Microbial Genomics

1. Microbial Genomics Nikos Kyrpides Genome Biology Program (GBP) DOE Joint Genome institute

2. 4319 Genome Projects http://www.genomesonline.org/

3. UNDERSTANDING vs INFORMATION Do we really need more sequencing?

4. Genome projects 2000 Genome projects 2008 11% 71 bacterial genomes 2289 bacterial genomes Not much has changed…

5. Many gaps Poor sequence coverage mainly due to lack of isolates, but many gaps have unsequenced representatives

6. 99% of microorganisms are not cultured with present methods. Culturable Unculturable the Uncultured majority

7. Major Transitions in the2nd Decade in Genomics Transition 1 Genomes  Metagenomes 

8. Genomics  Metagenomics Sargasso sea Acid Mine Drainage Tyson et al. Nature. 2004 Mar 4;428(6978):37-43. Venter et al. Science. 2004 Apr 2;304(5667):66-74.

9. Species Complexity Binning ? Soil Sargasso Sea Termite Hindgut Human Gut Acid Mine Drainage Species complexity 1 10 100 1000 10000

10. Major Transitions in the2nd Decade in Genomics Transition 1 Genomes  Metagenomes Transition 2 Individual Genome Projects  Large Scale Projects

11. Reference Genomes Individual Genome Projects  Large Scale Projects

12. GEBA 2007 255 Genome Projects ~ 60 Finished Coordination Group Jonathan Eisen Phil Hugenholt Hans-Peter Klenk Nikos Kyrpides Hans-Peter Klenk

13. Novel Cellulolytic enzymes Non-reducing end Reducing end cellulose Endoglucanases Processive exoglucanase (reducing end) Processive exoglucanase (non-reducing end) Processive endoglucanase cellotetraose cellopentaose cellobiose b-glucosidase Glc Glc * Only 1 other enzyme of this family is known Complete cellulase systems of different compositions found in 4 genomes: • Xylanimonas cellulosilytica ( known cellulose degrader, proteomics data in multiple conditions to come) • Cellulomonas flavigena (known cellulose degrader, proteomics data in multiple conditions to come) • Catenulispora acidiphila (not known to degrade cellulose, collaborators are doing experiments) • Streptosporangium roseum (not known to degrade cellulose)

14. Major Transitions in the2nd Decade in Genomics Transition 1 Genomes  Metagenomes Transition 2 Individual Genome Projects  Large Scale Projects Transition 3 Populations  Single Cells

15. Isolating Single Cells

16. Single Cell Lysis and Amplification

17. What about the avalanche

18. GREAT CHALLENGES P. Chain et al. Science, 2009

19. Human Gut: ~ 1000 Microbes 3 Million Genes GREAT CHALLENGES Metagenomics – Environmental Genomics

20. ENGINEERING CONCEPTUAL SOLUTIONS Where do we go from here

21. GREAT CHALLENGES DATA PROCESSING DATA COMPARISON DATA BROWSING • Need better ways • to represent multiple genomes • to store and present data • to compute similarities • to represent an organism Transition 4 1000s Genomes  Pangenomes

22. 10 Prochlorococcus marinus Pangenome 17 Listeria monocytogenes Pangenome Staphylococcus aureus Pangenome 15

23. 14765 2733 = 5.4 10434 5820 = 1.8

24. PARADIGM SHIFT 1960-1990 1990-2010 16S RNA 2010-2020 Genomes Pangenomes

25. Genomic Standards Consortium Dawn Field Metadata • Habitat • DNA Source • Isolation • Phenotype

26. Why MetaData ?

27. GSC-8 | DOE-JGI | Sept 9-11, 2009 http://gensc.org/ Genomic Standards Consortium

28. Type Strains: 27% Type Strains: 20% Culture Collections 35% 53% http://www.genomesonline.org/

29. http://www.genomesonline.org/

30. http://standardsingenomics.org/ July 20, 2009 SIGS is an open-access, standards-supportive publication that seeks to rapidly disseminates concise genome and metagenome reports in compliance with MIGS/MIMS standards. SIGS also seeks to present detailed standard operating procedures, meeting reports, reviews and commentaries, data policies, white papers and other gray literature that is relevant to genome sciences, but absent from the scholarly literature. George Garrity

31. Genomic Standards Consortium Data Processing • Sequencing • Finishing • Assembly • Gene Finding Metadata • Habitat • DNA Source • Isolation • Phenotype Patrick Chain

32. Conclusions • Microbial diversity remains largely uncovered • The vast majority of currently ongoing genome projects do not cover novel grounds • To understand an organism we need to sequence a reasonable number of closely related strains • We need Standards

33. Global Genome Census for Microbes

34. INTERNATIONAL MICROBIAL CENSUS

35. CENSUS TARGETS • Sequence at least one representative from every characterized microbial Genus • Sequence at least one representative from every characterized microbial species • Sequence sufficient number of strains to characterize each species and generate the species pangenome • Understand the effects of geographic distribution on species dynamics

36. KEY PARTNERS • GSC • CULTURE COLLECTION CENTERS • DSMZ [Hans-Peter Klenk] • REPRESENTATIVES FROM GRAND CHALLENGE PROJECTS • GEBA [Phil Hugenholtz, Jonathan Eisen] • TERRAGENOME [Janet Jansson] • HMP [George Weinstock, Karen Nelson] • KEY CORE PARTICIPANTS • Large Sequencing Centers • Country members

37. Building a roadmap for a scaleable and sustainable computing MetaInfrastructure for the metagenomics community GSC Biocomputing Consortium Folker Meyer innovation through collaboration

39. MEGA Microbial Environmental Genomics Administration