1. An Integrated Computational Framework for Systems Biology Ram Samudrala University of Washington How does the genome of an organism specify its behaviour and characteristics?

2. Proteome – all proteins of a particular system

3. Modelling proteomes – understand the structure of individual proteins

4. Modelling proteomes – understand their individual functions

5. Modelling proteomes – understand their expression

6. Modelling proteomes – understand their interactions

7. Integrated structural and functional annotation of proteomes structure based methods microenvironment analysis zinc binding site? structure comparison homology function? sequence based methods sequence comparison motif searches phylogenetic profiles domain fusion analyses + * * * * Bioverse * * assign function to entire protein space experimental data single molecule + genomic/proteomic + EXPRESSION + INTERACTION }

8. Bioverse – explore relationships among molecules and systems Jason McDermott/Michal Guerquin/Zach Frazier http://bioverse.compbio.washington.edu

9. Bioverse – explore relationships among molecules and systems Jason McDermott/Michal Guerquin/Zach Frazier http://bioverse.compbio.washington.edu

10. Bioverse – explore relationships among molecules and systems Jason McDermott/Michal Guerquin/Zach Frazier http://bioverse.compbio.washington.edu

11. Bioverse – explore relationships among molecules and systems Jason McDermott/Michal Guerquin/Zach Frazier http://bioverse.compbio.washington.edu

12. Bioverse – prediction of protein interaction networks Jason McDermott Interacting protein database protein α protein β experimentally determined interaction Target proteome protein A 85% predicted interaction protein B 90% Assign confidence based on similarity and strength of interaction

13. Bioverse – E. coli predicted protein interaction network Jason McDermott

14. Bioverse – M. tuberculosis predicted protein interaction network Jason McDermott

15. Bioverse – C. elegans predicted protein interaction network Jason McDermott

16. Bioverse – H. sapiens predicted protein interaction network Jason McDermott

17. Bioverse – network-based annotation for C. elegans Jason McDermott

18. Articulation point proteins Bioverse – identifying key proteins on the anthrax predicted network

19. Jason McDermott Bioverse – identification of virulence factors

20. Bioverse - Integrator Aaron Chang

21. Take home message Prediction of protein structure, function, and networks may be used to model whole genomes to understand organismal function and evolution

22. Acknowledgements Aaron Chang Chuck Mader David Nickle Ekachai Jenwitheesuk Gong Cheng Jason McDermott Kai Wang Ling-Hong Hung Mike Inouye Michal Guerquin Stewart Moughon Shing-Chung Ngan Tianyun Liu Zach Frazier National Institutes of Health National Science Foundation Searle Scholars Program (Kinship Foundation) UW Advanced Technology Initiative in Infectious Diseases http://bioverse.compbio.washington.edu http://protinfo.compbio.washington.edu