“observing the dynamics of the human immune system coupled to the microbiome in health and...
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“Observing the Dynamics of the Human Immune System Coupled to the Microbiome in Health and Disease”
CASIS Workshop on Biomedical Research Aboard the ISS
Columbia University
New York City, NY
May 28, 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
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Visualizing 5-10 Year Time Series of 150 Blood & Stool Variables Led Me to Discover a Chronic Disease
Calit2 64 megapixel VROOM
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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
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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
TypicalLactoferrin Value for
Active IBD
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The Natural Partner in the Oscillating Immune SystemWould Be The Gut Microbiome Ecology
Inclusion of the Microbiome Will Radically Change Medicine
99% of Your DNA Genes
Are in Microbe CellsNot Human Cells
Your Body Has 10 Times As Many Microbe Cells As Human Cells
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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 Microbiomesfrom 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 AbundanceRequired 25 CPU-Years at San Diego Supercomputer Center
Source: Jerry Sheehan, Calit2Weizhong Li, Sitao Wu, CRBS, UCSD
Total of 27 Billion ReadsOr 2.7 Trillion Bases
IBD Patients
250 Subjects1 Point in Time
Larry Smarr6 Points in Time
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Using Scalable Visualization Allows Comparison of the Relative Abundance of 200 Gut Microbe Species
Calit2 VROOM-FuturePatient Expedition
Comparing 3 LS Time Snapshots (Left) with Healthy, Crohn’s, UC (Right Top to Bottom)
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We Found Major Shifts in Microbial EcologyBetween Healthy and Two Forms of IBD
Collapse of Bacteroidetes
Explosion of Proteobacteria On the IBD Spectrum
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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
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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 MicrobiomeNow Possible Through Ubiome
Data source: LS (Yellow Lines Stool Samples); Sequencing and Analysis Ubiome
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What Might We Learn?Zero G as a Selection Pressure on Human Microbiome
Slide Presented by LS to NAC July 2013From NAC Information Technology Infrastructure Committee
"Space flight alters cellular and physiological responses in astronauts including the immune response,"
said ASU's Cheryl Nickerson, who led a project aboard NASA's space shuttle.
"However, relatively little was known about microbial changes to infectious disease risk
in response to space flight."