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Genomics, Cellular Networks, Preventive Medicine, and Society


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Invited Talk
Guest Lecture to UCSD Medical and Pharmaceutical Students
Genetics in Medicine Course
Amphitheater of the Pharmaceutical Sciences Bldg
Title: Genomics, Cellular Networks, Preventive Medicine, and Society
La Jolla, CA

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Genomics, Cellular Networks, Preventive Medicine, and Society

  1. 1. Genomics, Cellular Networks, Preventive Medicine, and Society Guest Lecture to UCSD Medical and Pharmaceutical Students Genetics in Medicine Course Amphitheater of the Pharmaceutical Sciences Bldg December 11, 2009 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 Follow me on Twitter: lsmarr
  2. 2. The Digital Transformation of Health <ul><li>Wellness, Biomedical Informatics, and Preventive Medicine </li></ul><ul><ul><li>Data-Intensive Biomedical Cyberinfrastructure </li></ul></ul><ul><ul><li>Integrating Genomics, Proteomics, System Biology, and Disease States </li></ul></ul><ul><ul><li>Individualized Measurements Into Interoperable Informatics Systems </li></ul></ul><ul><ul><li>Population Health Systems </li></ul></ul><ul><ul><li>Wireless Behavioral Modification </li></ul></ul><ul><ul><li>Coupling Engineering and Medicine </li></ul></ul><ul><ul><ul><li>New Generation of Medical Devices </li></ul></ul></ul><ul><ul><ul><li>Innovations in MEMS and Nano </li></ul></ul></ul>
  3. 3. Leading Causes of Preventable Deaths in the United States in the year 2000 Mokdad AH, Marks JS, Stroup DF, Gerberding JL (March 2004). &quot;Actual causes of death in the United States, 2000&quot;. JAMA 291 (10): 1238–45. doi:10.1001/jama.291.10.1238. PMID 15010446. 1/3 of Deaths
  4. 4. Center for Wireless &Population Health Systems: Program on Research <ul><li>Wireless, Clinical, and Home Technologies to Measure and Improve Lifestyle and Other Health-Related Behaviors In: </li></ul><ul><ul><li>Healthy Adolescents </li></ul></ul><ul><ul><li>Adolescents Recovering from Leukemia </li></ul></ul><ul><ul><li>Adolescents Risk for Type 2 Diabetes </li></ul></ul><ul><ul><li>Young Adults to Prevent Weight Gain </li></ul></ul><ul><ul><li>Overweight and Obese Children and Adults </li></ul></ul><ul><ul><li>Depressed Adults </li></ul></ul><ul><ul><li>Post-Partum Women to Reduce Weight </li></ul></ul><ul><ul><li>Adults with Schizophrenia </li></ul></ul><ul><ul><li>Older Adults to Promote Successful Aging </li></ul></ul><ul><ul><li>Exposure Biology Research </li></ul></ul>
  5. 5. Center for Wireless &Population Health Systems Cross-Disciplinary Collaborating Investigators <ul><li>UCSD School of Medicine </li></ul><ul><ul><li>Kevin Patrick, MD, MS, Greg Norman, PhD, Fred Raab, Jacqueline Kerr, PhD </li></ul></ul><ul><ul><li>Jeannie Huang, MD, MPH </li></ul></ul><ul><li>UCSD Jacobs School of Engineering </li></ul><ul><ul><li>Bill Griswold, PhD, Ingolf Krueger, PhD, Tajana Simunic Rosing, PhD </li></ul></ul><ul><li>San Diego Supercomputer Center </li></ul><ul><ul><li>Chaitan Baru, PhD </li></ul></ul><ul><li>UCSD Department of Political Science </li></ul><ul><ul><li>James Fowler, PhD </li></ul></ul><ul><li>SDSU Departments of Psychology & Exercise/Nutrition Science </li></ul><ul><ul><li>James Sallis, PhD, Simon Marshall, PhD </li></ul></ul><ul><li>Santech, Inc. </li></ul><ul><ul><li>Sheri Thompson, PhD, Jennifer Shapiro, PhD, Ramesh Venkatraman, MS </li></ul></ul><ul><li>PhD students and Post-doctoral Fellows (current) </li></ul><ul><ul><li>Barry Demchak, Priti Aghera, Ernesto Ramirez, Laura Pina, Jordan Carlson </li></ul></ul>
  6. 6. Center for Wireless &Population Health Systems: Integrative View to Support Interventions Genetic & Biological Factors Interpersonal & Psychosocial Factors Environmental/Ecological Factors Medical & Exercise Sciences Behavioral & Social Sciences Environment, Population & Policy Sciences
  7. 7. Center for Wireless &Population Health Systems: Developing and Testing Engineering-Based Solutions Interpersonal & Psychosocial Factors NanoTech, Drug Delivery, Sensors, Body Area Networks (BANs) BAN-to-Mobile-to-Database, SMS/MMS Social networks Ubicomp, Location-Aware Services, Data Mining, Systems Sciences Genetic & Biological Factors Environmental/Ecological Factors
  8. 8. Center for Wireless &Population Health Systems: Mainly, It’s All About Sensors Psychological & Social sensors Biological sensors Diet & Physical Activity sensors Air quality (particulate, ozone, etc) Temperature, GPS, Sound, Video, Other devices & embedded sensors BP, Resp, HR, Blood (e.g. glucose, electrolytes, pharmacological, hormone), Transdermal, Implants Mood, Social network (peers/family) Attention, voice analysis Physical activity (PAEE, type), sedentary Posture/orientation, diet intake (photo/bar code) Wearable Environmental sensors Sensor data + Clinical & Personal Health Record Data + Ecological data on determinants of health + Analysis & comparison of parameters in near-real time (normative and ipsative) + Sufficient population-level data to comprehend trends, model them and predict health outcomes + Feedback in near real-time via SMS, audio, haptic or other cues for behavior or change in Rx device = True Preventive Medicine! Sensors embedded in the environment Geocoded data on safety, location of recreation, food, hazards, etc
  9. 9. Wireless Sensors Allow Your Body to Become an Internet Data Source <ul><li>Next Step—Putting You On-Line! </li></ul><ul><ul><li>Wireless Internet Transmission </li></ul></ul><ul><ul><li>Key Metabolic and Physical Variables </li></ul></ul><ul><ul><li>Model -- Dozens of 25 Processors and 60 Sensors / Actuators Inside of our Cars </li></ul></ul><ul><li>Post-Genomic Individualized Medicine </li></ul><ul><ul><li>Combine </li></ul></ul><ul><ul><ul><li>Genetic Code </li></ul></ul></ul><ul><ul><ul><li>Body Data Flow </li></ul></ul></ul><ul><ul><li>Use Powerful AI Data Mining Techniques </li></ul></ul>
  10. 10. The Impact on Personal Health from Nutrition, Exercise, Stress Management
  11. 11. Individual Health Requires Measurement of Your Body’s Performance
  12. 12. Measuring Key Molecules in the Blood Provides Longer Term Biofeedback Source: Ramesh Rao, Calit2
  13. 13. A Mobile Wireless System to Enhance Preventive Healthcare Source: Paul Blair, Calit2
  14. 14. A Calit2 Prototype of a SmartPhone Based System to Enhance Preventive Healthcare <ul><li>Diabetes </li></ul><ul><li>Congestive Heart Failure (CHF) </li></ul><ul><li>Cardiac </li></ul><ul><li>Hypertension </li></ul><ul><li>Asthmatics </li></ul><ul><li>Congestive Obstructive Pulmonary Disease(COPD) </li></ul><ul><li>Obesity </li></ul><ul><li>Infection </li></ul><ul><li>… Any chronic illness. </li></ul>Source: Paul Blair, Calit2 Calit2 Developed Bluetooth Sensors <ul><li>Blood Glucose </li></ul><ul><li>Body Weight and Blood Pressure </li></ul><ul><li>EKG / heart rhythms </li></ul><ul><li>BP (Blood Pressure) </li></ul><ul><li>Respiration </li></ul><ul><li>Respiration & Blood Oxygenation </li></ul><ul><li>Weight & Caloric intake </li></ul><ul><li>Temperature </li></ul><ul><li>Can be Easily Measured / Monitored, </li></ul><ul><li>and Therefore Controlled Before Effects are Catastrophic </li></ul>
  15. 15. NSF RESCUE Strongly Coupled with NIH WIISARD Grant W ireless I nternet I nformation S ystem for Medic a l R esponse in D isasters First Tier Mid Tier Wireless Networks Triage Command Center Reality Flythrough Mobile Video 802.11 pulse ox Calit2 is Working Closely with the First Responder Community
  16. 16. CitiSense: Air Pollution Case Study <ul><li>158 Million Live in Counties Violating Air Standards </li></ul><ul><ul><li>Cancer in Chula Vista, CA Increased 140/Million Residents </li></ul></ul><ul><ul><li>Largely Due to Diesel Trucks and Automobiles </li></ul></ul><ul><ul><ul><li>Particulates, Benzene, Sulfur Dioxide, Formaldehyde, etc. </li></ul></ul></ul><ul><li>30% of Public Schools Are Near Highways </li></ul><ul><ul><li>Asthma Rates 50% Higher There </li></ul></ul><ul><ul><li>350,000 – 1,300,000 Respiratory Events in Children Annually </li></ul></ul><ul><li>5 EPA Monitors in SD Co., 4000 Sq. Mi., 3.1M Residents </li></ul><ul><ul><li>But Air Pollution Not Uniformly Distributed in Space or Time </li></ul></ul><ul><ul><li>Hourly Updates to Web Page; Annual Reports in PDF Form </li></ul></ul><ul><li>Indoor Air Pollution is Uncharted Territory </li></ul><ul><ul><li>Second-hand Smoke is Major Concern </li></ul></ul><ul><ul><li>Also Mold, Radon </li></ul></ul>
  17. 17. CitiSense - Seacoast Sci. 4oz 30 compounds CitiSense Team PI: Bill Griswold Ingolf Krueger Tajana Simunic Rosing Sanjoy Dasgupta Hovav Shacham Kevin Patrick C/A L S W F CitiSense contribute distribute sense “ display” discover retrieve EPA Intel MSP
  18. 18. Lifechips--Merging Two Major Industries: Microelectronic Chips & Life Sciences LifeChips: the merging of two major industries, the microelectronic chip industry with the life science industry LifeChips medical devices 65 UCI Faculty
  19. 19. Calit2 Brings Computer Scientists and Engineers Together with Biomedical Researchers <ul><li>Some Areas of Concentration: </li></ul><ul><ul><li>Algorithmic and System Biology </li></ul></ul><ul><ul><li>Bioinformatics </li></ul></ul><ul><ul><li>Metagenomics </li></ul></ul><ul><ul><li>Cancer </li></ul></ul><ul><ul><li>Human Genomic Variation and Disease </li></ul></ul><ul><ul><li>Proteomics </li></ul></ul><ul><ul><li>Mitochondrial Evolution </li></ul></ul><ul><ul><li>Biomedical Instruments </li></ul></ul><ul><ul><li>Multi-Scale Cellular Imaging </li></ul></ul><ul><ul><li>Information Theory and Biological Systems </li></ul></ul><ul><ul><li>Telemedicine </li></ul></ul>UC Irvine UC Irvine Southern California Telemedicine Learning Center (TLC) National Biomedical Computation Resource an NIH supported resource center
  20. 20. Center for Algorithmic and Systems Biology@Calit2: Bringing World-Class Speakers to Conferences
  21. 21. Building a Genome-Scale Model of E. Coli in Silico <ul><li>E. Coli </li></ul><ul><ul><li>Has 4300 Genes </li></ul></ul><ul><ul><li>Model Has 2000! </li></ul></ul>Source: Bernhard Palsson UCSD Genetic Circuits Research Group JTB 2002 JBC 2002 <ul><li>in Silico Organisms Now Available 2007: </li></ul><ul><li>Escherichia coli </li></ul><ul><li>Haemophilus influenzae </li></ul><ul><li>Helicobacter pylori </li></ul><ul><li>Homo sapiens Build 1 </li></ul><ul><li>Human red blood cell </li></ul><ul><li>Human cardiac mitochondria </li></ul><ul><li>Methanosarcina barkeri </li></ul><ul><li>Mouse Cardiomyocyte </li></ul><ul><li>Mycobacterium tuberculosis </li></ul><ul><li>Saccharomyces cerevisiae </li></ul><ul><li>Staphylococcus aureus </li></ul>
  22. 22. Cytoscape: OPEN SOURCE Java Platform for Integration of Systems Biology Data <ul><li>Layout and Query of Interaction Networks (Physical And Genetic) </li></ul><ul><li>Visual and Programmatic Integration of Molecular State Data (Attributes) </li></ul><ul><li>Ultimate Goal is to Provide the Tools to Facilitate All Aspects of Pathway Assembly and Annotation </li></ul>
  23. 23. Research In The Ideker Lab Validation of Transcriptional Interactions With Causal or Functional Links Network Based Study of Disease Network Assembly from Genome-Scale Measurements Network Evolutionary Comparison / Cross-Species Alignment to Identify Conserved Modules Projection of Molecular Profiles on Protein Networks to Reveal Active Modules Alignment of Physical and Genetic Networks Network-Based Rationale Drug Design Network-Based Disease Diagnosis / Prognosis Moving from Genome-wide Association Studies (GWAS) to Network-wide “Pathway” Association (PAS)
  24. 25. Source: Lee Hood, ISB
  25. 26. Use Biology to Drive Technology and Computation. Need to Create a Cross-disciplinary Culture Source: Lee Hood, ISB
  26. 27. Disease Arises from Perturbed Cellular Networks: Dynamics of a Prion Perturbed Network in Mice Source: Lee Hood, ISB
  27. 28. Increasing Abundance of Protein A for Prion-Infected Blood Samples Source: Lee Hood, ISB
  28. 29. Organ-Specific Blood Proteins Will Make the Blood a Window into Health and Disease <ul><li>Perhaps 50 Major Organs or Cell Types </li></ul><ul><ul><li>Each Secreting Protein Blood Molecular Fingerprint </li></ul></ul><ul><li>The Levels of Each Protein in a Particular Blood Fingerprint Will Report the Status of that Organ </li></ul><ul><ul><li>Probably Need Perhaps 50 Organ-Specific Proteins Per Organ </li></ul></ul><ul><li>Will Need to Quantify 2500 Blood Proteins from a Drop of Blood </li></ul><ul><ul><li>Use Microfluidic/Nanotechnology Approaches </li></ul></ul>Key Point: Changes in The Levels Of Organ-Specific Markers Can Assess Virtually All Diseases Challenges for a Particular Organ Source: Lee Hood, ISB
  29. 30. Accelerator: The Perfect Storm-- Convergence of Engineering with Bio, Physics, & IT 2 mm HP MemorySpot Nanobio info technology 1000x Magnification MEMS 2 micron DNA-Conjugated Microbeads Human Adenovirus 400x Magnification NANO IBM Quantum Corral Iron Atoms on Copper 5 nanometers 400,000 x !
  30. 31. The Intersection of Solid State and Biological Information Systems Snail neuron grown on a CMOS chip with 128x128 Transistors. The electrical activity of the neuron is recorded by the chip. (Chip fabricated by Infineon Technologies)
  31. 32. A-D Research Foundation Nanotrope Separation Systems Technology ThermopeutiX
  32. 33. Nano-Structured Porous Silicon Applied to Cancer Treatment Michael J. Sailor Research Group Chemistry and Biochemistry Nanostructured “Mother Ships” for Delivery of Cancer Therapeutics Nanodevices for In-vivo Detection & Treatment of Cancerous Tumors
  33. 34. Challenge: What is the Appropriate Data Infrastructure for a 21 st Century Data-Intensive BioMedical Campus? <ul><li>Needed: a High Performance Biological Data Storage, Analysis, and Dissemination Cyberinfrastructure that Connects: </li></ul><ul><ul><li>Genomic and Metagenomic Sequences </li></ul></ul><ul><ul><li>MicroArrays </li></ul></ul><ul><ul><li>Proteomics </li></ul></ul><ul><ul><li>Cellular Pathways </li></ul></ul><ul><ul><li>Federated Repositories of Multi-Scale Images </li></ul></ul><ul><ul><ul><li>Full Body to Microscopy </li></ul></ul></ul><ul><li>With Interactive Remote Control of Scientific Instruments </li></ul><ul><li>Multi-level Storage and Scalable Computing </li></ul><ul><li>Scalable Laboratory Visualization and Analysis Facilities </li></ul><ul><li>High Definition Collaboration Facilities </li></ul>
  34. 35. Conceptual Architecture to Physically Connect Campus Resources Using Fiber Optic Networks UCSD Storage OptIPortal Research Cluster Digital Collections Manager PetaScale Data Analysis Facility HPC System Cluster Condo UC Grid Pilot Research Instrument N x 10Gbps Source:Phil Papadopoulos, SDSC/Calit2 DNA Arrays, Mass Spec., Microscopes, Genome Sequencers
  35. 36. UCSD Planned Optical Networked Biomedical Researchers and Instruments <ul><li>Connects at 10 Gbps : </li></ul><ul><ul><li>Microarrays </li></ul></ul><ul><ul><li>Genome Sequencers </li></ul></ul><ul><ul><li>Mass Spectrometry </li></ul></ul><ul><ul><li>Light and Electron Microscopes </li></ul></ul><ul><ul><li>Whole Body Imagers </li></ul></ul><ul><ul><li>Computing </li></ul></ul><ul><ul><li>Storage </li></ul></ul>UCSD Research Park Natural Sciences Building Creates Campus–Wide “ Data Utility” Cellular & Molecular Medicine West National Center for Microscopy & Imaging Biomedical Research Center for Molecular Genetics Pharmaceutical Sciences Building Cellular & Molecular Medicine East CryoElectron Microscopy Facility Radiology Imaging Lab Bioengineering [email_address] San Diego Supercomputer Center
  36. 37. Calit2 Microbial Metagenomics Cluster- Next Generation Optically Linked Science Data Server 512 Processors ~5 Teraflops ~ 200 Terabytes Storage 1GbE and 10GbE Switched/ Routed Core ~200TB Sun X4500 Storage 10GbE Source: Phil Papadopoulos, SDSC, Calit2
  37. 38. CAMERA’s Global Microbial Metagenomics CyberCommunity Over 3200 Registered Users From Over 70 Countries
  38. 39. The Human Microbiome is the Next Large NIH Drive to Understand Human Health and Disease <ul><li>“ A majority of the bacterial sequences corresponded to uncultivated species and novel microorganisms.” </li></ul><ul><li>“ We discovered significant inter-subject variability.” </li></ul><ul><li>“ Characterization of this immensely diverse ecosystem is the first step in elucidating its role in health and disease.” </li></ul>“ Diversity of the Human Intestinal Microbial Flora” Paul B. Eckburg, et al Science (10 June 2005) 395 Phylotypes
  39. 40. The Human Gut is a Microbial Environment Which is Being Metagenomically Sampled