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Dynamics of Your Gut Microbiome in Health and Disease


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Exponential Medicine
San Diego, CA
October 9, 2016

Published in: Data & Analytics
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Dynamics of Your Gut Microbiome in Health and Disease

  1. 1. “Dynamics of Your Gut Microbiome in Health and Disease” Presentation Exponential Medicine San Diego, CA October 9, 2016 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
  2. 2. There are 100 billion stars in the Andromeda galaxy… …and 100 billion galaxies in the known universe.
  3. 3. It’s a microbial world… …there are 100 million times as many bacteria on Earth as stars in the universe. Microbiology is the ultimate Big Data science!
  4. 4. Most of Life’s Evolutionary Time Was in the Microbial World You Are Here Source: Carl Woese, et al Tree of Life Derived from 16S rRNA Sequences
  5. 5. President Obama Announces National Microbiome Initiative May 13, 2016
  6. 6. Your Microbiome is Your “Near-Body” Environment The Microbiome Contains 300x as Many DNA Genes As Your Human DNA Inclusion of the “Dark Matter” of the Body Will Radically Alter Medicine
  7. 7. Your Gut Microbiome Contains Hundreds of Microbial Species Average Over 250 Healthy People From NIH Human Microbiome Project Note Log Scale Clostridium difficile Source: Weizhong Li, Andrew Prudomme, Larry Smarr, UCSD
  8. 8. Exploring the Gut Microbiome Time Series by Collaborating with the UCSD Knight Lab My Welcome Present to Rob
  9. 9. Mouth Stool Vagina Skin Source: Knight Lab, UCSD
  10. 10. Source: Knight Lab, UCSD
  11. 11. But Microbiome Time Series Are Very Different in Disease States
  12. 12. Fecal Transplants From Healthy Donor To C. Diff Patients Source: Knight Lab, UCSD
  13. 13. As a Model for the Precision Medicine Initiative, I Have Tracked My Internal Biomarkers To Understand My Body’s Dynamics My Quarterly Blood Draw Calit2 64 Megapixel VROOM
  14. 14. By Creating a Time Series of an Immune System Biomarker I Discovered I Had an Autoimmune Disease Normal Range <7.3 µg/mL 124x Upper Limit for Healthy Lactoferrin is a Protein Shed from Neutrophils - An Antibacterial that Sequesters Iron Typical Lactoferrin Value for Active Inflammatory Bowel Disease (IBD)
  15. 15. From a Time Series of My Gut Microbiome I Can Explain Changes in My Body Lialda & Uceris 12/1/13 to 1/1/14 12/1/13- 1/1/14 Frequent IBD Symptoms Weight Loss 7/1/12 to 12/1/14 Blue Balls on Diagram to the Right Principal Coordinate Analysis of Microbiome Ecology PCoA by Justine Debelius and Jose Navas, Knight Lab, UCSD Weight Data from Larry Smarr, Calit2, UCSD Weekly Weight Few IBD Symptoms Weight Gain 1/1/14 to 8/1/15 Red Balls on Diagram to the Right
  16. 16. From N=1 to a Population of People with Disease Inflammatory Bowel Disease Biobank For Healthy and Disease Patients Drs. William J. Sandborn, John Chang, & Brigid Boland UCSD School of Medicine, Division of Gastroenterology Over 300 Enrolled Announced November 7, 2014
  17. 17. Combining Deep Metagenomics and Supercomputing Time to Map the Differences Between Health and Disease • Controls: 100s of Healthy Subjects • Smarr Gut Microbiome Time Series – ~80 Samples Over 5 Years • Hundreds of IBD Patients – Phenotyped Patients Drawn from Sandborn BioBank Knight/Smarr Labs Using 100 CPU-Years of Supercomputer Time
  18. 18. Forty Years of Computing Gravitational Waves From Colliding Black Holes 1977 L. Smarr and K. Eppley Gravitational Radiation Computed from an Axisymmetric Black Hole Collision 2016 LIGO Consortium Spiral Black Hole Collision 40 Years
  19. 19. Complexity of Computing First Gut Microbiome Dynamics Versus First Dynamics of Colliding Black Holes • My 1975 PhD Dissertation – Solving Einstein’s Equations of General Relativity for Colliding Black Holes and Grav Waves – CDC 6600 Megaflop/s – Hundreds of Hours • Rob Knight and Smarr Gut Microbiome Map – Mapping From Illumina Sequencing to Taxonomy and Gene Abundance Dynamics – Comet Petaflop/s – Comet Core is 40,000x CDC6600 Speed – Million Core-Hours – 10,000x Supercomputer Time Gut Microbiome Takes ~ ½ Billion Times the Compute Power of Early Solutions of Dynamic General Relativity
  20. 20. The Future Foundation of Medicine is an Exponential Scaling-Up of the Number of Deeply Quantified Humans Source: @EricTopol Twitter 9/27/2014
  21. 21. Next Generation Telescopes Will Track Time Series of the Entire Universe On-Line in Five Years, Tracks Time Series of ~40B Objects, Creates 10M Alerts/Night Within 1 Minute of Observing 2x40Gbps NCSA Supercomputer