Presentation Exponential Medicine San Diego, CA October 9, 2016

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
http://lsmarr.calit2.net
1

2. There are 100 billion stars in the
Andromeda galaxy…
…and 100 billion galaxies in the
known universe.

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!

5. 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

6. President Obama Announces National Microbiome Initiative
May 13, 2016

7. 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

8. 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

9. Exploring the Gut Microbiome Time Series by
Collaborating with the UCSD Knight Lab
My Welcome Present to Rob

10. Mouth
Stool
Vagina
Skin
Source: Knight Lab, UCSD

11. Source: Knight Lab, UCSD

12. But Microbiome Time Series
Are Very Different in Disease States

14. Fecal Transplants
From Healthy Donor
To C. Diff Patients
Source: Knight Lab, UCSD

15. 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

16. 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)

17. 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

18. 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

19. 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

20. 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

21. 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

22. The Future Foundation of Medicine
is an Exponential Scaling-Up of the Number of Deeply Quantified Humans
Source: @EricTopol
Twitter 9/27/2014

23. 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