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The Digital Transformation of Healthcare


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

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

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  • 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. The Vision of Digitally Enabled Genomic Medicine is an Emerging Reality 2 July/August 2011 February 2012
  • 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. 100 Pioneer Wellness Project: Started March 2014 –I Am One of The 100 Source: Lee Hood, ISB
  • 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. Wireless Monitoring Helps Drive Exercise Goals
  • 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. From Measuring Macro-Variables to Measuring Your Internal Variables www.technologyreview.com/biomedicine/39636
  • 9. Visualizing Time Series of 150 LS Blood and Stool Variables, Each Over 5-10 Years Calit2 64 megapixel VROOM
  • 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. 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. Colonoscopy Images Show Inflamed Pseudopolyps in 6 inches of Sigmoid Colon Dec 2010 Jan 2012
  • 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. 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. 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. 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. Imagine Crowdsourcing 23andme SNPs For Even a Small Portion of Crohnology! www.crohnology.com
  • 18. Crowd-Sourcing the Effectiveness of Pharmaceutical Medications for Crohn’s Disease www.crohnology.com
  • 19. Treating the Human Superorganism: Your Body Has Ten Microbes for Every Human Cell! Nature Reviews Microbiology v.9, p. 279 (2011)
  • 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. 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. 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. 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. 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. Time Series Reveals Autoimmune Dynamics of Gut Microbiome by Phyla Therapy Six Metagenomic Time Samples Over 16 Months
  • 26. Toward Microbiome Disease Diagnosis UC 100x Healthy CD 100x Healthy
  • 27. Inexpensive 16S Time Series of Microbiome Now Possible Through Ubiome Data source: LS (Yellow Lines Stool Samples); Sequencing and Analysis Ubiome
  • 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. 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. 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. 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. Next Decade Will See New Microbiome “Gardening Tools” Journal of Nanotechnology (2012) August 7, 2012
  • 33. The Disruption of Consumer Health Data Gathering Is Growing Rapidly Blood Variable Time Series Stool Variable Time Series MicrobiomeTime SeriesHuman Genetic Variations
  • 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