Cyber Metagenomics; Challenge to See The Unseen Majority in The Ocean Kayo Arima California Institute for Telecommunications and Information Technology (Calit2)-University of California, San Diego Division

Science Falkowski and Vargas 304 (5667): 58 Looking Back Nearly 4 Billion Years In the Evolution of Microbe Genomics Eukaryote has the nuclei . Prokaryotes has genes but no nuclear membrane. Science Falkowski and Vargas 304 (5667): 58

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

Two completely different approach to get microbial genomic information Microbial whole genomics Metagenomics Environmental sample Culture (grow) in lab Isolate the colony Culture the isolated colony DNA extraction Enz. digestion Shotgun sequencing Gene assembly Environmental sample DNA extraction Enz. digestion Shotgun sequencing Scaffold assembly                  Source: Karin Remington J. Craig Venter Institute

Down Side of Metagenomics Often fragmentary Often highly divergent Rarely any known activity No chromosomal placement No organism of origin Ab initio ORF predictions Huge data

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 www.ncbi.nlm.nih.gov/Genbank www.rcsb.org/pdb/holdings.html Total Data < 1TB

First Genome 1995 6 Genomes/ Year 2000 Full Genome Sequencing is Exploding: Most Sequenced Genomes are Bacterial First Genome 1995 6 Genomes/ Year 2000 Ongoing Genomes Completed Genomes 90 Metagenomes Total 422 Total 1665 www.genomesonline.org

Marine Metagenomics Microbes account for more than 90% of ocean biomass, mediate all biochemical cycles in the oceans and are responsible for 98% of primary production in the sea. Metagenomics is a breakthrough sequencing approach to examine the open-space microbial species without the need for isolation and lab cultivation of individual species.

PI Larry Smarr Paul Gilna Ex. Dir. PI Larry Smarr

Marine Genome Sequencing Project Measuring the Genetic Diversity of Ocean Microbes Sorcerer II Data from this area has already reach to 10% of GenBank. The Entire Data Will Double Number of Proteins in Embank!

Sample Metadata from GOS Site Metadata Location (lat/long, water depth) Site characterization (finite list of types plus “other”) Site description (free text) Country Sampling Metadata Sample collection date/time Sampling depth Conditions at time of sampling (e.g., stormy, surface temperature) Sample physical/chemical measurements (T (oC), S (ppt), chl a (mg m-3), etc) “author” Experimental Parameters Filter size Insert size

Flat File Server Farm W E B PORTAL Traditional User Response Request Dedicated Compute Farm (1000 CPUs) TeraGrid: Cyberinfrastructure Backplane (scheduled activities, e.g. all by all comparison) (10000s of CPUs) Data- Base 10 GigE Fabric Calit2’s Direct Access Core Architecture Will Create Next Generation Metagenomics Server Source: Phil Papadopoulos, SDSC, Calit2 + Web Services Sargasso Sea Data Sorcerer II Expedition (GOS) JGI Community Sequencing Project Moore Marine Microbial Project NASA Goddard Satellite Data Community Microbial Metagenomics Data Web (other service) Local Cluster Environment Direct Access Lambda Cnxns

Who is there? Marine Metagenomics Metabolic pathway discovery Drug discovery Microbial genetic survey Environmental survey Symbiosis Who is there? Evolution study Endosymbiosis Organism discovery Microbial genomic survey Bioenergy discovery Biogeochemistry mapping Marine conservation