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  • Global regulators: CRP (glucose starvation) and RpoS (general stress in bacteria) ; q: do you think any striking feature exists in this network? Does it look homogeneous?
  • The ratio P(K0,K1)/Pr(K0,K1), whereP(K0,K1) is the probability that a pair of proteins with total numbers of interaction partners given by K0,K1 correspondingly, directly interact with each other in the full set of (2), whilePr(K0,K1) is the same probability in a randomized version of the same network. (B) The same as in (A) but for a protein with the in-degree Kin to be regulated by that with the out-degree Kout in the transcription regulatory network (3). 
  • Cak1p is a cyclin-dependent kinase-activating kinase involved in two key signaling-transduction pathways: cell cycle and sporulation.
  • GLEaM is a discrete stochastic epidemic computational model based on a meta-population approach in which the world is defined in geographical census areas connected in a network of interactions by human travel fluxes corresponding to transportation infrastructures and mobility patterns. The GLEaM 2.0 simulation engine includes a multiscale mobility model integrating different layer of transportation networks ranging from the long range airline connections to the short range daily commuting pattern.


  • 1. Graph properties of biological networks Modeling of Biological Systems UCSF, May 8 2009 natali.gulbahce@gmail.com
  • 2. Chemotaxis via differential equations
  • 3. Cell cycle via Boolean modeling
  • 4. Large-scale cellular networks • Transcriptional factor binding networks • Protein-protein interaction networks • Metabolic networks • Protein phosphorylation networks • Genetic interaction networks
  • 5. Numbers Zhu et al. Gen. & Dev. (2007)
  • 6. Transcription factor binding networks Sea urchin: Davidson et al. 2002 Large scale identification of TF-binding sites using ChIP-chip or DNA sequencing Yeast and mammalian cells: Horak and Snyder 2005; Kim et al.; Wei et al 2006.
  • 7. Human Interactome Protein Y2H (Rual et al.) Literature Yeast: Yu et al. 2008; Krogan et al. Human: Rual et al 2005; Stelzl et al 2005. 2006; Gavin et al. 2006; Ito et al Drosophila: Giot et al. 2003. 2001; Uetz et al 2000. C. elegans: Li et al 2004.
  • 8. E. Coli Metabolic Network Nodes: metabolites Edges: reactions Kegg, Wit, Biocyc, Bigg (UCSD)
  • 9. Yeast phosphorylome Kinase Substrate Yeast: Ptacek et al. 2005 H. Sapiens: Linding et al. 2007 Phospho.elm
  • 10. Yeast genetic interaction network Tong et al. 2001; Roguev et al. 2007.
  • 11. Why study these large scale networks?
  • 12. In this class • Network measures: degree, clustering, assortativity, betweenness centrality, motifs, modularity. • Networks: random, small world, scale-free. • Simple models, essentiality, topological robustness.
  • 13. Human interactome follows a power-law HUBS Distribution is the same without the bias introduced by well- studied proteins.
  • 14. Yeast ; Zhu et al. Gen. & Dev. (2007)
  • 15. Assortativity • A preference for a network's nodes to attach to others that are similar or different in degree. Maslov and Sneppen, 2002. P(K0,K1)/PR(K0,K1) Yeast interactome Yeast transcriptome
  • 16. Non-Hub Bottleneck in Yeast Interactome Cak1p is a cyclin- dependent kinase- activating kinase involved in two key signaling pathways.
  • 17. Hubs, bottlenecks: which are more essential? NH-NB: Non-hub, non-bottleneck; H-NB: Hub, non-bottleneck; B-NH: Bottleneck, non-hub; BH: Bottleneck, hub. Yu et al. 2007.
  • 18. Watts and Strogatz, Nature (1998).
  • 19. Milo et al Science 2002
  • 20. How to randomize a network Network randomization is used to determine the statistical significance of a quantity, or how happy you should be about a research result. • Shuffle everything. • Conserve the degree. • Conserve the connectedness of the network.
  • 21. Cfinder www.cfinder.org Palla et al. Nature (2005).
  • 22. Error and attack tolerance d f f Albert et al. Nature (2000).
  • 23. Date hubs vs. party hubs Non-hubs Hubs Hubs (random)
  • 24. Date hubs vs. party hubs Date hubs organize the proteome, connecting biological processes—or modules—to each other, whereas party hubs function inside modules.
  • 25. May 17 Swine Flu prediction gleamviz.org
  • 26. Further References • Barabasi and Oltvai, “Network biology: understanding the cell’s functional organization,” Nature Reviews Genetics, 2004. • Zhu, Gerstein and Snyder, “Getting connected: analysis and principles of biological networks,” Genes and Development, 2007.