“The Digital Transformation
of Healthcare”
Guest Lecture
Pharmacy Informatics 2014
University of California San Diego
June...
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
Converging Megatrends
Driving the Tran...
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” It
Using Nutrition and Exercise, I Became Healthier
2000
Age
41
2010
Age
61...
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 Sleep
Mine is Betw...
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 Up...
But by Using Stool Analysis Time Series, I Discovered
I Had Oscillating Immune Variables Far Above Normal
Normal Range
<7....
Colonoscopy Images Show
Inflamed Pseudopolyps in 6 inches of Sigmoid Colon
Dec 2010 Jan 2012
Descending Colon
Sigmoid Colon
Threading Iliac Arteries
Major Kink
Confirming the IBD (Crohn’s) Hypothesis:
Finding the “S...
Why Did I Have an Autoimmune Disease like IBD?
Despite decades of research,
the etiology of Crohn's disease
remains unknow...
The Cost of Sequencing a Megabase of DNA
Has Fallen Over 10,000x in the Last Ten Years!
This Has Enabled Sequencing of
Bot...
I Wondered if Crohn’s is an Autoimmune Disease,
Did I Have a Personal Genomic Polymorphism?
From www.23andme.com
SNPs Asso...
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...
To Map Out the Dynamics of My Microbiome Ecology
I Partnered with the J. Craig Venter Institute
• JCVI Did Metagenomic
Seq...
We Downloaded Additional Gut Microbiomes
from NIH HMP For Comparative Analysis
5 Ileal Crohn’s Patients,
3 Points in Time
...
We Found Major Shifts in Microbial Ecology
Between Healthy and Two Forms of IBD
Collapse of
Bacteroidetes
Explosion of
Pro...
Tracking How 1 Month Antibiotic, 2 Months Prednisone Therapy
Alters the Gut Microbial Ecology
Reduced 45x
Reduced 90x
Ther...
Comparing Changes in Gut Microbiome Ecology with
Oscillations of the Innate and Adaptive Immune System
Normal
Innate Immun...
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);
Sequen...
From War to Gardening:
New Therapeutical Tools for Managing the Microbiome
“I would like to lose the language of warfare,”...
Evidence for the Efficacy of Probiotics is IBD is Mixed -
More Clinical Research Needed
“...there is virtually no evidence...
From the Single “Bad” Microbe Medical Target
to the Microbiome Ecology Paradigm
Sci Transl Med 4, 137rv5 (2012);
Science 3...
Microbiome Transfer
May Be a Radical New Treatment for IBD
www.gihealthfoundation.org/reuters/articles.cfm?article=2011110...
Next Decade Will See New Microbiome
“Gardening Tools”
Journal of Nanotechnology (2012)
August 7, 2012
The Disruption of Consumer Health Data Gathering
Is Growing Rapidly
Blood Variable Time Series Stool Variable Time Series
...
Thanks to Our Great Team!
UCSD Metagenomics Team
Weizhong Li
Sitao Wu
Calit2@UCSD
Future Patient Team
Jerry Sheehan
Tom De...
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The Digital Transformation of Healthcare

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Calit2 Director Larry Smarr's presentation to pharmacy students at the Skaggs School on June 2, 2014.

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The Digital Transformation of Healthcare

  1. 1. “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
  2. 2. The Vision of Digitally Enabled Genomic Medicine is an Emerging Reality 2 July/August 2011 February 2012
  3. 3. 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 Revolution Big Data Source: Lee Hood, ISB
  4. 4. 100 Pioneer Wellness Project: Started March 2014 –I Am One of The 100 Source: Lee Hood, ISB
  5. 5. 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 How Did I Get Started? I Arrived in La Jolla in 2000 and 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
  6. 6. Wireless Monitoring Helps Drive Exercise Goals
  7. 7. Quantifying My Sleep Pattern Using a Zeo - Increased My Average to 8 Hours/Night REM is Normally 20% of Sleep Mine 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
  8. 8. From Measuring Macro-Variables to Measuring Your Internal Variables www.technologyreview.com/biomedicine/39636
  9. 9. Visualizing Time Series of 150 LS Blood and Stool Variables, Each Over 5-10 Years Calit2 64 megapixel VROOM
  10. 10. 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
  11. 11. 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 Typical Lactoferrin Value for Active IBD
  12. 12. Colonoscopy Images Show Inflamed Pseudopolyps in 6 inches of Sigmoid Colon Dec 2010 Jan 2012
  13. 13. Descending Colon Sigmoid Colon Threading 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 Colon Liver Small Intestine Diseased Sigmoid Colon Cross Section MRI Jan 2012
  14. 14. 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)  So I Set Out to Quantify All Three!
  15. 15. 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
  16. 16. 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-inflammatory Immune Response NOD2 ATG16L1 IRGM I am Now an Advisor on the 23andme IBD Project
  17. 17. Imagine Crowdsourcing 23andme SNPs For Even a Small Portion of Crohnology! www.crohnology.com
  18. 18. Crowd-Sourcing the Effectiveness of Pharmaceutical Medications for Crohn’s Disease www.crohnology.com
  19. 19. Treating the Human Superorganism: Your Body Has Ten Microbes for Every Human Cell! Nature Reviews Microbiology v.9, p. 279 (2011)
  20. 20. 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
  21. 21. We Downloaded Additional Gut Microbiomes from 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 Abundance Required 25 CPU-Years at San Diego Supercomputer Center Source: Jerry Sheehan, Calit2 Weizhong Li, Sitao Wu, CRBS, UCSD Total of 27 Billion Reads Or 2.7 Trillion Bases IBD Patients 250 Subjects 1 Point in Time Larry Smarr 6 Points in Time
  22. 22. We Found Major Shifts in Microbial Ecology Between Healthy and Two Forms of IBD Collapse of Bacteroidetes Explosion of Proteobacteria On the IBD Spectrum
  23. 23. 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?
  24. 24. 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
  25. 25. Time Series Reveals Autoimmune Dynamics of Gut Microbiome by Phyla Therapy Six Metagenomic Time Samples Over 16 Months
  26. 26. Toward Microbiome Disease Diagnosis UC 100x Healthy CD 100x Healthy
  27. 27. Inexpensive 16S Time Series of Microbiome Now Possible Through Ubiome Data source: LS (Yellow Lines Stool Samples); Sequencing and Analysis Ubiome
  28. 28. 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.”
  29. 29. 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.”
  30. 30. 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
  31. 31. Microbiome Transfer May Be a Radical New Treatment for IBD www.gihealthfoundation.org/reuters/articles.cfm?article=20111102drgd011 Dr. Alexander Khoruts, NY Times www.nytimes.com/2010/07/13/science/13micro.html Not FDA Approved Yet; Increasing Number of Doctors Performing Procedure; Clinical Trials Under Way; Encouraging Results… Procedures Starting With Natural Microbiome Next Steps: Create Synthetic Microbiomes Tuned to the Patient See Microbiome 1:3 (2013)
  32. 32. Next Decade Will See New Microbiome “Gardening Tools” Journal of Nanotechnology (2012) August 7, 2012
  33. 33. The Disruption of Consumer Health Data Gathering Is Growing Rapidly Blood Variable Time Series Stool Variable Time Series MicrobiomeTime SeriesHuman Genetic Variations
  34. 34. 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 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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