Invited Presentation Microbiology and the Microbiome and the Implications for Human Health Analytic, Life Science & Diagnostic Association (ALDA) 2016 Senior Management Conference
Half Moon Bay, CA
October 3, 2016
Discovering the 100 Trillion Bacteria Living Within Each of UsLarry Smarr
This document provides a summary of a lecture on the human microbiome given by Dr. Larry Smarr. Some key points:
- The human microbiome refers to the trillions of bacteria that live within the human body. Each person contains 100 trillion bacteria, outnumbering human cells.
- Research into the microbiome is a rapidly growing field that provides insights into health and disease. The microbiome plays a role in processes like drug metabolism and immunity.
- The microbiome is established early in life and influenced by factors like birth method and antibiotic use in the first years. This early development can impact future health.
- Microbiome imbalances are linked to diseases like inflammatory bowel disease. New treatments are
Machine Learning Opportunities in the Explosion of Personalized Precision Med...Larry Smarr
This document summarizes a presentation given by Dr. Larry Smarr on machine learning opportunities in personalized precision medicine using massive datasets from individuals. Some key points:
- Smarr has tracked over 100 of his own blood biomarkers and microbiome over time, revealing health issues like chronic inflammation.
- Analysis of Smarr's microbiome alongside others revealed major shifts between healthy and disease states that can be classified using machine learning.
- Further analysis of microbial proteins identified which were over or under abundant in disease, helping characterize Smarr's own condition.
- Smarr's microbiome appeared to undergo an abrupt shift between two stable states correlated with a change in symptoms and drug therapy.
Fifty Years of Supercomputing: From Colliding Black Holes to Dynamic Microbio...Larry Smarr
This document provides a summary of a lecture given by Dr. Larry Smarr on the past, present, and future of supercomputing over the last 50 years. The summary discusses:
- How Smarr solved equations for colliding black holes in the 1970s using a megaFLOPs computer, whereas today collisions are detected using petaFLOPs supercomputers - a billion fold increase in speed.
- How Smarr's research has evolved from modeling astrophysical phenomena to mapping the human gut microbiome using terabytes of sequencing data and hundreds of thousands of core-hours of supercomputing.
- Emerging trends in brain-inspired computing architectures and non-von Neumann systems that are better suited to tasks
Stability in Health vs. Abrupt Changes in Disease in the Human Gut Microbiome...Larry Smarr
The document summarizes research on analyzing changes in human gut microbiome composition over time using 16S rRNA gene sequencing and the UniFrac metric. It presents findings that:
1) A healthy person's gut microbiome composition generally remains stable over periods of 60 days based on samples from multiple body sites.
2) In contrast, for people with C. difficile infections, their gut microbiome composition can abruptly shift to a healthy state within days after a fecal microbiota transplant from a healthy donor.
3) Analysis of one individual's gut microbiome samples over 3.5 years found the composition abruptly shifted between two distinct stable states that correlated with changes in symptoms and weight, before and after a
Linking Phenotype Changes to Internal/External Longitudinal Time Series in a ...Larry Smarr
This document summarizes Dr. Larry Smarr's presentation on quantifying physiological data from his own body over the past decade. Some key points:
- Smarr has gathered longitudinal time series data on over 200 biomarkers and microbiome samples to study phenotype changes from his autoimmune disease.
- Sensors have tracked daily metrics like weight, activity levels, and symptoms, revealing oscillations and episodes of inflammation.
- Imaging and biomarker analysis identified the specific location and nature of his Crohn's disease.
- Analysis of his microbiome samples over time uncovered a shift in microbial ecology that correlated with changes in drugs and symptoms.
- Expanding this type of personalized, quantitative approach could transform medicine by deeply characterizing individuals
Discovering the 100 Trillion Bacteria Living Within Each of UsLarry Smarr
This document provides a summary of a lecture on the human microbiome given by Dr. Larry Smarr. Some key points:
- The human microbiome refers to the trillions of bacteria that live within the human body. Each person contains 100 trillion bacteria, outnumbering human cells.
- Research into the microbiome is a rapidly growing field that provides insights into health and disease. The microbiome plays a role in processes like drug metabolism and immunity.
- The microbiome is established early in life and influenced by factors like birth method and antibiotic use in the first years. This early development can impact future health.
- Microbiome imbalances are linked to diseases like inflammatory bowel disease. New treatments are
Machine Learning Opportunities in the Explosion of Personalized Precision Med...Larry Smarr
This document summarizes a presentation given by Dr. Larry Smarr on machine learning opportunities in personalized precision medicine using massive datasets from individuals. Some key points:
- Smarr has tracked over 100 of his own blood biomarkers and microbiome over time, revealing health issues like chronic inflammation.
- Analysis of Smarr's microbiome alongside others revealed major shifts between healthy and disease states that can be classified using machine learning.
- Further analysis of microbial proteins identified which were over or under abundant in disease, helping characterize Smarr's own condition.
- Smarr's microbiome appeared to undergo an abrupt shift between two stable states correlated with a change in symptoms and drug therapy.
Fifty Years of Supercomputing: From Colliding Black Holes to Dynamic Microbio...Larry Smarr
This document provides a summary of a lecture given by Dr. Larry Smarr on the past, present, and future of supercomputing over the last 50 years. The summary discusses:
- How Smarr solved equations for colliding black holes in the 1970s using a megaFLOPs computer, whereas today collisions are detected using petaFLOPs supercomputers - a billion fold increase in speed.
- How Smarr's research has evolved from modeling astrophysical phenomena to mapping the human gut microbiome using terabytes of sequencing data and hundreds of thousands of core-hours of supercomputing.
- Emerging trends in brain-inspired computing architectures and non-von Neumann systems that are better suited to tasks
Stability in Health vs. Abrupt Changes in Disease in the Human Gut Microbiome...Larry Smarr
The document summarizes research on analyzing changes in human gut microbiome composition over time using 16S rRNA gene sequencing and the UniFrac metric. It presents findings that:
1) A healthy person's gut microbiome composition generally remains stable over periods of 60 days based on samples from multiple body sites.
2) In contrast, for people with C. difficile infections, their gut microbiome composition can abruptly shift to a healthy state within days after a fecal microbiota transplant from a healthy donor.
3) Analysis of one individual's gut microbiome samples over 3.5 years found the composition abruptly shifted between two distinct stable states that correlated with changes in symptoms and weight, before and after a
Linking Phenotype Changes to Internal/External Longitudinal Time Series in a ...Larry Smarr
This document summarizes Dr. Larry Smarr's presentation on quantifying physiological data from his own body over the past decade. Some key points:
- Smarr has gathered longitudinal time series data on over 200 biomarkers and microbiome samples to study phenotype changes from his autoimmune disease.
- Sensors have tracked daily metrics like weight, activity levels, and symptoms, revealing oscillations and episodes of inflammation.
- Imaging and biomarker analysis identified the specific location and nature of his Crohn's disease.
- Analysis of his microbiome samples over time uncovered a shift in microbial ecology that correlated with changes in drugs and symptoms.
- Expanding this type of personalized, quantitative approach could transform medicine by deeply characterizing individuals
The document discusses supercomputing analysis of the human microbiome. It describes how the human body hosts 100 trillion microorganisms containing 300 times as many genes as human DNA. Dr. Smarr has been collecting extensive personal health data over 7 years, including microbiome samples, to study the coupled immune-microbial system. Analyzing this data requires elaborate software running on high performance computers. The analysis can compare individuals with diseases to healthy populations and track disease progression over time.
Using Supercomputers and Gene Sequencers to Discover Your Inner MicrobiomeLarry Smarr
This keynote talk discusses research using supercomputers and gene sequencing to study the human microbiome. The human microbiome contains 100 trillion microorganisms and their genes outnumber human genes 300 to 1. The speaker has been collecting data from his own body over 7 years to study his microbiome and immune system interactions. Collaborating researchers have sequenced his gut microbiome over time as well as samples from autoimmune disease patients. Supercomputers are needed to analyze the massive amount of sequencing data and reveal details of microbial ecology and genetics in health and disease. Studying the human microbiome will revolutionize medicine in the next decade.
The Human Microbiome, Supercomputers,and the Advancement of MedicineLarry Smarr
The keynote presentation discusses the importance of the human microbiome and how understanding its dynamics can advance medicine. It notes that the human microbiome contains tens of trillions of microbial cells and hundreds of times as many genes as human cells. Understanding the microbiome as an ecology rather than focusing on single pathogens is crucial. The presentation describes research tracking one person's microbiome and biomarkers over time, finding shifts between healthy and diseased states. It advocates developing tools to manage the microbiome and new therapies like fecal transplants. National initiatives now recognize the microbiome's importance in health and disease.
This document discusses how advances in genetic sequencing and computing are enabling humans to read and understand the "software of life" encoded in their human and microbiome DNA. It notes that the human microbiome contains millions of microbial genes compared to the 23,000 genes in human cells. The author details how the cost of DNA sequencing has fallen over 100,000-fold, allowing sequencing of both human and microbial genomes. Machine learning will be needed to understand differences between healthy and diseased states by analyzing enormous genomic and microbiome datasets. The author provides an example of analyzing their own gut microbiome over time and comparing to healthy/IBD populations.
Dynamics of Your Gut Microbiome in Health and DiseaseLarry Smarr
This document summarizes a presentation by Dr. Larry Smarr on the dynamics of the gut microbiome in health and disease. It discusses how the gut microbiome contains hundreds of microbial species that vary significantly between healthy and diseased states. Dr. Smarr has tracked his own gut microbiome and biomarkers over time, discovering an autoimmune disease. He is now collaborating on a project combining deep metagenomic sequencing and supercomputing to map differences in the gut microbiome between healthy and inflammatory bowel disease patients.
Exploring Our Inner Universe Using Supercomputers and Gene SequencersLarry Smarr
This document summarizes a talk given by Dr. Larry Smarr on his research exploring the human microbiome using supercomputers and gene sequencers. He began by researching astrophysics but has recently applied those methods to study the microbes within the human body. Through deep genome sequencing of his own stool samples over time and large-scale computational analysis, he was able to map changes in his gut microbiome that provided insights into an undiagnosed autoimmune disease. His research demonstrates how quantitative analysis of the microbiome using advanced technologies can lead to new understandings of health and disease.
Exploring the Dynamics of The Microbiome in Health and DiseaseLarry Smarr
Remote Invited Provocateur Lecture
2017 Innovation Lab on Quantitative Approaches to Biomedical Data Science:
Challenges in our Understanding of the Microbiome
San Diego, CA
June 19, 2017
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.
How Studying Astrophysics and Coral Reefs Enabled Me to Become an Empowered,...Larry Smarr
This document summarizes Dr. Larry Smarr's talk on how his background in astrophysics and studying coral reefs enabled him to become an empowered patient by closely monitoring his gut microbiome. Some key findings from analyzing his stool samples over time included discovering oscillations in his immune system, invasions of opportunistic bacteria after disruptions, and evidence of chaos theory at play. Larger studies are now analyzing data from many individuals to better understand the dynamics of the human immune and microbiome systems.
Using Supercomputers to Discover the 100 Trillion Bacteria Living Within Each...Larry Smarr
This document summarizes a talk given by Dr. Larry Smarr on using supercomputers to analyze the human microbiome. It discusses how next-generation sequencing and analysis of microbial DNA reveals major differences between healthy and diseased gut microbiomes. Computational analysis of Smarr's own microbiome time series, in addition to data from hundreds of individuals, provides insights into inflammatory bowel disease. Large supercomputers and visualization resources were crucial for processing and comparing petabytes of sequencing data to advance understanding of microbiome dynamics and their links to human health and disease.
Assay Lab Within Your Body: Biometrics and BiomesLarry Smarr
This document summarizes a lecture about analyzing the human microbiome and its relationship to human health. It discusses how the human body contains 100 trillion microbial cells that contain 100 times as many genes as human DNA. Analysis of the speaker's own gut microbiome over time revealed changes in bacterial phyla between healthy and inflammatory bowel disease states. Collecting biomarkers from the speaker's body over years showed oscillations linked to gut microbes and immune response. Ongoing research aims to better understand dynamics of the human immune system and gut microbiome.
Quantfying Your Gut: A Personal JourneyLarry Smarr
Larry Smarr presented on his personal journey quantifying his gut health issues using advanced technology. He discovered through blood, stool, and MRI tests that he had severe colonic inflammation and Crohn's disease localized to his sigmoid colon. With the help of 3D organ segmentation and virtual reality, he was able to co-plan his successful sigmoid colon resection surgery. Longitudinal analysis of biomarkers and stool microbiome sequencing revealed shifts associated with his autoimmune condition and ties to mental health. Modulating the vagus nerve and microbiome offers possibilities for treating inflammation-related diseases.
Finding the Patterns in the Big Data From Human Microbiome EcologyLarry Smarr
This document summarizes a talk on analyzing human microbiome data to better understand health and disease. It discusses how sequencing and supercomputing is used to map microbial ecology in hundreds of people. Advanced analytics tools like Ayasdi are helping discover patterns separating healthy from disease states like inflammatory bowel disease. Future goals include applying these techniques to larger datasets and using molecular networks to better understand disease development at the genetic and protein level.
Big Data and Superorganism Genomics: Microbial Metagenomics Meets Human GenomicsLarry Smarr
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.
The Pacific Research Platform:a Science-Driven Big-Data Freeway SystemLarry Smarr
The Pacific Research Platform will create a regional "Big Data Freeway System" along the West Coast to support science. It will connect major research institutions with high-speed optical networks, allowing them to share vast amounts of data and computational resources. This will enable new forms of collaborative, data-intensive research for fields like particle physics, astronomy, biomedicine, and earth sciences. The first phase aims to establish a basic networked infrastructure, with later phases advancing capabilities to 100Gbps and beyond with security and distributed technologies.
The document discusses supercomputing analysis of the human microbiome. It describes how the human body hosts 100 trillion microorganisms containing 300 times as many genes as human DNA. Dr. Smarr has been collecting extensive personal health data over 7 years, including microbiome samples, to study the coupled immune-microbial system. Analyzing this data requires elaborate software running on high performance computers. The analysis can compare individuals with diseases to healthy populations and track disease progression over time.
Using Supercomputers and Gene Sequencers to Discover Your Inner MicrobiomeLarry Smarr
This keynote talk discusses research using supercomputers and gene sequencing to study the human microbiome. The human microbiome contains 100 trillion microorganisms and their genes outnumber human genes 300 to 1. The speaker has been collecting data from his own body over 7 years to study his microbiome and immune system interactions. Collaborating researchers have sequenced his gut microbiome over time as well as samples from autoimmune disease patients. Supercomputers are needed to analyze the massive amount of sequencing data and reveal details of microbial ecology and genetics in health and disease. Studying the human microbiome will revolutionize medicine in the next decade.
The Human Microbiome, Supercomputers,and the Advancement of MedicineLarry Smarr
The keynote presentation discusses the importance of the human microbiome and how understanding its dynamics can advance medicine. It notes that the human microbiome contains tens of trillions of microbial cells and hundreds of times as many genes as human cells. Understanding the microbiome as an ecology rather than focusing on single pathogens is crucial. The presentation describes research tracking one person's microbiome and biomarkers over time, finding shifts between healthy and diseased states. It advocates developing tools to manage the microbiome and new therapies like fecal transplants. National initiatives now recognize the microbiome's importance in health and disease.
This document discusses how advances in genetic sequencing and computing are enabling humans to read and understand the "software of life" encoded in their human and microbiome DNA. It notes that the human microbiome contains millions of microbial genes compared to the 23,000 genes in human cells. The author details how the cost of DNA sequencing has fallen over 100,000-fold, allowing sequencing of both human and microbial genomes. Machine learning will be needed to understand differences between healthy and diseased states by analyzing enormous genomic and microbiome datasets. The author provides an example of analyzing their own gut microbiome over time and comparing to healthy/IBD populations.
Dynamics of Your Gut Microbiome in Health and DiseaseLarry Smarr
This document summarizes a presentation by Dr. Larry Smarr on the dynamics of the gut microbiome in health and disease. It discusses how the gut microbiome contains hundreds of microbial species that vary significantly between healthy and diseased states. Dr. Smarr has tracked his own gut microbiome and biomarkers over time, discovering an autoimmune disease. He is now collaborating on a project combining deep metagenomic sequencing and supercomputing to map differences in the gut microbiome between healthy and inflammatory bowel disease patients.
Exploring Our Inner Universe Using Supercomputers and Gene SequencersLarry Smarr
This document summarizes a talk given by Dr. Larry Smarr on his research exploring the human microbiome using supercomputers and gene sequencers. He began by researching astrophysics but has recently applied those methods to study the microbes within the human body. Through deep genome sequencing of his own stool samples over time and large-scale computational analysis, he was able to map changes in his gut microbiome that provided insights into an undiagnosed autoimmune disease. His research demonstrates how quantitative analysis of the microbiome using advanced technologies can lead to new understandings of health and disease.
Exploring the Dynamics of The Microbiome in Health and DiseaseLarry Smarr
Remote Invited Provocateur Lecture
2017 Innovation Lab on Quantitative Approaches to Biomedical Data Science:
Challenges in our Understanding of the Microbiome
San Diego, CA
June 19, 2017
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.
How Studying Astrophysics and Coral Reefs Enabled Me to Become an Empowered,...Larry Smarr
This document summarizes Dr. Larry Smarr's talk on how his background in astrophysics and studying coral reefs enabled him to become an empowered patient by closely monitoring his gut microbiome. Some key findings from analyzing his stool samples over time included discovering oscillations in his immune system, invasions of opportunistic bacteria after disruptions, and evidence of chaos theory at play. Larger studies are now analyzing data from many individuals to better understand the dynamics of the human immune and microbiome systems.
Using Supercomputers to Discover the 100 Trillion Bacteria Living Within Each...Larry Smarr
This document summarizes a talk given by Dr. Larry Smarr on using supercomputers to analyze the human microbiome. It discusses how next-generation sequencing and analysis of microbial DNA reveals major differences between healthy and diseased gut microbiomes. Computational analysis of Smarr's own microbiome time series, in addition to data from hundreds of individuals, provides insights into inflammatory bowel disease. Large supercomputers and visualization resources were crucial for processing and comparing petabytes of sequencing data to advance understanding of microbiome dynamics and their links to human health and disease.
Assay Lab Within Your Body: Biometrics and BiomesLarry Smarr
This document summarizes a lecture about analyzing the human microbiome and its relationship to human health. It discusses how the human body contains 100 trillion microbial cells that contain 100 times as many genes as human DNA. Analysis of the speaker's own gut microbiome over time revealed changes in bacterial phyla between healthy and inflammatory bowel disease states. Collecting biomarkers from the speaker's body over years showed oscillations linked to gut microbes and immune response. Ongoing research aims to better understand dynamics of the human immune system and gut microbiome.
Quantfying Your Gut: A Personal JourneyLarry Smarr
Larry Smarr presented on his personal journey quantifying his gut health issues using advanced technology. He discovered through blood, stool, and MRI tests that he had severe colonic inflammation and Crohn's disease localized to his sigmoid colon. With the help of 3D organ segmentation and virtual reality, he was able to co-plan his successful sigmoid colon resection surgery. Longitudinal analysis of biomarkers and stool microbiome sequencing revealed shifts associated with his autoimmune condition and ties to mental health. Modulating the vagus nerve and microbiome offers possibilities for treating inflammation-related diseases.
Finding the Patterns in the Big Data From Human Microbiome EcologyLarry Smarr
This document summarizes a talk on analyzing human microbiome data to better understand health and disease. It discusses how sequencing and supercomputing is used to map microbial ecology in hundreds of people. Advanced analytics tools like Ayasdi are helping discover patterns separating healthy from disease states like inflammatory bowel disease. Future goals include applying these techniques to larger datasets and using molecular networks to better understand disease development at the genetic and protein level.
Big Data and Superorganism Genomics: Microbial Metagenomics Meets Human GenomicsLarry Smarr
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.
The Pacific Research Platform:a Science-Driven Big-Data Freeway SystemLarry Smarr
The Pacific Research Platform will create a regional "Big Data Freeway System" along the West Coast to support science. It will connect major research institutions with high-speed optical networks, allowing them to share vast amounts of data and computational resources. This will enable new forms of collaborative, data-intensive research for fields like particle physics, astronomy, biomedicine, and earth sciences. The first phase aims to establish a basic networked infrastructure, with later phases advancing capabilities to 100Gbps and beyond with security and distributed technologies.
The document summarizes the development of intestinal microbiota from infancy to adulthood. It describes how acquisition begins at birth and is influenced by maternal and environmental factors. The infant microbiota develops successively, influenced by factors like breastfeeding, antibiotics, and diet. During the first year, the microbiota plays a pivotal role in immune system maturation. In adulthood, the microbiota is impacted by lifestyle, medications, diet, stress, age, and living situation. Changes in the elderly microbiota can induce inflammation. Location of residence in the elderly is correlated with microbiota composition and health markers.
The document summarizes the results of analyzing changes in a person's gut microbiome before and after a 2-week backpacking trip in New Mexico. Some key findings include:
- The microbiome was overall pretty stable, with the main bacterial phyla composition not changing much.
- Certain genera like Faecalibacterium and Bacteroides decreased after the trip, while Blautia, Odoribacter, and Akkermansia increased.
- Microbial diversity was higher after the trip compared to previous tests, suggesting the trip helped diversity.
"In Gut We Trust" The Microbiome & WellbeingJoeFitAsia
The document discusses the microbiome, which refers to the microorganisms that live in and on the human body. It notes that the microbiome contains trillions of cells and plays an important role in human health and disease. Specifically, it affects body weight, nutrition absorption, and risk of chronic diseases. It also influences conditions like allergies, asthma, and the development of the immune system.
This document discusses the author's microbiome and how it changed over a one week period after tracking macronutrients and microbiome data. Key findings include an increase in certain bacteria like Roseburia, Faecalibacterium, and Bacteroides after one week. The author's diversity of phyla, classes, orders, families and genera decreased over this period, while the ratio of Bifido/Firmicutes increased. The document encourages readers to also track their microbiome over time to better understand changes.
Large Memory High Performance ComputingEnables Comparison Across Human Gut M...Larry Smarr
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.
Measuring the Human Brain-Gut Microbiome-Immune System Dynamics: a Big Data C...Larry Smarr
This document summarizes a talk given by Dr. Larry Smarr on measuring the human brain-gut microbiome-immune system dynamics and the challenges of analyzing big data related to these systems. It discusses how understanding the interactions between human genetics, behavior, and the human microbiome is important for understanding human health and disease. As an example, it details Dr. Smarr's own research into his Crohn's disease, analyzing his gut microbiome, immune markers, genetics, and symptoms over time. It shows how computational analysis of metagenomic sequencing data from many healthy and IBD patients can reveal differences in microbial ecology and gene families between health and disease states.
The document summarizes a seminar given by Dr. Larry Smarr on supercomputing the human microbiome. Some key points:
- The human microbiome contains 100 trillion microorganisms and their DNA contains 300 times as many genes as human DNA.
- Dr. Smarr has been collecting extensive data from his own body over 7 years to study his personal microbiome and immune system interactions using high performance computing.
- Analyzing microbiome data requires massive computing resources, such as millions of core hours on supercomputers. This reveals details of microbial ecology and genetics in health and disease.
- Computational analysis of microbiome sequencing data from many subjects shows major shifts in microbial populations between healthy and
Tracking Large Variations in My Immune Biomarkers and My Gut Microbiome: Infl...Larry Smarr
This document provides a 3-sentence summary of a presentation by Dr. Larry Smarr on tracking changes in his immune biomarkers and gut microbiome in relation to inflammation, Crohn's disease, and colon cancer:
Over the past decade, Dr. Smarr has quantified over a billion data points on his body through measures like blood tests, MRI/CT scans, and analysis of his gut microbiome, discovering through this data that he has episodic chronic inflammation and Crohn's disease affecting his colon. By comparing his biomarkers and symptoms over time and visualizing his microbiome ecology, Dr. Smarr has gained insights into the dynamics and invasiveness of species in his gut microbiome as it relates to his autoimmune
Ecological Disturbance of the Human Gut MicrobiomeAnne M. Estes
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
The document summarizes research on the gut microbiome and its relationship to obesity and non-alcoholic fatty liver disease (NAFLD). It reviews how the microbiome is influenced by factors from birth and can impact disease risk. Studies show differences in microbiome composition between obese, normal weight, and NAFLD patients, with NAFLD patients having higher levels of Escherichia bacteria that can produce alcohol. A pilot study found that treating pediatric NAFLD patients with the probiotic Lactobacillus GG for 8 weeks improved liver enzymes regardless of weight changes. Further research is still needed to fully understand the mechanisms and potential microbiome-based therapies.
The document discusses how probiotics and prebiotics can benefit gut health. It notes that the gut microbiome contains trillions of microbes that support immune function and nutrient production. Probiotics, like Bifidobacterium and Lactobacillus, found in foods like yogurt and kimchi, positively impact health by promoting a balanced microbiome and anti-inflammatory effects. Prebiotics are non-digestible fibers that feed beneficial bacteria and are found in foods such as onions, pistachios and oats. Consuming probiotics and prebiotics can help restore microbiome balance when disrupted by antibiotics and support immune health.
The document discusses the gut microbiota and its role in health and disease. In health, the gut microbiota forms a symbiotic relationship with the host, helping digest food, produce vitamins, and regulate the immune system. Dysbiosis, or an imbalance in the gut microbiota, is associated with various diseases like inflammatory bowel disease, irritable bowel syndrome, obesity, and cancer. The gut microbiota influences disease by affecting barrier function, immune activation, and chronic inflammation.
This document analyzes the relationship between food and the intestinal microbiota in humans. It discusses what intestinal microbiomes are, their roles, and their relationship with the host. The document explores how diet can modulate gut microbiome composition and influence enterotypes. It summarizes research studies that link long-term diet to enterotypes and show the gut microbiome of malnourished children remains immature. The conclusion is that food affects the gut flora, which in turn impacts health and development.
From Quantified Self to Quantified SurgeryLarry Smarr
Larry Smarr underwent surgery to remove his diseased sigmoid colon. He used self-quantification of biomarkers over a decade to diagnose chronic inflammation. Pre-surgical planning used 3D imaging from MRI converted to VR. During surgery, 3D organ segmentation guided the surgical team and EGG monitored recovery. Post-surgery, biomarkers like CRP and microbiome returned to healthy levels, showing the benefits of a quantified approach to surgery.
Systems Nutrition of the Gut-Liver Axis and the Role of the MicrobiomeNorwich Research Park
This document summarizes a presentation on systems nutrition and the role of the gut-liver axis and microbiome. It discusses how the small intestine plays a key role in early pro-inflammatory disturbances by affecting the gut microbiota and their metabolites. The gut microbiota influences the intestinal and systemic metabolome and host metabolic regulation through transcription factors like PPARγ, FXR, and AHR. Beneficial bacteria like Akkermansia muciniphila may lose benefits under certain dietary conditions like heme. Targeting the small intestine and microbiota with foods, bioactives, probiotics or drugs could improve gut and liver health.
The document discusses the human microbiome, which refers to the trillions of microorganisms that inhabit various parts of the human body. It notes that the microbiome contains over 100 trillion bacterial cells and has more genes than the human genome. The largest and most dense microbiome is located in the gut, where microbes help break down nutrients and support human metabolism. While microbiome compositions vary between individuals and change over time, they perform similar important functions for human health.
The document discusses the gut microbiota. It states that the gut contains trillions of microbes including bacteria, archaea, fungi and viruses. These microbes help digest food, harvest energy, regulate the immune system and prevent diseases like IBS and cancer. Techniques to study the gut microbiota include culturing, PCR, fluorescence in situ hybridization and direct sequencing of the 16S rRNA gene. Pyrosequencing provides high throughput sequencing of the 16S rRNA gene and allows identification of unknown bacterial species. Stool samples are commonly used to study the gut microbiota as they are easier to collect than biopsy samples.
Know Thyself: Quantifying Your Human Body and Its One Hundred Trillion MicrobesLarry Smarr
Understanding Cultures and Addressing Disparities in Society: Degrees of Health and Well-Being Public Lecture Series
University of California, San Diego
January 20, 2016
Capturing the Interactive Dynamics of the Human Host/Microbiome SystemLarry Smarr
1) Dr. Larry Smarr reported on results from a decade of self-quantification, including longitudinal measurements of his gut microbiome and over 100 biomarkers, to better understand the interactive dynamics of the human-microbiome system in health and disease.
2) Analysis found that Smarr's gut microbiome was unstable with high levels of E. coli, unlike healthy individuals, and computational analysis linked this dysbiosis to chronic inflammation identified in his biomarkers.
3) Smarr underwent robotic colon resection surgery in 2016, and analysis found his gut microbiome changed more dramatically after surgery than from colonoscopy or typical differences between individuals, eventually achieving a healthy post-surgical state.
Assay Lab Within Your Body: Biometrics and BiomesLarry Smarr
This document summarizes a lecture about analyzing the human microbiome and its relationship to human health. It discusses how the human body contains 100 trillion microbial cells that contain 100 times as many genes as human DNA. Recent advances now allow sequencing these microbial genomes and analyzing massive datasets to map the dynamics of the immune-microbial system and its connection to disease states. A key focus is generating high-resolution time series data of the gut microbiome and immune variables from large cohorts to understand how they influence conditions like inflammatory bowel disease. There is potential to design gut microbes as sensors of disease states by programming them to detect specific conditions.
Individual, Consumer-Driven Care of the Future: Taking Wellness One Step FurtherLarry Smarr
Calit2 Director Larry Smarr gives the closing keynote address to the 2nd annual Learning Conference on Integrated Delivery Systems in San Diego on May 7, 2014.
From Me To We: Discovering the Trillions of Microorganisms That are a Part of UsLarry Smarr
The document summarizes a lecture about the human microbiome and its importance in health and disease. It discusses how sequencing DNA has revealed that the human body hosts trillions of microorganisms and that 99% of our genes are microbial. Understanding the microbiome is crucial for medicine as shifts in the microbial ecology can be linked to various diseases. The lecturer discusses his own efforts to track biomarkers and microbiome data over time, revealing how perturbations correlated with disease symptoms and weight changes. Precision approaches analyzing large cohorts will be needed to unravel microbiome dynamics in health and illness.
2014.02.06
Calit2 Director Larry Smarr lecture to the Osher Lifelong Learning Institute as part of the Winter 2014 Qualcomm Institute lecture series for Osher.
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.
This document summarizes a lecture given by Dr. Larry Smarr on exploring the human microbiome. In 3 sentences:
Dr. Smarr discussed how recent advances in sequencing have revealed that the human body hosts trillions of microbes containing many times more genes than human cells. Longitudinal studies of his own biomarkers and microbiome provided insights into the dynamics of his autoimmune disease. New research is exploring the complex relationships between the gut microbiome and various health conditions.
Using Genetic Sequencing to Unravel the Dynamics of Your Superorganism BodyLarry Smarr
The document summarizes a talk given by Dr. Larry Smarr on his research tracking extensive health data on himself over many years. Some key points:
1) Smarr collected over a billion data points defining his body, including DNA sequencing, medical images, and daily biomarkers, revealing episodic inflammation related to his Crohn's disease.
2) Analysis of his gut microbiome via metagenomic sequencing showed many typically abundant bacterial species were severely depleted compared to healthy individuals.
3) Tracking changes over time demonstrated the coupled dynamics of his immune system and gut microbiome in response to therapies, similar to ecological models of invasive species dominating after natives are disturbed.
The quantified self movement has grown from a niche hobby to an emerging industry as self-tracking of health metrics has become mainstream. Consumer use of fitness trackers, sleep monitors, and calorie counters has exploded, with leading companies attracting significant funding. The presenter used personal sensors to track various biomarkers and drive health behavior changes. New integrated dashboards combine data from devices, medical records, and genetics to provide personalized health coaching. The self-monitoring business is undergoing consolidation as large companies acquire startups. Healthcare systems will need to integrate high volumes of personal health data from consumers. The presenter's own data revealed previously undiagnosed chronic inflammation, and analysis of microbiome time series provided new insights into inflammatory bowel disease
Will the Quantified Self Movement Disrupt Healthcare?Larry Smarr
Calit2 Director Larry Smarr delivers an invited talk to the Pre-Biotechnology Industry Organization International Convention Symposium in San Diego, Calif., on June 22, 2014.
My Remembrances of Mike Norman Over The Last 45 YearsLarry Smarr
Mike Norman has been a leader in computational astrophysics for over 45 years. Some of his influential work includes:
- Cosmic jet simulations in the early 1980s which helped explain phenomena from galactic centers.
- Pioneering the use of adaptive mesh refinement in the 1990s to achieve dynamic load balancing on supercomputers.
- Massive cosmology simulations in the late 2000s with over 100 trillion particles using thousands of processors across multiple supercomputing sites, producing petabytes of data.
- Developing end-to-end workflows in the 2000s to couple supercomputers, high-speed networks, and large visualization systems to enable real-time analysis of extremely large astrophysics simulations.
Metagenics How Do I Quantify My Body and Try to Improve its Health? June 18 2019Larry Smarr
Larry Smarr discusses quantifying his body and health over time through extensive self-tracking. He measures various biomarkers through regular blood tests and analyzes his gut microbiome by sequencing stool samples. This revealed issues like chronic inflammation and an unhealthy microbiome. Smarr then took steps like a restricted eating window and increasing plant diversity in his diet, which reversed metabolic syndrome issues and correlated with shifts in his microbiome ecology. His goal is to continue precisely measuring factors like toxins, hormones, gut permeability and food/supplement impacts to further optimize his health.
Panel: Reaching More Minority Serving InstitutionsLarry Smarr
This document discusses engaging more minority serving institutions (MSIs) in cyberinfrastructure development through regional networks. It provides data showing the importance of MSIs like historically black colleges and universities (HBCUs) in educating underrepresented minority students in STEM fields. Regional networks can help equalize opportunities by assisting MSIs in overcoming barriers to resources through training, networking infrastructure support, and helping institutions obtain necessary staffing and funding. Strategies mentioned include collaborating with MSIs on grants and addressing issues identified in surveys like lack of vision for data use beyond compliance. The goal is to broaden participation in STEAM fields by leveraging the success MSIs have shown in supporting underrepresented students.
Global Network Advancement Group - Next Generation Network-Integrated SystemsLarry Smarr
This document summarizes a presentation on global petascale to exascale workflows for data intensive sciences. It discusses a partnership convened by the GNA-G Data Intensive Sciences Working Group with the mission of meeting challenges faced by data-intensive science programs. Cornerstone concepts that will be demonstrated include integrated network and site resource management, model-driven frameworks for resource orchestration, end-to-end monitoring with machine learning-optimized data transfers, and integrating Qualcomm's GradientGraph with network services to optimize applications and science workflows.
Wireless FasterData and Distributed Open Compute Opportunities and (some) Us...Larry Smarr
This document discusses opportunities for ESnet to support wireless edge computing through developing a strategy around self-guided field laboratories (SGFL). It outlines several potential science use cases that could benefit from wireless and distributed computing capabilities, both in the short term through technologies like 5G, LoRa and Starlink, and longer term through the vision of automated SGFL. The document proposes some initial ideas for deploying and testing wireless edge computing technologies through existing projects to help enable the SGFL vision and further scientific opportunities. It emphasizes that exploring these emerging areas could help drive new science possibilities if done at a reasonable scale.
The Asia Pacific and Korea Research Platforms: An Overview Jeonghoon MoonLarry Smarr
This document provides an overview of Asia Pacific and Korea research platforms. It discusses the Asia Pacific Research Platform working group in APAN, including its objectives to promote HPC ecosystems and engage members. It describes the Asi@Connect project which provides high-capacity internet connectivity for research across Asia-Pacific. It also discusses the Korea Research Platform and efforts to expand it to 25 national research institutes in Korea. New related projects on smart hospitals, agriculture, and environment are mentioned. The conclusion discusses enhancing APAN and the Korea Research Platform and expanding into new areas like disaster and AI education.
Panel: Reaching More Minority Serving InstitutionsLarry Smarr
This document discusses engaging more minority serving institutions (MSIs) in the National Research Platform (NRP). It provides data showing that MSIs serve a disproportionate number of underrepresented minority students and are important producers of STEM graduates from these groups. The NRP can help broaden participation in STEAM fields by providing MSIs access to advanced cyberinfrastructure resources, new learning modalities, and opportunities for collaborative research between MSIs and other institutions. Regional networks also have a role to play in helping MSIs overcome barriers and attracting them to collaborative grants. The goal is to tear down walls between research and teaching and reinvent the university experience for more inclusive learning and innovation.
Panel: The Global Research Platform: An OverviewLarry Smarr
The document provides an overview of the Global Research Platform (GRP), an international collaborative partnership creating a distributed environment for data-intensive global science. The GRP facilitates high-performance data gathering, analytics, transport up to terabits per second, computing, and storage to support large-scale global science cyberinfrastructure ecosystems. It aims to orchestrate research across multiple domains using international testbeds for investigating new technologies related to data-intensive science. Examples of instruments generating exabytes of data that would benefit include the Korea Superconducting Tokamak, the High Luminosity LHC, genomics, the SKA radio telescope, and the Vera Rubin Observatory.
Panel: Future Wireless Extensions of Regional Optical NetworksLarry Smarr
CENIC is a non-profit organization that operates an 8,000+ mile fiber optic network connecting over 12,000 sites across California, including K-12 schools, universities, libraries, and research organizations. It has over 750 private sector partners and contributes over $100 million annually to the California economy. CENIC's network enables research and education collaborations, innovation, and economic growth statewide. It also operates a wireless research network called PRP that connects wireless sensors to supercomputers, supporting applications like wildfire modeling.
Global Research Platform Workshops - Maxine BrownLarry Smarr
The document announces a workshop on global research platforms that will be held virtually in 2021 and in Salt Lake City in 2022, with topics including large-scale science, next-generation platforms, data transport, and international testbeds. It also announces the 4th Global Research Platform Workshop to be held in October 2023 in Limassol, Cyprus co-located with the IEEE eScience 2023 conference.
EPOC and NetSage provide engagement and network monitoring services to support research and education. NetSage collects anonymized network flow data to help understand traffic patterns and troubleshoot performance issues. It provides dashboards and analysis to answer common questions from network engineers and end users. Examples of NetSage deployments and use cases were shown for the CENIC network, including top sources and destinations of traffic, debugging slow flows, and analyzing international traffic patterns by country over time.
The document discusses accelerating science discovery with AI inference-as-a-service. It describes showcases using this approach for high energy physics and gravitational wave experiments. It outlines the vision of the A3D3 institute to unite domain scientists, computer scientists, and engineers to achieve real-time AI and transform science. Examples are provided of using AI inference-as-a-service to accelerate workflows for CMS, ProtoDUNE, LIGO, and other experiments.
Democratizing Science through Cyberinfrastructure - Manish ParasharLarry Smarr
This document summarizes a presentation by Manish Parashar on democratizing science through cyberinfrastructure. The key points are:
1) Broad, fair, and equitable access to advanced cyberinfrastructure is essential for democratizing 21st century science, but there are significant barriers related to knowledge, technical issues, social factors, and balancing capabilities.
2) An advanced cyberinfrastructure ecosystem for all requires integrated portals, access to local and national resources through high-speed networks, diverse allocation modes, embedded expertise networks, and broad training.
3) Realizing this vision will require a scalable federated ecosystem with diverse capabilities and incentives for partnerships to meet growing needs for cyberinfrastructure and
Panel: Building the NRP Ecosystem with the Regional Networks on their Campuses;Larry Smarr
This document summarizes a panel discussion on building the National Research Platform ecosystem with regional networks. The panelists discussed how their regional networks are connecting to and using the Nautilus nodes of the NRP. Examples included using NRP for deep learning and computer vision research at the University of Missouri, challenges of adoption in Nevada and potential solutions, and Georgia Tech's new involvement through the Southern Crossroads regional network. The regional networks see opportunities to expand NRP access and training to enable more researchers in their regions to take advantage of the platform.
Open Force Field: Scavenging pre-emptible CPU hours* in the age of COVID - Je...Larry Smarr
The document discusses Open Force Field (OpenFF), an open-source project that enables rapid development of molecular force fields through automated infrastructure, open data and software, and an open science approach. OpenFF provides access to large quantum chemical datasets, runs quantum chemistry calculations on pre-emptible cloud resources with minimal human intervention, and facilitates easy iteration and testing of new force field hypotheses through an open development model.
Panel: Open Infrastructure for an Open Society: OSG, Commercial Clouds, and B...Larry Smarr
The document discusses open infrastructure for an open society and the role of commercial clouds. It describes how the National Research Platform (NRP), Open Science Grid (OSG), and Open Science Data Federation (OSDF) provide open infrastructure through open source components that anyone can contribute to and use. It then discusses how Southwestern Oklahoma State University leveraged NRP resources on their campus and engaged students and local teachers. Finally, it outlines the pros and cons of commercial clouds, when they may be suitable to use, and how tools like CloudBank and Kubernetes can help facilitate science users' access to cloud resources.
Panel: Open Infrastructure for an Open Society: OSG, Commercial Clouds, and B...Larry Smarr
The document discusses open infrastructure for an open society and the role of commercial clouds. It describes how the National Research Platform (NRP), Open Science Grid (OSG), and Open Science Data Federation (OSDF) provide open infrastructure through open source components that anyone can contribute to and use. It then discusses how Southwestern Oklahoma State University leveraged NRP resources on their campus and engaged students and local teachers. Finally, it outlines the pros and cons of commercial clouds, noting they provide huge capacity and variety but are very expensive for regular use. Facilitating science users on clouds requires services like CloudBank and Kubernetes federation.
Panel: Open Infrastructure for an Open Society: OSG, Commercial Clouds, and B...Larry Smarr
The document discusses open infrastructure for an open society and the role of commercial clouds. It describes how the National Research Platform (NRP), Open Science Grid (OSG), and Open Science Data Federation (OSDF) provide open infrastructure through open source components that anyone can contribute to and use. It then discusses how Southwestern Oklahoma State University leveraged NRP resources on their campus and engaged students and local teachers. Finally, it outlines the pros and cons of commercial clouds, noting they provide huge capacity and variety but are very expensive for regular use. Facilitating science users on clouds requires tools for account management, documentation, and integrating cloud resources through HTCondor and Kubernetes.
Frank Würthwein - NRP and the Path forwardLarry Smarr
NRP will replace PRP and aims to democratize access to national research cyberinfrastructure. The long term vision is to create an open national cyberinfrastructure by federating resources across research institutions. Key innovations include an innovative network fabric, application libraries for FPGAs, a "bring your own resource" model, and innovative scheduling and data infrastructure. The NSF has funded the Prototype National Research Platform project to support NRP for the next 5 years. NRP aims to grow resources, introduce new capabilities, and be driven by the research community.
Generative Classifiers: Classifying with Bayesian decision theory, Bayes’ rule, Naïve Bayes classifier.
Discriminative Classifiers: Logistic Regression, Decision Trees: Training and Visualizing a Decision Tree, Making Predictions, Estimating Class Probabilities, The CART Training Algorithm, Attribute selection measures- Gini impurity; Entropy, Regularization Hyperparameters, Regression Trees, Linear Support vector machines.
Discovering Digital Process Twins for What-if Analysis: a Process Mining Appr...Marlon Dumas
This webinar discusses the limitations of traditional approaches for business process simulation based on had-crafted model with restrictive assumptions. It shows how process mining techniques can be assembled together to discover high-fidelity digital twins of end-to-end processes from event data.
We are pleased to share with you the latest VCOSA statistical report on the cotton and yarn industry for the month of March 2024.
Starting from January 2024, the full weekly and monthly reports will only be available for free to VCOSA members. To access the complete weekly report with figures, charts, and detailed analysis of the cotton fiber market in the past week, interested parties are kindly requested to contact VCOSA to subscribe to the newsletter.
Quantifying Your Dynamic Human Body (Including Its Microbiome), Will Move Us From a Sickcare System to a Healthcare System
1. “Quantifying Your Dynamic Human Body
(Including Its Microbiome), Will Move Us
From a Sickcare System to a Healthcare System”
Invited Presentation
Microbiology and the Microbiome and the Implications for Human Health
Analytic, Life Science & Diagnostic Association (ALDA) 2016 Senior Management Conference
Half Moon Bay, CA
October 3, 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. Conference Abstract
“For the past several years, Dr. Smarr has been engaged in a computer-aided study of his
body. Larry has been charting his bodily input and output, as well as taking periodic blood
and stool tests for five years as part of a new generation of medical research that is
focusing on early detection of disease states. Studying the microbiome is part of this
area of medical research since there are 100 times as many genes on the microbial DNA
as your human DNA and yet this is currently outside of medical practice. Larry believes
that over the next 10-20 years efforts like his will enable scientists to create computational
models of your body, grounded in you and your microbiome's genome, and—using
longitudinal time series of data refreshed continually with measurements from your body
and collated with similar readings from millions of other similarly monitored bodies.
Mining this enormous database, software will produce detailed guidance about diet,
supplements, exercise, medication, or treatment—guidance based on a precise reading of
your own body’s peculiarities and its status in real time. And, at that time, says Larry, you
will have a scientific basis for medicine and the current US "Sickcare" system will be
replaced by a true "Healthcare" system.
3. From One to a Trillion Data Points Defining Me in 15 Years:
The Exponential Rise in Body Data
Weight
Blood Biomarker
Time Series
Human Genome
SNPs
Microbiome Metagenomic
Time Series
Improving Body
Discovering Disease
Human Genome
Genomics Big Data Tsunami
Imagine Following
A Hundred Million
Quantified People
4. Calit2 Has Been Had a Vision of
“the Digital Transformation of Health” for 15 Years
• Next Step—Putting You On-Line!
– Wireless Internet Transmission
– Key Metabolic and Physical Variables
– Model -- Dozens of Processors and 60 Sensors /
Actuators Inside of our Cars
• Post-Genomic Individualized Medicine
– Combine
–Genetic Code
–Body Data Flow
– Use Powerful AI Data Mining Techniques
www.bodymedia.com
The Content of This Slide from 2001 Larry Smarr
Calit2 Talk on Digitally Enabled Genomic Medicine
5. Over the Last Decade, I Have Used a Variety of Personal Sensors
To Quantify My Body & Drive Behavioral Change
Withings/iPhone-
Blood Pressure
Zeo-Sleep
Azumio-Heart Rate
MyFitnessPal-
Calories Ingested
FitBit -
Daily Steps &
Calories Burned
Withings WiFi Scale -
Daily Weight
6. Wireless Monitoring
Produced Time Series That Helped Me Improve My Health
Since Starting November 3, 2011
Total Distance Tracked 6180 miles = Round Trip San Diego to Nome, Alaska
Total Vertical Distance Climbed 190,000 ft. = 6.5x Mt. Everest
My Resting Heartrate
Fell from 70 to 40!
Elliptical
Walking
Sunday January 17, 2016
137
42
I Increased
Walking,
Aerobic, and
Resistance
Training,
All of Which
Have Health
Benefits
8. 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
9. Only One of My Blood Measurements
Was Far Out of Range
Complex Reactive Protein (CRP) is a Blood Biomarker
for Detecting Presence of Inflammation
Doctor:
“Come Back When You Have a Symptom”
Normal Range <1 mg/L
10. First Peak Was an Early Warning Sign
of Developing Internal Disease State
Normal Range <1 mg/L
27x Upper Limit
Complex Reactive Protein (CRP) is a Blood Biomarker
for Detecting Presence of Inflammation
Episodic Peaks in Inflammation
Followed by Spontaneous Drops
11. Longitudinal Time Series Revealed
Oscillatory Behavior in an Immune Variable That is Antibacterial
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)
12. Time Series Reveals Oscillations in Immune Biomarkers
Associated with Time Progression of Autoimmune Disease
Immune &
Inflammation
Variables
Weekly
Symptoms
Pharma
Therapies
Stool
Samples
2009 20142013201220112010 2015
Monitoring Your Body
Would Have Suggested
Intervention Now!
13. Descending Colon
Sigmoid Colon
Threading Iliac Arteries
Major Kink
Confirming the IBD (Colonic 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
Transverse Colon
Liver
Small Intestine
Diseased Sigmoid Colon
Cross Section
MRI Jan 2012
Severe Colon
Wall Swelling
14. Why Did I Have an Autoimmune Disease
like Crohn’s Disease?
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)
I Have Been Quantifying All Three
15. I Found I Had One of the Earliest Known SNPs
Associated with Crohn’s Disease
From www.23andme.com
SNPs Associated with CD
Polymorphism in
Interleukin-23 Receptor Gene
— 80% Higher Risk
of Pro-inflammatory
Immune Response
NOD2
IRGM
ATG16L1
16. There May Be a Correlation Between CD SNPs
and Where and When the Disease Manifests
Me-Male
CD Onset
At 60-Years Old
Il-23R
Rs1004819
1.8x Increased Risk
Female
CD Onset
At 20-Years Old
NOD2 (1)
Rs2066844
2.08x Increased Risk
Subject with
Ileal Crohn’s
Subject with
Colonic Crohn’s
Source: Larry Smarr and 23andme
17. IBD is a “Spectrum” Disorder Stratified by a Personal Combination
of the 163 Known SNP Loci Associated with IBD
The width of the bar is proportional to the variance explained by that locus
“Host–microbe interactions have shaped the genetic architecture
of inflammatory bowel disease,” Jostins, et al. Nature 491, 119-124 (2012)
23andme Has Collected
10,000 IBD Patient’s SNPs
18. Using Supercomputers and Deep Metagenomics
to Discover the Shifts in Microbiome Ecology in Health and Disease
19. An Initial Study of the Variation of the Human Gut Microbiome
Across Populations and Within an Individual Over Time
5 Ileal Crohn’s Patients,
3 Points in Time
2 Ulcerative Colitis Patients,
6 Points in Time
“Healthy” Individuals
Larry Smarr, Weizhong Li, Sitao Wu, UCSD
Graphic Source: Jerry Sheehan, Calit2
Total of 27 Billion Reads
Or 2.7 Trillion Bases
Inflammatory Bowel Disease (IBD) Patients
250 Subjects
1 Point in Time
7 Points in Time
Each Sample Has 100-200 Million Illumina Short Reads (100 bases)
Larry Smarr
(Colonic Crohn’s)
20. To Map Out the Dynamics of Autoimmune Microbiome Ecology
Couples Next Generation Genome Sequencers to Big Data Supercomputers
Source: Weizhong Li, UCSD
Our Team Used 25 CPU-years
to Compute
Comparative Gut Microbiomes
Starting From
2.7 Trillion DNA Bases
of My Samples
and Healthy and IBD Subjects
Illumina HiSeq 2000 at JCVI
SDSC Gordon Data Supercomputer
21. The Supercomputer Converts Tens of Billions of DNA Fragments
Into Relative Abundance of Hundreds of Microbial Species
Average Over 250 Healthy People
From NIH Human Microbiome Project
Note Log Scale
Clostridium difficile
22. We Found Major State Shifts in Microbial Ecology Phyla
Between Healthy and Two Forms of IBD
Most
Common
Microbial
Phyla
Average HE
Average Ulcerative Colitis
Average LS
Colonic Crohn’s
Average Ileal Crohn’s
Collapse of Bacteroidetes
Great Increase in Actinobacteria
Explosion of
Proteobacteria
Hybrid of UC and CD
High Level of Archaea
23. Metagenomic Sequencing the Stool of 300 Patients
Sorted Out Their Health or Disease Type
Source: Thomas Hill, Ph.D.
Executive Director Analytics
Dell | Information Management Group, Dell Software
Healthy
Ulcerative Colitis
Colonic Crohn’s
Ileal Crohn’s
25. The Human Gut
as a Super-Evolutionary Microbial Cauldron
• Enormous Density
– 1000x Ocean Water
• Highly Dynamic Microbial Ecology
– Hundreds to Thousands of Species
• Horizontal Gene Transfer
• Phages
• Adaptive Selection Pressures (Immune System)
– Innate Immune System
– Adaptive Immune System
– Macrophages and Antimicrobial proteins
• Constantly Changing Environmental Pressures
– Diet
– Antibiotics
– Pharmaceuticals
26. Time Series Reveals Autoimmune Dynamics
of Gut Microbiome by Phyla
Therapy
Six Metagenomic Time Samples Over 16 Months
27. Lessons From Ecological Dynamics I:
Invasive Species Dominate After Major Species Destroyed
”In many areas following these burns
invasive species are able to establish themselves,
crowding out native species.”
Source: Ponderosa Pine Fire Ecology
http://cpluhna.nau.edu/Biota/ponderosafire.htm
28. Almost All Abundant Species (≥1%) in Healthy Subjects
Are Severely Depleted in Larry’s Gut Microbiome
29. Invasive Species Take Over Gut Microbiome
in Disease State
152x
765x
148x
849x
483x
220x
201x
522x
169x
20 Most Abundant Species
Source: Sequencing JCVI; Analysis Weizhong Li, UCSD
LS December 28, 2011 Stool Sample
Relative Abundance
In Gut Microbiome
30. Lessons from Ecological Dynamics II:
Gut Microbiome Has Multiple Relatively Stable Equilibria
“The Application of Ecological Theory Toward an Understanding of the Human Microbiome,”
Elizabeth Costello, Keaton Stagaman, Les Dethlefsen, Brendan Bohannan, David Relman
Science 336, 1255-62 (2012)
31. We are Genomically Analyzing My Stool Time Series
in a Collaboration with the UCSD Knight Lab
Larry’s 40 Stool Samples Over 3.5 Years
to Rob’s lab on April 30, 2015
32. LS Weekly Weight During Period of 16S Microbiome Analysis
Abrupt Change in Weight and in Symptoms at January 1, 2014
Lialda
Uceris
Frequent IBD Symptoms
Weight Loss
Few IBD Symptoms
Weight Gain
Source: Larry Smarr, UCSD
34. Coloring Samples Before (Blue) and After (Red) January 2014
Reveals Clustering
Source Justine Debelius, Knight Lab, UC San Diego
35. An Apparent Sudden Phase Change Occurs
Source Justine Debelius, Knight Lab, UC San Diego
36. My Gut Microbiome Ecology Shifted After Drug Therapy
Between Two Time-Stable Equilibriums Correlated to Physical Symptoms
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
37. My Fasting Glucose Level
Seems to Have Also Shifted in January 2014
Glucose Best Range
70 to 100
Prediabetes Range
100 to 125
Weight gain started
38. 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
39. To Expand IBD Project the Knight/Smarr Labs Were Awarded
~ 1 CPU-Century Supercomputing Time
• Smarr Gut Microbiome Time Series
– From 7 Samples Over 1.5 Years
– To 50 Samples Over 4 Years
• IBD Patients: From 5 Crohn’s Disease and 2 Ulcerative Colitis
Patients to ~100 Patients
– 50 Carefully Phenotyped Patients Drawn from Sandborn BioBank
– 43 Metagenomes from the RISK Cohort of Newly Diagnosed IBD patients
• New Software Suite from Knight Lab
– Re-annotation of Reference Genomes, Functional / Taxonomic Variations
– Novel Compute-Intensive Assembly Algorithms from Pavel Pevzner
8x Compute Resources
Over Prior Study
N=1 Microbiome Time Series Compared to Populations of Healthy and Sick
Using Machine Learning and Data Analytics
41. Forty Years of Computing Gravitational Waves From Colliding Black Holes –
One Billion Times Increase in Supercomputer Speed!
1977
L. Smarr and K. Eppley
Gravitational Radiation Computed
from an Axisymmetric
Black Hole Collision
40 Years
2016
LIGO Consortium
Spiral Black Hole Collision
MegaFLOPS PetaFLOPS
Holst, et al. Bull. Amer. Math. Soc 53, 513-554 (1916)
42. 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
– Hundred Hours of Computing
• Rob Knight & Smarr Gut Microbiome Map Using 800,000 Core-Hours on SDSC’s Comet
– 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
43. NCSA Numerical Astrophysics Group
Used NCSA Supercomputers to Explain Cosmic Phenomena
Mike Norman, Charles Evans, Roger Ove, John Hawley,
Dean Sumi, Rob Wolff, Larry Smarr
Gas Accretion Onto a Black Hole
Creates “Exhaust Channels”
Cosmic Jets
Emerge from
Galactic Centers
Collision of Neutron Stars
44. “A Whole-Cell Computational Model
Predicts Phenotype from Genotype”
A model of
Mycoplasma genitalium,
• 525 genes
• Using 1,900
experimental
observations
• From 900 studies,
• They created the
software model,
• Which requires 128
computers to run
45. Early Attempts at Modeling the Systems Biology of
the Gut Microbiome and the Human Immune System
47. The Transformation in Automobile Healthcare
Gives Us Insight into the Human Healthcare Shift to Come
http://onlinelibrary.wiley.com/doi/10.1002/biot.201100495/abstract
48. Modern Cars Have Massive Sensor Arrays Which Record Time Series
Enabling Computer Diagnostics For Early Warning
http://blog.asautoparts.com/5-common-symptoms-of-faulty-car-sensors/
Before the computer
diagnostics technology,
most car owners
did not know
something was wrong
with the engine
until something
drastic happened,
such as overheating or
running out of gas.
www.thepeoplehistory.com/carelectronics.html
49. The Transition from Car “Sickcare” to Car “Healthcare”
Was Enabled by Pattern Recognition Using Big Data Analytics
“… using IBM big data and analytics technology,
all available data sources can be analyzed
to discover patterns and anomalies
to predict and anticipate maintenance needs.
50. From Reactive Repairs for “Chronic Disease”
to Quantified Cars That “Keep Themselves Healthy”
“In the not-too-distant future, analytics will help organizations
prevent incidents from occurring,
rather than just being a tool to rapidly react to incidents.”
--Rich Radi, director, Driver Excellence for ARI, the world’s largest
privately held family-owned fleet management company
51. The Planetary Computer Fed by a Trillion Sensors
Will Drive a Global Industrial Internet
www.tsensorssummit.org
www-bsac.eecs.berkeley.edu/frontpagefiles/BSACGrowingMEMS_Markets_%20SEMI.ORG.html
Next Decade
One Trillion
GE’s Industrial Internet is Currently
Generating 10,000 TB/Day
54. Next Generation Telescopes
Will Keep Track of the Entire Universe
On-Line in Five Years,
Tracks ~40B Objects,
Creates 10M Alerts/Night
Within 1 Minute of Observing
2x40Gbps
NCSA Supercomputer
55. Artificial Intelligence (AI) is Advancing at a Amazing Pace:
Deep Learning Algorithms Working on Massive Datasets
Training on 30M Moves,
Then Playing Against Itself
Less Than
2 Years!
56. From Self-Driving Cars to Personalized Medical Assistants
Deep Learning Will Provide Artificial Intelligence to Coach Us to Wellness
Where Medicine Coaching is Now
Where Wellness Coaching is Going
January 10, 2014
57. Can a Planetary Supercomputer with Artificial Intelligence
Transform Our Sickcare System to a Healthcare System?
Using this data, the planetary computer will be able
to build a computational model of your body
and compare your sensor stream with millions of others.
Besides providing early detection of internal changes
that could lead to disease,
cloud-powered voice-recognition wellness coaches
could provide continual personalized support on lifestyle
choices, potentially staving off disease
and making health care affordable for everyone.
ESSAY
An Evolution Toward a Programmable
Universe
By LARRY SMARR
Published: December 5, 2011
58. Thanks to Our Great Team!
Calit2@UCSD
Future Patient Team
Jerry Sheehan
Tom DeFanti
Joe Keefe
John Graham
Kevin Patrick
Mehrdad Yazdani
Jurgen Schulze
Andrew Prudhomme
Philip Weber
Fred Raab
Ernesto Ramirez
JCVI Team
Karen Nelson
Shibu Yooseph
Manolito Torralba
Ayasdi
Devi Ramanan
Pek Lum
UCSD Metagenomics Team
Weizhong Li
Sitao Wu
SDSC Team
Michael Norman
Mahidhar Tatineni
Robert Sinkovits
UCSD Health Sciences Team
David Brenner
Rob Knight Lab
Justine Debelius
Jose Navas
Gail Ackermann
Greg Humphrey
William J. Sandborn Lab
Elisabeth Evans
John Chang
Brigid Boland
Dell/R Systems
Brian Kucic
John Thompson