1. Systems Biology Biological Sequence Analysis 27803

2. 27803::Systems Biology2CBS, Department of Systems Biology Meet Your Instructor Christopher Workman –CBS-Regulatory Genomic group leader –CBS-Integrative Systems Biology group (interloper) BA Biochemistry and Molecular Biology (University of Colorado) MS Computer Science (University of Colorado) PhD Bioinformatics (DTU)

3. 27803::Systems Biology3CBS, Department of Systems Biology Schedule for the morning 09:05 – 09:20Survey 09:20 – 10:00Introduction and Motivation 10:00 – 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 Please follow the link from the course page..

5. 27803::Systems Biology5CBS, Department of Systems Biology What are you most interested in learning about today? (your answers here…)

6. Motivation for Systems Biology

7. 27803::Systems Biology7CBS, Department of Systems Biology

8. 27803::Systems Biology8CBS, Department of Systems Biology

9. 27803::Systems Biology9CBS, Department of Systems Biology Increasing Interest in Systems Biology. Why? Human genome completed PubMed abstracts

10. 27803::Systems Biology10CBS, Department of Systems Biology Systems biology and emerging properties

11. 27803::Systems Biology11CBS, Department of Systems Biology Transcriptional regulation of the Cell Cycle Simon et al. Cell 2001

12. 27803::Systems Biology12CBS, Department of Systems Biology

13. 27803::Systems Biology13CBS, Department of Systems Biology Tyson JJ, Novak B, J. Theor. Biol. 2001

14. 27803::Systems Biology14CBS, Department of Systems Biology Boehringer Mannheim metabolic map

15. 27803::Systems Biology15CBS, Department of Systems Biology Mathematical abstraction of biochemistry

16. 27803::Systems Biology16CBS, Department of Systems Biology Metabolic models

17. 27803::Systems Biology17CBS, Department of Systems Biology “Genome scale” metabolic models Genes708 Metabolites584 –Cytosolic559 –Mitochondrial164 –Extracellular121 Reactions1175 –Cytosolic702 –Mitochondrial124 –Exchange fluxes349 Forster et al. Genome Research 2003.

18. 27803::Systems Biology18CBS, Department of Systems Biology One framework for Systems Biology (part 1) 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.

19. 27803::Systems Biology19CBS, Department of Systems Biology One framework for Systems Biology (part 2) 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).

20. 27803::Systems Biology20CBS, Department of Systems Biology From model to experiment and back again

21. 27803::Systems Biology21CBS, Department of Systems Biology Systems biology paradigm Aebersold R, Mann M, Nature, 2003.