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