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.

17. Human interactome follows a power-law
HUBS
Distribution is the same without the bias introduced by well-
studied proteins.

19. Yeast ; Zhu et al. Gen. & Dev. (2007)

21. 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

24. Non-Hub Bottleneck in Yeast Interactome
Cak1p is a cyclin-
dependent kinase-
activating kinase
involved in two key
signaling pathways.

25. 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.

27. Watts and Strogatz, Nature (1998).

28. Milo et al Science 2002

29. 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.

31. Cfinder
www.cfinder.org
Palla et al. Nature (2005).

41. Error and attack tolerance
d
f
f
Albert et al. Nature (2000).

42. Date hubs vs. party hubs
Non-hubs
Hubs
Hubs (random)

43. Date hubs vs. party hubs
Date hubs organize the proteome, connecting
biological processes—or modules—to each
other, whereas party hubs function inside modules.

45. May 17 Swine Flu prediction
gleamviz.org

46. 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.