1. “Building an Information Infrastructure to Support Microbial Metagenomic Sciences"
Presentation for the Microbe Project Interagency Team [
UCSD
La Jolla, CA
January 14, 2006
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

2. 1200 Researchers in Two Buildings
Calit2 Brings Computer Scientists and Engineers Together with Biomedical Researchers
Some Areas of Concentration:
Metagenomics
Genomic Analysis of Organisms
Evolution of Genomes
Cancer Genomics
Human Genomic Variation and Disease
Mitochondrial Evolution
Proteomics
Computational Biology
Information Theory and Biological Systems
UC Irvine
UC San Diego
1200 Researchers in Two Buildings

3. PI Larry Smarr

4. Announcing Tuesday January 17, 2006

5. The Sargasso Sea Experiment The Power of Environmental Metagenomics
Yielded a Total of Over 1 billion Base Pairs of Non-Redundant Sequence
Displayed the Gene Content, Diversity, & Relative Abundance of the Organisms
Sequences from at Least 1800 Genomic Species, including 148 Previously Unknown
Identified over 1.2 Million Unknown Genes
J. Craig Venter, et al.
Science
2 April 2004:
Vol. 304. pp
MODIS-Aqua satellite image of ocean chlorophyll in the Sargasso Sea grid about the BATS site from 22 February 2003

6. CAMERA will include All Sorcerer II Metagenomic Data
Marine Genome Sequencing Project Measuring the Genetic Diversity of Ocean Microbes
CAMERA will include All Sorcerer II Metagenomic Data

7. Much of Genome Work Has Occurred in Animals
Evolution is the Principle of Biological Systems: Most of Evolutionary Time Was in the Microbial World
You Are Here
Much of Genome Work Has Occurred in Animals
Source: Carl Woese, et al

8. Major New Science Challenge: Understanding the Transition from Collective to Species Evolution
“Bacteria naturally reside in communities, in ecosystems. It is hard to find a bacterial niche that does not comprise hundreds or thousands of different species, all interacting in intricate delicate ways, to make a fascinatingly complex and stable whole.”
“In an era of rampant horizontal gene transfer, organismal evolution would be basically collective. It is the community of organisms that evolves, not the various individual organismal types.”
“This shift from a primitive genetic free-for-all to modern organisms must by all account have been one of the most profound happenings in the whole of evolutionary history.”
--Carl Woese , Evolving Biological Organization in Microbial Phylogeny and Evolution, ed. Jan Sapp (2005)

9. GenBank Protein Data Bank
Genomic Data Is Growing Rapidly, But Metagenomics Will Vastly Increase The Scale…
100 Billion Bases!
35,000 Structures
GenBank
Protein Data Bank
Total Data < 1TB

10. Metagenomics Will Couple to Earth Observations Which Add Several TBs/Day
Source: Glenn Iona, EOSDIS Element Evolution
Technical Working Group January 6-7, 2005

11. Performance per Dollar Spent
Optical Networks Are Becoming the 21st Century Cyberinfrastructure Driver
Optical Fiber
(bits per second)
(Doubling time 9 Months)
Data Storage
(bits per square inch)
(Doubling time 12 Months)
Performance per Dollar Spent
Silicon Computer Chips
(Number of Transistors)
(Doubling time 18 Months) 1 2 3 4 5
Number of Years
Scientific American, January 2001

12. Internet2 Backbone is 10,000 Mbps! Throughput is < 0.5% to End User
Challenge: Average Throughput of NASA Data Products to End User is < 50 Mbps
Tested
October 2005
Internet2 Backbone is 10,000 Mbps!
Throughput is < 0.5% to End User

13. Solution: Individual 1 or 10Gbps Lightpaths -- “Lambdas on Demand”
(WDM)
“Lambdas”
Source: Steve Wallach, Chiaro Networks

14. National Lambda Rail (NLR) and TeraGrid Provides Cyberinfrastructure Backbone for U.S. Researchers
NSF’s TeraGrid Has 4 x 10Gb
Lambda Backbone
Seattle
International
Collaborators
Portland
Boise
UC-TeraGrid
UIC/NW-Starlight
Ogden/
Salt Lake City
Cleveland
Chicago
New York City
San Francisco
Denver
Pittsburgh
Washington, DC
Kansas City
Raleigh
Albuquerque
Tulsa
Los Angeles
Atlanta
San Diego
Phoenix
Dallas
Baton Rouge
Las Cruces /
El Paso
Links Two Dozen State and Regional Optical Networks
Jacksonville
Pensacola
DOE, NSF, & NASA
Using NLR
San Antonio
Houston
NLR 4 x 10Gb Lambdas Initially
Capable of 40 x 10Gb wavelengths at Buildout

15. Lambdas Give End Users Sustained ~ 10 Gbps Data Flow Rates
GSFC Scientific and Engineering Network (SEN)
Mrtg-based `Daily' Graph (5 Minute Average)
Bits per second In and Out
On Selected Interfaces
On August 5, 2005, GSFC’s Bill Fink simultaneously conducted two 15-minute-duration UDP-based 4.5-Gbps flow tests, with one flow between GSFC-UCSD and the other between GSFC-StarLight/Chicago. This filled both the NLR/WASH-STAR and DRAGON/channel49 lambdas to 90% of capacity. Flows were also tested in both directions. He measured greater than 9-Gbps aggregate in each direction and no-to-negligible packet losses.
DRAGON 10Gig DWDM XFP
5 August 2005
200 Times Faster Than Standard Internet2!
chance1 10Gig (eth1 Intel
Pro/10GbE)
5 August 2005
chance2 10Gig (eth1 Intel
Pro/10GbE)
5 August 2005
Source: Pat Gary, NASA GSFC 15

16. Global Connections Between University Research Centers at 10Gbps
Maxine Brown, Tom DeFanti, Co-Chairs i
Grid 2005
T H E G L O B A L L A M B D A I N T E G R A T E D F A C I L I T Y
September 26-30, 2005
University of California, San Diego
California Institute for Telecommunications and Information Technology
21 Countries Driving 50 Demonstrations
1 or 10Gbps to Building Sept 2005

17. NSF EarthScope and ORION
The OptIPuter Project – Creating a LambdaGrid “Web” for Gigabyte Data Objects
NSF Large Information Technology Research Proposal
Calit2 (UCSD, UCI) and UIC Lead Campuses—Larry Smarr PI
Partnering Campuses: USC, SDSU, NW, TA&M, UvA, SARA, NASA
Industrial Partners
IBM, Sun, Telcordia, Chiaro, Calient, Glimmerglass, Lucent
$13.5 Million Over Five Years
Linking Global Scale Science Projects to User’s Linux Clusters
NIH Biomedical Informatics
NSF EarthScope and ORION
Research Network

18. What is the OptIPuter?
Applications Drivers  Interactive Analysis of Large Data Sets
OptIPuter Nodes  Scalable PC Clusters with Graphics Cards
IP over Lambda Connectivity Predictable Backplane
Open Source LambdaGrid Middleware Network is Reservable
Data Retrieval and Mining  Lambda Attached Data Servers
High Defn. Vis., Collab. SW  High Performance Collaboratory
See Nov 2003 Communications of the ACM for Articles on OptIPuter Technologies

19. End User Device: Tiled Wall Driven by OptIPuter Graphics Cluster

20. Calit2 Intends to Jump Beyond Traditional Web-Accessible Databases
W E B PORTAL
(pre-filtered, queries
metadata)
Data
Backend
(DB, Files)
Request
Response
BIRN
PDB
NCBI Genbank
+ many others
Source: Phil Papadopoulos, SDSC, Calit2

21. Calit2’s Direct Access Core Architecture Will Create Next Generation Metagenomics Server
Sargasso Sea Data
Sorcerer II Expedition (GOS)
JGI Community Sequencing Project
Moore Marine Microbial Project
NASA Goddard Satellite Data
Community Microbial Metagenomics Data
Traditional
User
Dedicated
Compute Farm
(100s of CPUs)
Flat File
Server
Farm
W E B PORTAL
Request
Data-
Base
Farm
10 GigE
Fabric
Response
+ Web Services
Web
(other service)
Local
Cluster
Environment
Direct
Access
Lambda
Cnxns
TeraGrid: Cyberinfrastructure Backplane
(scheduled activities, e.g. all by all comparison)
(10000s of CPUs)
Source: Phil Papadopoulos, SDSC, Calit2

22. First Implementation of the CAMERA Complex
Compute
Database &
Storage

23. Analysis Data Sets, Data Services, Tools, and Workflows
Assemblies of Metagenomic Data
e.g, GOS, JGI CSP
Annotations
Genomic and Metagenomic Data
“All-against-all” Alignments of ORFs
Updated Periodically
Gene Clusters and Associated Data
Profiles, Multiple-Sequence Alignments,
HMMs, Phylogenies, Peptide Sequences
Data Services
‘Raw’ and Specialized Analysis Data
Rich Query Facilities
Tools and Workflows
Navigate and Sift Raw and Analysis Data
Publish Workflows and Develop New Ones
Prioritize Features via Dialogue with Community
Source: Saul Kravitz
Director of Software Engineering
J. Craig Venter Institute

24. CAMERA Timeline Release 1: Mid-2006 Release 2: Early-2007 Subsequent
Majority of GOS + Moore Microbe Genome Data
6 Gbp Has Been Assembled
Initial Versions of Core Tools
BLAST, Reference Alignment Viewer
Release 2: Early-2007
Additional Data
Additional/Improved Tools
Improved Usability
Subsequent
Move Towards Semantic DB, Direct Access
Additional Tools & Data Based on Community Feedback

25. The Bioinformatics Core of the Joint Center for Structural Genomics will be Housed in the Building
Extremely Thermostable -- Useful for Many
Industrial Processes (e.g. Chemical and Food)
173 Structures (122 from JCSG)
Determining the Protein Structures of the Thermotoga Maritima Genome
122 T.M. Structures Solved by JCSG (75 Unique In The PDB)
Direct Structural Coverage of 25% of the Expressed Soluble Proteins
Probably Represents the Highest Structural Coverage of Any Organism
Source: John Wooley, UCSD

26. Located in Calit2@UCSD Building
Providing Integrated Grid Software and Infrastructure for Multi-Scale BioModeling
National Biomedical Computation Resource
an NIH supported resource center
Located in Building
Grid and Cluster Computing Applications
Infrastructure
Rocks Grid of Clusters
APBS
Continuity
Gtomo2
TxBR
Autodock
GAMESS
QMView
Biology driven
Science has top priority
Infrastructure support
Portable solution package
Balance technology development and scientific discovery
Mix production software and new technology framework
Productive and future proof
APBS image: CCMV capsid electrostatic potential mapped on the solvent-accessible molecular surface
Zhang, D., R. Konecny, N.A. Baker, J.A. McCammon. Electrostatic Interaction between RNA and Protein Capsid in CCMV Simulated by a Coarse-grain RNA model and a Monte Carlo Approach. Biopolymers, 75(4), (2004). [link]
Abstract: Although many viruses have been crystallized and the protein capsid structures have been determined by x-ray crystallography, the nucleic acids often cannot be resolved. This is especially true for RNA viruses. The lack of information about the conformation of DNA/RNA greatly hinders our understanding of the assembly mechanism of various viruses. Here we combine a coarse-grain model and a Monte Carlo method to simulate the distribution of viral RNA inside the capsid of cowpea chlorotic mottle virus. Our results show that there is very strong interaction between the N-terminal residues of the capsid proteins, which are highly positive charged, and the viral RNA. Without these residues, the binding energy disfavors the binding of RNA by the capsid. The RNA forms a shell close to the capsid with the highest densities associated with the capsid dimers. These high-density regions are connected to each other in the shape of a continuous net of triangles. The overall icosahedral shape of the net overlaps with the capsid subunit icosahedral organization. Medium density of RNA is found under the pentamers of the capsid. These findings are consistent with experimental observations.
Figure 3. The electrostatic potential mapped on the solvent-accessible molecular surface of the capsid viewed from outside (a) and inside (b). The color bar is the same for both images.
GAMESS/QMView Lepitopterene Molecule
Autodock: Andy’s lab new paper using APBS, Autodock in J. Med. Chem
Nonhomogeneous Epicardial Strain Measurements of Anterior LV During Acute Myocardial Ischemia
Rich Clients
Web Portal
Grid Middleware
and Web Services
Workflow
APBSCommand
Middleware
PMV ADT
Vision
Telescience Portal
Continuity

27. Source: Karin Remington J. Craig Venter Institute
Metagenomics “Extreme Assembly” Requires Large Amount of Pixel Real Estate
Prochlorococcus
Microbacterium
Burkholderia
Rhodobacter
SAR-86
unknown
Source: Karin Remington
J. Craig Venter Institute

28. Source: Karin Remington J. Craig Venter Institute
Metagenomics Requires a Global View of Data and the Ability to Zoom Into Detail Interactively
Overlay of Metagenomics Data onto Sequenced Reference Genomes (This Image: Prochloroccocus marinus MED4)
Source: Karin Remington
J. Craig Venter Institute

29. The OptIPuter – Creating High Resolution Portals Over Dedicated Optical Channels to Global Science Data
300 MPixel Image!
Source: Mark Ellisman, David Lee, Jason Leigh
Green: Purkinje Cells
Red: Glial Cells
Light Blue: Nuclear DNA
Calit2 (UCSD, UCI) and UIC Lead Campuses—Larry Smarr PI
Partners: SDSC, USC, SDSU, NW, TA&M, UvA, SARA, KISTI, AIST

30. Scalable Displays Allow Both Global Content and Fine Detail
Source: Mark Ellisman, David Lee, Jason Leigh
30 MPixel SunScreen Display Driven by a 20-node Sun Opteron Visualization Cluster

31. Allows for Interactive Zooming from Cerebellum to Individual Neurons
Source: Mark Ellisman, David Lee, Jason Leigh

32. The OptIPuter Enabled Collaboratory: Remote Researchers Jointly Exploring Complex Data
Source: Mark Ellisman, NCMIR
Calit2/EVL/NCMIR Tiled Displays with HD Video
New Home of SDSC/Calit2 Synthesis Center
Source: Chaitan Baru, SDSC

33. Eliminating Distance to Unify Remote Laboratories
August 8, 2005
25 Miles
Venter Institute
SIO/UCSD
OptIPuter
Visualized
Data
NASA
Goddard
HDTV Over
Lambda

34. OptIPuter + CalREN-XD + TeraGrid = “OptiGrid”
Calit2/SDSC Proposal to Create a UC Cyberinfrastructure of “On-Ramps” to National LambdaRail Resources
UC San Francisco
UC San Diego
UC Riverside
UC Irvine
UC Davis
UC Berkeley
UC Santa Cruz
UC Santa Barbara
UC Los Angeles
UC Merced
OptIPuter + CalREN-XD + TeraGrid = “OptiGrid”
Creating a Critical Mass of End Users on a Secure LambdaGrid
Source: Fran Berman, SDSC , Larry Smarr, Calit2

35. Science Falkowski and Vargas 304 (5667): 58
Looking Back Nearly 4 Billion Years In the Evolution of Microbe Genomics
Science Falkowski and Vargas 304 (5667): 58