1. 1 Hierarchical modularity of nested bow- ties in metabolic networks Jing Zhao Jzhao@scbit.org Shanghai Jiao Tong University Shanghai Center for Bioinformation and Technology 5 August,2007 Zhao J, Yu H, Luo J, Cao Z, Li Y: Hierarchical modularity of nested bow-ties in metabolic networks. BMC Bioinformatics 2006:7:386.

2. 2 1. Background Bow-tie pattern Hierarchical organization 2.Results Topological features Relationship between topology and functionality 3. Discussion Outline

3. 3 1. Background Bow-tie pattern Hierarchical organization 2.Results Topological features Relationship between topology and functionality 3. Discussion Outline

4. 4 Csete M, Doyle J: Bow ties, metabolism and disease. Trends in Biotechnology 2004, 22:446-450. Biological viewpoint of metabolic system: bow-tie

5. 5 E.coli metabolic network Topological viewpoint of metabolic networks: bow tie

6. 6 Ma H-W, Zeng A-P: The connectivity structure, giant strong component and centrality of metabolic networks. Bioinformatics 2003, 19:1423-1430. Topological viewpoint of metabolic networks: bow tie

7. 7 Bow-tie structure in the coarse-grained graph of the E.coli metabolic network Zhao J, Yu H, Luo J, Cao Z, Li Y: Complex networks theory for analyzing metabolic networks. Chinese Science Bulletin 2006, 51(13):1529-1537. Zhao J, Tao L, Yu H, Luo J-H, Cao ZW, Li Y: Bow-tie topological features of metabolic networks and the functional significance. arXiv:q-bioMN/0611013, to appear in Chinese Science Bulletin 2007. Topological viewpoint of metabolic networks: bow tie Robust yet frangile

8. 8 1. Background Bow-tie pattern Hierarchical organization 2.Results Topological features Relationship between topology and functionality 3. Discussion Outline

9. 9 Life’s complex Pyramid Oltvai, Z.N., Barabási, A.-L., Life’s Complexity Pyramid, SCIENCE, 2002, 298:763- 764. Biological viewpoint of biological systems: hierarchical organization

10. 10 Topological viewpoint of metabolic networks: hierarchical modularity Ravasz E, Somera A L, Mongru D A, Oltvai Z N, Barabasi A L, Hierarchical organization of modularity in metabolic networks, Science,2002,297: 1551-1556

11. 11 Functional modules: protein complexes, signalling/metabolic pathways and transcriptional clusters Network topological modules Different viewpoint of modules Har Hartwell LH, Hopfield JJ, Leibler S, Murray AW: From molecular to modular cell biology. Nature 1999, 402:C47-C52. Newman MEJ, Girvan M: Finding and evaluating community structure in networks. Physical Review E 2004, 69:026113. Protocols: the “rules” by which modules interact.

12. 12 1. Background Bow-tie pattern Hierarchical organization 2.Results Topological features Relationship between topology and functionality 3. Discussion Outline

13. 13 Topological feature: bow-tie modules Decomposition of the E.coli metabolic network

14. 14 The connections among the GSC parts of the twelve bow-tie like modules. Topological feature: hierarchically nested bow-tie organization

15. 15 Topological feature: Compared with randomized counterparts Comparison of the Core of E.coli network with that of a randomized network.

16. 16 1. Background Bow-tie pattern Hierarchical organization 2.Results Topological features Relationship between topology and functionality 3. Discussion Outline

17. 17 Cartographic representation of the metabolic network for E.coli.. Topology vs. functionality: functional clustering of bow-tie modules

18. 18 Case 1: most modules are dominated by one major category of metabolisms Topology vs. functionality: Are bow-tie modules also functional modules?

19. 19 Topology vs. functionality: Are bow-tie modules also functional modules? Case 2 : Some modules are mixtures of pieces of several conventional biochemical pathways.

20. 20 Topology vs. functionality: Are bow-tie modules also functional modules? Case 3 : A standard textbook pathway can break into several modules.

21. 21 Topology vs. functionality: e Bow-tie topology of functional modules 1.Chemical modules: 75 organisms carbohydrate metabolism: bow-tie lipid metabolism: not bow-tie amino acid metabolism: not bow-tie 2. Spatial modules: yeast cytosol: bow-tie mitochondrion: bow-tie peroxisome: not bow-tie

22. 22 1. Background Bow-tie pattern Hierarchical organization 2.Results Topological features Relationship between topology and functionality 3. Discussion Outline

23. 23 Significance of nested bow-tie organization Bow-tie modules may act as another kind of building block of metabolic networks Nested bow-tie organization contributes to system robustness “Thick bow-tie” vs “Thin bow-tie”

24. 24 Thanks!