1. Design principle of biological networks—network motif

3. Definition of motifs Motifs are those subgraphs that occur significantly more often in the real network than in randomized networks.

4. Network motifs Original network Random version of original network

5. Criteria for network motif

6. Motifs in genetic network of yeast

7. Motifs in genetic network of E. coli

8. Enumeration methods to identify motifs Generating an ensemble of random networks Counting subgraphs in real network and random network

10. Subgraph concentration

11. Random sampling of n node subgraphs Pick a random edge from the network and expand the subgraph iteratively by picking random neighboring edges until the subgraph reaches n nodes.

12. Sampling algorithm

13. P: probability of sampling a specific subgraph Define a score S i for each subgraph of type i, and set to S i zero initially. S i = S i +1/P until S T samplings are finished. Assume L types of subgraphs were sampled.

15. Compare between sampling and enumeration

16. Runtime complexity analysis

17. Conservation of network motif constituents Homo SapiensMus musculus Drosophila melanogaster C. elegans Arabidopsis thaliana Saccharomyces cerevisiae Four nodes motif Orthologs

18. Inparanoid: Eukaryotic Ortholog Groups

19. Evolution conservation of motif

22. Network motif software

24. Homework Download the mfinder motif detection software from Uri Alon’s web page, http://www.weizmann.ac.il/mcb/UriAlon Read the manual and make yourself being familiar with this software. Use this software to find the motifs for the E. coli gene regulatory network. The interaction file can be downloaded from Uri Alon’s homepage. http://www.weizmann.ac.il/mcb/UriAlon

25. References Uri Alon, An Introduction to Systems Biology: Design Principles of Biological Circuits