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Systems Biology

Systems Biology. Biological Sequence Analysis 27803. Schedule for the morning. 09:05 – 09:20 Survey 09:20 – 10:00 Introduction and Motivation 10:00 – 10:20 Coffee Break 10:20 – 10:50 Interaction networks: data and properties

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Systems Biology

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  1. Systems Biology Biological Sequence Analysis 27803

  2. Schedule for the morning 09:05 – 09:20 Survey 09:20 – 10:00 Introduction and Motivation 10:00 – 10:20 Coffee Break 10:20 – 10:50 Interaction networks: data and properties 10:50 – 11:10 Discussion: Pluses/minuses of HTP interaction data sets 11:10 – 12:00 Exercise

  3. Survey Please follow the link from the course page..

  4. Motivation for Systems Biology

  5. Increasing Interest in Bioinformatics & Systems Biology

  6. Systems biology and emerging properties

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

  8. Tyson JJ, Novak B, J. Theor. Biol. 2001

  9. Boehringer Mannheim metabolic map

  10. Mathematical abstraction of biochemistry

  11. Metabolic models

  12. “Genome scale” metabolic models • 2342 reactions (including 2183 metabolic reactions) • 2657 chemical species • 1494 metabolites • 1163 proteins or complexes (as of April 2010) Herrgård, Swainston et al. (2008) "A consensus yeast metabolic reconstruction obtained from a community approach to systems biology" Nature Biotechnol. 26, 1155-1160. Forster et al. Genome Research 2003.

  13. One framework for Systems Biology (part 1) • The components.Discoverall 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?).  • 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.

  14. One framework for Systems Biology (part 2) • 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. • 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).

  15. From model to experiment and back again

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