Systems BiologyBiological Sequence Analysis 27803

27803::Systems Biology2 CBS, Department of Systems Biology

Schedule for the morning09:05 – 09:20 Survey09:20 – 10:00 Introduction and Motivation10:00 – 10:20 Coffee Break10:20 – 10:50 Interaction networks: data and properties10:50 – 11:10 Discussion: Pluses/minuses of HTP interaction

data sets11:10 – 12:00 Exercise

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Motivation for Systems Biology

27803::Systems Biology5 CBS, Department of Systems Biology

27803::Systems Biology6 CBS, Department of Systems Biology

27803::Systems Biology7 CBS, Department of Systems Biology

Increasing Interest in Bioinformatics & Systems Biology

27803::Systems Biology8 CBS, Department of Systems Biology

Systems biology and emerging properties

27803::Systems Biology9 CBS, Department of Systems Biology

Transcriptional regulation of the Cell Cycle

Simon et al. Cell 2001

27803::Systems Biology10 CBS, Department of Systems Biology

27803::Systems Biology11 CBS, Department of Systems BiologyTyson JJ, Novak B, J. Theor. Biol. 2001

27803::Systems Biology12 CBS, Department of Systems Biology

Boehringer Mannheim metabolic map

27803::Systems Biology13 CBS, Department of Systems Biology

Mathematical abstraction of biochemistry

27803::Systems Biology14 CBS, Department of Systems Biology

Metabolic models

27803::Systems Biology15 CBS, 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.

27803::Systems Biology16 CBS, 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.

27803::Systems Biology17 CBS, 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).

27803::Systems Biology18 CBS, Department of Systems Biology

From model to experiment and back again