in Time
Larry Smarr6 Points in Time
We Found Major Shifts in Microbial EcologyBetween Healthy and Two Forms of IBD
Collapse of Bacteroidetes
Explosion of Proteobacteria On the IBD Spectrum
Tracking How 1 Month Antibiotic, 2 Months Prednisone TherapyAlters 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
Normal
Innate Immune System
Normal
Adaptive Immune System
Time Points of Metagenomic Sequencing
of LS Stool Samples
Therapy: 1 Month Antibiotics+2 Month Prednisone
LS Data from Yourfuturehealth.com Stool Tests
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 MicrobiomeNow 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 Targetto the Microbiome Ecology Paradigm
Sci Transl Med 4, 137rv5 (2012);
Science 336, 1255 (2012)
Problem of Alternative Stable StatesIn Ecological System Dynamics
Microbiome TransferMay Be a Radical New Treatment for IBD
www.gihealthfoundation.org/reuters/articles.cfm?article=20111102drgd011
Dr. Alexander Khoruts, NY Timeswww.nytimes.com/2010/07/13/science/13micro.html
Not FDA Approved Yet;Increasing Number of Doctors Performing Procedure;
Clinical Trials Under Way;Encouraging Results…
ProceduresStarting With
Natural Microbiome
Next Steps:Create
Synthetic MicrobiomesTuned to the Patient
SeeMicrobiome 1:3 (2013)
Next Decade Will See New Microbiome“Gardening Tools”
Journal of Nanotechnology (2012)
August 7, 2012
The Disruption of Consumer Health Data GatheringIs Growing Rapidly
Blood Variable Time Series Stool Variable Time Series
MicrobiomeTime SeriesHuman Genetic Variations
Thanks to Our Great Team!
UCSD Metagenomics Team
Weizhong LiSitao Wu
Calit2@UCSD Future Patient Team
Jerry SheehanTom DeFantiKevin PatrickJurgen SchulzeAndrew PrudhommePhilip WeberFred RaabJoe KeefeErnesto Ramirez
JCVI Team
Karen NelsonShibu YoosephManolito Torralba
SDSC Team
Michael NormanMahidhar Tatineni Robert Sinkovits
UCSD Health Sciences Team
William J. SandbornElisabeth EvansJohn ChangBrigid BolandDavid Brenner