This document summarizes a talk about research analyzing gut microbiome data from patients with autoimmune diseases and healthy subjects. The research used large memory high performance computing on the Gordon supercomputer to analyze over 1.2 trillion DNA bases of metagenomic sequencing data from the gut microbiomes. Analysis found major shifts in microbial ecology between healthy subjects and those with Crohn's disease or ulcerative colitis. Therapies for one subject's Crohn's disease reduced certain phyla but others remained at high levels. The research aims to develop noninvasive microbial diagnostics and new therapeutic tools for managing the microbiome.
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The Human Microbiome and the Revolution in Digital HealthLarry Smarr
2014.01.22
Calit2 Director Larry Smarr speaks as part of the Pensacola Evening Lecture Series, organized by the Florida Institute for Human and Machine Cognition, in Pensacola, FL.
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Attendees (and their microbes) at this event enjoyed a lively discussion on how we might better interact with our environment to support a healthier life for ourselves and our children. Think with your microbes about why we have to suffer from ever-increasing numbers of debilitating chronic diseases (asthma, food allergies, diabetes, autoimmune conditions, obesity, heart disease and cancer).
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Dr. Rodney Dietert is an internationally-known author, lecturer, scientist, book series editor, and educator. He is the author of Strategies for Protecting Your Child’s Immune System, and Science Sifting: Tools for Innovation in Science and Technology.
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This presentation on February 27, 2014 to NGS and the Future of Medicine at Illumina Headquarters in La Jolla, CA, was made by Calit2 Director Larry Smarr.
Quantifying Your Dynamic Human Body (Including Its Microbiome), Will Move Us ...Larry Smarr
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Observing the Dynamics of the Human Immune System Coupled to the Microbiome i...Larry Smarr
Calit2 Director Larry Smarr delivered this presentation to the CASIS Workshop on Biomedical Research Aboard the ISS at Columbia University in NY, NY, on May 28, 2014.
OMICS Publishing Group, Journal of Biological Systems- Open Access is an international, peer-reviewed journal overlays the development of new analytical methods or improvement of existing ones useful for the separation of even organic and inorganic components.
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Set of slides discussing the importance of microbes for human health. Made to accompany the hands-on activity "Modeling the Dynamic Digestive System Microbiome" published: http://www.asmscience.org/content/journal/jmbe/10.1128/jmbe.v16i2.908
Human nutrition, gut microbiome and immune system S'eclairer
Dr Zahida Chaudnary talks with the students about nutrition, gut microbiomes, and nutrition as we look at diseases and how your body reacts to what you eat.
Check out the slideshow by itself here.
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A review report on detailed study of research endeavours, undertaken on Human Microbiome, its composition, its implications, applications, disease and other role.
Human Microbiome is the current project in Research field. The importance of Microorganisms in the human body, the importance and novel roe of the microorganisms on a human body is very effective and helpful. Fecal Transplantation is a unique and helpful technique to cure a dreadful disease naturally by means of microorganisms or introducing the normal flora in to the body again.
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Large Memory High Performance ComputingEnables Comparison Across Human Gut Microbiomeof Patients with Autoimmune Diseasesand Healthy Subjects
1. “Large Memory High Performance Computing
Enables Comparison Across Human Gut Microbiome
of Patients with Autoimmune Diseases
and Healthy Subjects”
XSEDE 2013 – Gateway to Discovery
San Diego, CA
July 24, 2013
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. This Talk Based on XSEDE Selected Paper
Large Memory High Performance Computing
Enables Comparison Across Human Gut Microbiome
of Patients with Autoimmune Diseases
and Healthy Subjects
Sitao Wu, Weizhong Li, Larry Smarr,
UC San Diego (CRBS, Calit2)
Karen Nelson, Shibu Yooseph, Manolito Torralba
J. Craig Venter Institute, Rockville, MD
3. 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
I Arrived in La Jolla in 2000 After 20 Years in the Midwest
and Decided to Move Against the Obesity Trend
I Reversed My Body’s Decline By
Quantifying and Altering Nutrition and Exercise
http://lsmarr.calit2.net/repository/LS_reading_recommendations_FiRe_2011.pdf
4. Challenge-Develop Standards to Enable MashUps
of Personal Sensor Data Across Private Clouds
Withing/iPhone-
Blood Pressure
Zeo-Sleep
Azumio-Heart Rate
EM Wave PC-
Stress
MyFitnessPal-
Calories Ingested
FitBit -
Daily Steps &
Calories Burned
5. From One to a Billion Data Points Defining Me:
The Exponential Rise in Body Data in Just One Decade!
Billion: My Full DNA,
MRI/CT Images
Million: My DNA SNPs,
Zeo, FitBit
Hundred: My Blood VariablesOne:
My WeightWeight
Blood
Variables
SNPs
Microbial Genome
Improving Body
Discovering Disease
7. An MRI Shows Sigmoid Colon Wall Thickened
Indicating Probable Diagnosis of Crohn’s Disease
8. Your Body Has 10 Times
As Many Microbe Cells As Human Cells
Inclusion of the Microbiome
Will Radically Change Medicine
99% of Your
DNA Genes
Are in Microbe Cells
Not Human Cells
9. Quantifiying the Human Superorganism:
Distribution by Phyla of Microorganisms in Our Bodies
Nature Reviews
Microbiology
v.9, p. 279 (2011)
10. To Map My Gut Microbes, I Sent a Stool Sample to
the Venter Institute for Metagenomic Sequencing
Gel Image of Extract from Smarr Sample-Next is Library Construction
Manny Torralba, Project Lead - Human Genomic Medicine
J Craig Venter Institute
January 25, 2012
Shipped Stool Sample
December 28, 2011
I Received
a Disk Drive April 3, 2012
With Two 35 GB FASTQ Files
Weizhong Li, UCSD
NGS Pipeline:
230M Reads
Only 0.2% Human
Required 1/2 cpu-yr
Per Person Analyzed!
Sequencing
Funding
Provided by
UCSD School of
Health Sciences
11. June 8, 2012 June 14, 2012
Intense Scientific Research is Underway
on Understanding the Human Microbiome
From Culturing Bacteria to Sequencing Them
12. Additional Phenotypes Added from NIH HMP
For Comparative Analysis
5 Ileal Crohn’s, 3 Points in Time
6 Ulcerative Colitis, 1 Point in Time
35 “Healthy” Individuals
1 Point in Time
13. Gut Microbiome Metagenomic Datasets
One “Read” = 100 DNA Bases
Total of 1.2 Trillion Bases!
Source: Weizhong Li, CRBS, UCSD
15. Computing and Parallelization Requirements
of the Computational Tools in Our Workflow
Source: Weizhong Li, CRBS, UCSD
16. We Used SDSC’s Gordon Data-Intensive Supercomputer
to Analyze a Wide Range of Gut Microbiomes
• ~180,000 Core-Hrs on Gordon
– KEGG function annotation: 90,000 hrs
– Mapping: 36,000 hrs
– Used 16 Cores/Node
and up to 50 nodes
– Duplicates removal: 18,000 hrs
– Assembly: 18,000 hrs
– Other: 18,000 hrs
• Gordon RAM Required
– 64GB RAM for Reference DB
– 192GB RAM for Assembly
• Gordon Disk Required
– Ultra-Fast Disk Holds Ref DB for All Nodes
– 8TB for All Subjects
Enabled by
a Grant of Time
on Gordon from SDSC
Director Mike Norman
17. We Created a Reference Database
Of Known Gut Genomes
• NCBI 2012
– 2036 Complete + 1826 Draft Bacteria & Archaea Genomes
– 1397 Complete Virus Genomes
– 39 Complete Fungi Genomes
– 308 HMP Eukaryote Reference Genomes
• Total 5607 genomes, ~15 GB of sequences
Now to Align Our 12.5 Billion Reads
Against the Reference Database
Source: Weizhong Li, CRBS, UCSD
18. We Still Don’t Know a Significant
Fraction of the Gut Genomes
Source: Weizhong Li, CRBS, UCSD
19. Phyla Gut Microbial Abundance Without Viruses:
LS, Crohn’s, UC, and Healthy Subjects
Crohn’s Ulcerative
Colitis
HealthyLS
Toward Noninvasive
Microbial Ecology Diagnostics
Source: Weizhong Li, UCSD; Calit2 FuturePatient Expedition
20. We Find Major Shifts in Microbial Ecology
Between Healthy and Two Forms of IBD
Collapse of
Bacteroidetes
Explosion of
Proteobacteria
Microbiome “Dysbiosis”
or “Mass Extinction”?
On the IBD Spectrum
21. Major Changes in LS Microbiome Before and After
1 Month Antibiotic & 2 Month Prednisone Therapy
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?
22. 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.”