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“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
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The Vision of Digitally Enabled Genomic Medicine is an Emerging Reality
July/August 2011 February 2012
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Systems Biology & Systems Medicine Consumer-Driven Social Networks
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
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100 Pioneer Wellness Project: Started March 2014 –I Am One of The 100
Source: Lee Hood, ISB
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How Did I Get Started? I Arrived in La Jolla in 2000 and Decided to Move Against the Obesity Epidemic By Measuring the State of My Body and “Tuning” It Using Nutrition and Exercise, I Became Healthier Age 41 Age 51 1999 2010 Age 61 1999 2000 1989 I Reversed My Body’s Decline By Quantifying and Altering Nutrition and Exercise
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Wireless Monitoring Helps Drive Exercise Goals
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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
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MyFitnessPal- Calories Ingested
I Used a Variety of Emerging Personal Sensors To Quantify My Body & Drive Behavioral Change Withings/iPhone- Blood Pressure MyFitnessPal- Calories Ingested FitBit - Daily Steps & Calories Burned Azumio-Heart Rate Zeo-Sleep Withings WiFi Scale - Daily Weight
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From Measuring Macro-Variables to Measuring Your Internal Variables
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Visualizing Time Series of 150 LS Blood and Stool Variables, Each Over 5-10 Years
Calit2 64 megapixel VROOM
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Episodic Peaks in Inflammation Followed by Spontaneous Drops
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
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But by Using Stool Analysis Time Series, I Discovered I Had Oscillating Immune Variables Far Above Normal 124x Upper Limit Typical Lactoferrin Value for Active IBD Normal Range <7.3 µg/mL Lactoferrin is a Protein Shed from Neutrophils - An Immune System Antibacterial that Sequesters Iron
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Colonoscopy Images Show Inflamed Pseudopolyps in 6 inches of Sigmoid Colon
Jan 2012 Dec 2010
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I Obtained the MRI Slices From UCSD Medical Services
Confirming the IBD (Crohn’s) Hypothesis: Finding the “Smoking Gun” with MRI Imaging Liver I Obtained the MRI Slices From UCSD Medical Services and Converted to Interactive 3D Working With Calit2 Staff & DeskVOX Software Transverse Colon Small Intestine Descending Colon Sigmoid Colon Threading Iliac Arteries Major Kink Diseased Sigmoid Colon MRI Jan 2012 Cross Section
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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: (2007)
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This Has Enabled Sequencing of Both Human and Microbial Genomes
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
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I Wondered if Crohn’s is an Autoimmune Disease, Did I Have a Personal Genomic Polymorphism?
From Polymorphism in Interleukin-23 Receptor Gene — 80% Higher Risk of Pro-inflammatory Immune Response ATG16L1 IRGM NOD2 SNPs Associated with CD I am Now an Advisor on the 23andme IBD Project
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Imagine Crowdsourcing 23andme SNPs For Even a Small Portion of Crohnology!
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Crowd-Sourcing the Effectiveness of Pharmaceutical Medications for Crohn’s Disease
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Treating the Human Superorganism: Your Body Has Ten Microbes for Every Human Cell!
Nature Reviews Microbiology v.9, p. 279 (2011)
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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
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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 2 Ulcerative Colitis Patients, 6 Points in Time Larry Smarr 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
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We Found Major Shifts in Microbial Ecology Between Healthy and Two Forms of IBD
On the IBD Spectrum Explosion of Proteobacteria Collapse of Bacteroidetes
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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?
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Time Points of Metagenomic Therapy: 1 Month Antibiotics
Comparing Changes in Gut Microbiome Ecology with Oscillations of the Innate and Adaptive Immune System LS Data from Yourfuturehealth.com Stool Tests Time Points of Metagenomic Sequencing of LS Stool Samples Innate Immune System Normal Therapy: 1 Month Antibiotics +2 Month Prednisone Adaptive Immune System Normal
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Time Series Reveals Autoimmune Dynamics of Gut Microbiome by Phyla
Therapy Six Metagenomic Time Samples Over 16 Months
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Toward Microbiome Disease Diagnosis
UC 100x Healthy CD 100x Healthy
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Inexpensive 16S Time Series of Microbiome Now Possible Through Ubiome
Data source: LS (Yellow Lines Stool Samples); Sequencing and Analysis Ubiome
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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.”
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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.”
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Problem of Alternative Stable States In Ecological System Dynamics
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
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Microbiome Transfer May Be a Radical New Treatment for IBD
Procedures Starting With Natural Microbiome Next Steps: Create Synthetic Microbiomes Tuned to the Patient See Microbiome 1:3 (2013) Dr. Alexander Khoruts, NY Times Not FDA Approved Yet; Increasing Number of Doctors Performing Procedure; Clinical Trials Under Way; Encouraging Results…
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Next Decade Will See New Microbiome “Gardening Tools”
August 7, 2012 Journal of Nanotechnology (2012)
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The Disruption of Consumer Health Data Gathering Is Growing Rapidly
Blood Variable Time Series Stool Variable Time Series Human Genetic Variations MicrobiomeTime Series
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Thanks to Our Great Team!
UCSD Metagenomics Team Weizhong Li Sitao Wu Future Patient Team Jerry Sheehan Tom DeFanti Kevin Patrick Jurgen Schulze Andrew Prudhomme Philip Weber Fred Raab Joe Keefe Ernesto Ramirez JCVI Team Karen Nelson Shibu Yooseph Manolito Torralba SDSC Team Michael Norman Mahidhar Tatineni Robert Sinkovits UCSD Health Sciences Team William J. Sandborn Elisabeth Evans John Chang Brigid Boland David Brenner
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