Systems Biology
Biological Sequence Analysis 27803
Schedule for the morning
09:05
09:20
10:00
10:20
10:50
Survey
Introduction and Motivation
Coffee Break
Interaction networks: data and properties
Discussion: Pluses/minuses of HTP interaction
data sets
11:10 – 12:00 Exercise
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10:00
10:20
10:50
11:10
CBS, Department of Systems Biology
27803::Systems Biology
Survey
Please follow the link from the course page..
Motivation for
Systems Biology
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CBS, Department of Systems Biology
27803::Systems Biology
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CBS, Department of Systems Biology
27803::Systems Biology
Increasing Interest in Bioinformatics &
Systems Biology
15000
PubMed
Term
Nobel Prize for Cell Cycle
Bioinformatics
Systems Biology
Cell Cycle
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Publications
10000
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Human genome completed
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Yeast genome completed
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1995
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2005
2000
2010
Year
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CBS, Department of Systems Biology
27803::Systems Biology
Systems biology and emerging properties
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CBS, Department of Systems Biology
27803::Systems Biology
Transcriptional regulation of the Cell Cycle
Simon et al. Cell 2001
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CBS, Department of Systems Biology
27803::Systems Biology
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CBS, Department of Systems Biology
27803::Systems Biology
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CBS, Department of Systems Biology
Tyson JJ, Novak B, J. Theor. Biol. 2001
27803::Systems Biology
Boehringer Mannheim metabolic map
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CBS, Department of Systems Biology
27803::Systems Biology
Mathematical abstraction of biochemistry
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CBS, Department of Systems Biology
27803::Systems Biology
Metabolic models
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CBS, Department of Systems Biology
27803::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.
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CBS, Department of Systems Biology
27803::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.
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CBS, Department of Systems Biology
27803::Systems Biology
One framework for Systems Biology (part 2)
3.
Model Reconciliation. Integrate the observed mRNA
and protein responses with the current, pathwayspecific model and with the global network of proteinprotein, 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).
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CBS, Department of Systems Biology
27803::Systems Biology
From model to experiment and back again
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CBS, Department of Systems Biology
27803::Systems Biology