This document discusses genome annotation and modeling from genomes to pathways and simulations. It begins by outlining the genome annotation process from identifying open reading frames (ORFs) to functional annotation. It then discusses qualitative and quantitative modeling in systems biology, noting that qualitative modeling can be highly automated but quantitative modeling is more difficult. The document introduces the GEM System for building genome-scale metabolic models and shows example coverage for several species. It also compares qualitative modeling results before and after improving the GEM System and annotation. Finally, it discusses current challenges with quantitative modeling databases and introduces the ISM database as an alternative that aims to address limitations of other options through curation and additional features.

1. 1
From Genome
to Pathways and Simulation
G

3. 1000+

4. genome
ORFs
proteins
genome annotation

5. genome
ORFs
proteins
ORF identification
Functional Annotation
genome annotation

6. genome
ORFs
proteins
Glimmer/GeneMark
BLAST/InterProScan
genome annotation

7. genome
ORFs
proteins
96-99% Automation
50-70% Automation
genome annotation

8. Systems Biology

9. Systems Biology
target
qualitative model
quantitative model

10. Qualitative Modeling
Quantitative Modeling
Systems Biology
target
qualitative model
quantitative model

11. Systems Biology
target
qualitative model
quantitative model

12. 0% Automation
Systems Biology
target
qualitative model
quantitative model

13. GEM System

14. GEM System
from genome to simulation

15. GEM System
from to Automation

17. species genes reactions metabolites KEGG coverage
B. subtilis 4106 2009 1465 79.37%
E.coli K12 4289 2282 1568
91.21%
H. influenzae 1709 1557 1166 89.78%
M. genitalium 480 548 469
94.32%
P. aeruginosa 5566 1877 1365 82.05%
Qualitative Modeling

18. Incubation (min)
Concentration(μM)
A
B
A: Results of time-course measure of in vitro glycolysis experiment
B: Results of simulation of in silico glycolysis model
Quantitative Modeling

19. Qualitative Modeling (E.coli)
9%
91%
KEGG

20. Qualitative Modeling (E.coli)
9%
91%
52%
48%
False Positive? KEGG

21. 9%
91%
52%
48%
False Positive? KEGG
Qualitative Modeling (E.coli)
Before

22. 9%
91%
52%
48%
False Positive? KEGG
Qualitative Modeling (E.coli)
Before
GEM System
rev. 2

23. 100% 100%
5%
95%
95%
9%
91%
52%
48%
False Positive? KEGG
Qualitative Modeling (E.coli)
Before
7%2%
22%
69%
KEGG
SWISSPROT
Palsson
After

24. Qualitative Modeling
Systems Biology
target
qualitative model
quantitative model

25. Qualitative Modeling
Systems Biology
target
qualitative model
quantitative model

26. Qualitative Modeling
93-100% Automation
Systems Biology
target
qualitative model
quantitative model

28. Demo

33. Keyword is “Database”

34. One more thing...

35. Qualitative Modeling
93-100% Automation
Systems Biology
target
qualitative model
quantitative model

36. Okay, but what about
QUANTITATIVE Modeling?

37. genome
ORFs
proteins
ORF identification
Functional Annotation
Glimmer/GeneMark
genome annotation
BLAST

38. Pavesy JWS Online
SBML Repository ECDN

40. Few Models
Available
Torturing
Interface
No Search
No Help
For Modeling

41. Torturing
Interface

42. in silico model DB

43. ism

44. ism
Model Database
• 700+ Kinetic equations

45. ism
Model Database
• 700+ Kinetic equations
• 1300+ Kinetic parameters

46. ism
Model Database
• 700+ Kinetic equations
• 1300+ Kinetic parameters
• Smart Search

47. ism
Model Database
• 700+ Kinetic equations
• 1300+ Kinetic parameters
• Smart Search
• Human curated

48. ism
Model Database
• 700+ Kinetic equations
• 1300+ Kinetic parameters
• Smart Search
• Human curated
• Detailed annotation

49. ism
Model Database
• 700+ Kinetic equations
• 1300+ Kinetic parameters
• Smart Search
• Human curated
• Detailed annotation
• CAS/EC Number ID

50. ism
Model Database
• 700+ Kinetic equations
• 1300+ Kinetic parameters
• Smart Search
• Human curated
• Detailed annotation
• CAS/EC Number ID
• Online simulation

51. ism
Model Database
• 700+ Kinetic equations
• 1300+ Kinetic parameters
• Smart Search
• Human curated
• Detailed annotation
• CAS/EC Number ID
• Online simulation
• Pathway graphics

52. ism
Model Database
• 700+ Kinetic equations
• 1300+ Kinetic parameters
• Smart Search
• Human curated
• Detailed annotation
• CAS/EC Number ID
• Online simulation
• Pathway graphics
• SBML ready

53. Demo

60. Modeling

65. Interface

68. Editor

73. • SOAP API for direct sync with GEM System

74. • SOAP API for direct sync with GEM System
• 200+ Models