1. Systems Biology Biological Sequence Analysis 27803

2. Meet Your Instructor Christopher Workman –CBS-DTU –Regulatory Genomic –Integrative Systems Biology

3. Schedule for the morning 09:00 – 09:25Pre-module quiz 09:25 – 09:50Introduction and Motivation 09:50 – 10:20Coffee Break 10:20 – 10:50Interaction networks: data and properties 10:50 – 11:10Discussion: Pluses/minuses of HTP interaction data sets 11:10 – 12:00 Exercise

4. Survey/Quiz

5. What reasons do you think makes Systems Biology a “hot topic”? (your answers here…)

6. What are you most interested in learning about today? (your answers here…)

7. Motivation for Systems Biology

8. Interest in Systems Biology? Human genome completed PubMed abstracts

9. Systems biology and emerging properties

10. Transcriptional regulation of the Cell Cycle Simon et al. Cell 2001

11. Boehringer Mannheim metabolic map

12. Mathematical abstraction of biochemistry

13. Metabolic models

14. “Genome scale” metabolic models Genes708 Metabolites584 –Cytosolic559 –Mitochondrial164 –Extracellular121 Reactions1175 –Cytosolic702 –Mitochondrial124 –Exchange fluxes349 Forster et al. Genome Research 2003.

15. One framework for Systems Biology 1.The components. Discover all of the genes in the genome and the subset of genes, proteins, and other small molecules constituting the pathway of interest. If possible, define an initial model of the molecular interactions governing pathway function (how?). 2.Pathway perturbation. Perturb each pathway component through a series of genetic or environmental manipulations. Detect and quantify the corresponding global cellular response to each perturbation.

16. One framework for Systems Biology 3.Model Reconciliation. Integrate the observed mRNA and protein responses with the current, pathway-specific model and with the global network of protein-protein, protein-DNA, and other known physical interactions. 4.Model verification/expansion. Formulate new hypotheses to explain observations not predicted by the model. Design additional perturbation experiments to test these and iteratively repeat steps (2), (3), and (4).

17. From model to experiment and back again

18. Systems biology paradigm Aebersold R, Mann M, Nature, 2003.