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Systems Biology Biological Sequence Analysis 27803.

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1 Systems Biology Biological Sequence Analysis 27803

2 27803::Systems Biology2CBS, 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

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

4 Motivation for Systems Biology

5 27803::Systems Biology5CBS, Department of Systems Biology

6 27803::Systems Biology6CBS, Department of Systems Biology

7 27803::Systems Biology7CBS, Department of Systems Biology Increasing Interest in Bioinformatics & Systems Biology

8 27803::Systems Biology8CBS, Department of Systems Biology Systems biology and emerging properties

9 27803::Systems Biology9CBS, Department of Systems Biology Transcriptional regulation of the Cell Cycle Simon et al. Cell 2001

10 27803::Systems Biology10CBS, Department of Systems Biology

11 27803::Systems Biology11CBS, Department of Systems Biology Tyson JJ, Novak B, J. Theor. Biol. 2001

12 27803::Systems Biology12CBS, Department of Systems Biology Boehringer Mannheim metabolic map

13 27803::Systems Biology13CBS, Department of Systems Biology Mathematical abstraction of biochemistry

14 27803::Systems Biology14CBS, Department of Systems Biology Metabolic models

15 27803::Systems Biology15CBS, Department of Systems Biology “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.

16 27803::Systems Biology16CBS, 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.

17 27803::Systems Biology17CBS, 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).

18 27803::Systems Biology18CBS, Department of Systems Biology From model to experiment and back again

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