Deciphering the Dynamic Coupling of the Human Immune System and the Gut Microbiome

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This document discusses Dr. Larry Smarr's research into understanding the relationship between the human immune system and gut microbiome in Crohn's disease. Dr. Smarr sequenced his own genome to identify genetic polymorphisms associated with higher risk of Crohn's disease. He also conducted fine-time resolution sampling to study the distinct dynamics of the innate and adaptive immune system in health and disease. Additionally, he found major shifts in the gut microbiome between healthy individuals and those with two forms of inflammatory bowel disease.

Healthcare

“Deciphering the Dynamic Coupling of
the Human Immune System and the Gut Microbiome”
Overview
Data-Enabled Life Sciences Research (DELSA)
DELSA Workshop IV
Bethesda, MD
May 16, 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

Why Did I Have an Autoimmune Disease like IBD?
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
So I Set Out to Quantify All Three!
Paul B. Eckburg & David A. Relman
Clin Infect Dis. 44:256-262 (2007)

I Wondered if Crohn’s is an Autoimmune Disease,
Did I Have a Personal Genomic Polymorphism?
From www.23andme.com
SNPs Associated with CD
Polymorphism in
Interleukin-23 Receptor Gene
— 80% Higher Risk
of Pro-inflammatory
Immune Response
NOD2
ATG16L1
IRGM
Now Have My
Full Human Genome
Sequenced
Source: Larry Smarr, Calit2

Fine Time Resolution Sampling Reveals Distinct
Dynamics of Innate and Adaptive Immune System
Normal
Normal

We Find Major Shifts in Microbial Ecology
Between Healthy and Two Forms of IBD
Collapse of
Bacteroidetes
Explosion of
Proteobacteria
Source: Larry Smarr, Calit2

I Can Track Changes in My Microbiome Before and After
1 Month Antibiotic & 2 Month Prednisone Therapy
Therapy Greatly Reduced Two Phyla,
But Massive Reduction in Bacteroidetes
And Large % Proteobacteria Remain
Small Changes
With No Therapy
Reduced 45x
Reduced 90x
I am Trapped in a Local Ecological Equilibrium
“Far from Healthy”
Source: Larry Smarr, Calit2

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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 2019

Larry 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 Institutions

Larry 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 Systems

Larry 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.

Panel Discussion: Engaging underrepresented technologists, researchers, and e...

Larry Smarr

The Asia Pacific and Korea Research Platforms: An Overview Jeonghoon Moon

Larry 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 Institutions

Larry 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 Overview

Larry 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 Networks

Larry 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 Brown

Larry 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.

Built around answering questions

Larry Smarr

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.

Panel: NRP Science Impacts

Larry Smarr

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 Parashar

Larry 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 forward

Larry 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.

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How to effectively start market research in the health tech industry by defining objectives, crafting problem statements, selecting methods, identifying data collection sources, and setting clear timelines. This guide covers all the preliminary steps needed to lay a strong foundation for your research. "Market Research it too text-booky, I am in the market for a decade, I am living research book" this is what the founder I met on the event claimed, few of my colleagues rolled their eyes. Its true that one cannot over look the real life experience, but one cannot out beat structured gold mine of market research. Many 0 to 1 startup founders often overlook market research, but this critical step can make or break a venture, especially in health tech. But Why do they skip it? Limited resources—time, money, and manpower—are common culprits. "In fact, a survey by CB Insights found that 42% of startups fail due to no market need, which is like building a spaceship to Mars only to realise you forgot the fuel." Sudharsan Srinivasan Operational Partner Pitchworks VC Studio Overconfidence in their product’s success leads founders to assume it will naturally find its market, especially in health tech where patient needs, entire system issues and regulatory requirements are as complex as trying to perform brain surgery with a butter knife. Additionally, the pressure to launch quickly and the belief in their own intuition further contribute to this oversight. Yet, thorough market research in health tech could be the key to transforming a startup's vision into a life-saving reality, instead of a medical mishap waiting to happen. Example of Market Research working Innovaccer, founded by Abhinav Shashank in 2014, focuses on improving healthcare delivery through data-driven insights and interoperability solutions. Before launching their platform, Innovaccer conducted extensive market research to understand the challenges faced by healthcare organizations and the potential for innovation in healthcare IT. Identifying Pain Points: Innovaccer surveyed healthcare providers to understand their difficulties with data integration, care coordination, and patient engagement. They found widespread frustration with siloed systems and inefficient workflows. Competitive Analysis: Analyzed competitors offering similar solutions in healthcare analytics and interoperability. Identified gaps in comprehensive data aggregation, real-time analytics, and actionable insights. Regulatory Compliance: Ensured their platform complied with HIPAA and other healthcare data privacy regulations. This compliance was crucial to gaining trust from healthcare providers wary of data security issues. Customer Validation: Conducted pilot programs with several healthcare organizations to validate the platform's effectiveness in improving care outcomes and operational efficiency. Gathered feedback to refine features and user interface.

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1. “Deciphering the Dynamic Coupling of the Human Immune System and the Gut Microbiome” Overview Data-Enabled Life Sciences Research (DELSA) DELSA Workshop IV Bethesda, MD May 16, 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. Why Did I Have an Autoimmune Disease like IBD? 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 So I Set Out to Quantify All Three! Paul B. Eckburg & David A. Relman Clin Infect Dis. 44:256-262 (2007)

3. I Wondered if Crohn’s is an Autoimmune Disease, Did I Have a Personal Genomic Polymorphism? From www.23andme.com SNPs Associated with CD Polymorphism in Interleukin-23 Receptor Gene — 80% Higher Risk of Pro-inflammatory Immune Response NOD2 ATG16L1 IRGM Now Have My Full Human Genome Sequenced Source: Larry Smarr, Calit2

4. Fine Time Resolution Sampling Reveals Distinct Dynamics of Innate and Adaptive Immune System Normal Normal

5. We Find Major Shifts in Microbial Ecology Between Healthy and Two Forms of IBD Collapse of Bacteroidetes Explosion of Proteobacteria Source: Larry Smarr, Calit2

6. I Can Track Changes in My Microbiome Before and After 1 Month Antibiotic & 2 Month Prednisone Therapy Therapy Greatly Reduced Two Phyla, But Massive Reduction in Bacteroidetes And Large % Proteobacteria Remain Small Changes With No Therapy Reduced 45x Reduced 90x I am Trapped in a Local Ecological Equilibrium “Far from Healthy” Source: Larry Smarr, Calit2

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