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Source Bohringer-Mannheim
The History of Biological Networks
Structures
Strings, Physical Structures,….
Networks: Objects with relationships or discrete transformation
Pattern and Form
Dynamics
The Fundamental Problem:
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To use observations:
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expression levels
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enzyme concentrations
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metabolite concentrations
…….
To infer underlying network, its structure, dynamics, evolution,
function and interactions
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The Origins of Metabolic Research
1840s - the first edge!! Justus von Liebig (1803-73) in
the 1840s studied the conversion of malic acid to
fumaric acid.
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1860s - Pasteur studies fermentation
fermentation could occur in cell free extracts
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Emil Hermann Fischer
1897 - Edvard Buchner showed that
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1852-1919 NP1902
1890s - Fischer structure and conversion of sugars
1910s-20s - Michaelis,Menten (1913) - Briggs,Haldane (1925) studies rate
laws for simple enzymatic reaction (simplified).
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1926 Kluyver & Donker's "unity of biochemistry" principle
1930-40s Krebs characterizes citric acid cycle
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1945 Norman H. Horowitz First Model of Metabolic Evolution.
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Melvin Calvin
1911-97 NP 61
1930-40s Calvin characterizes carbon path in
photosynthesis
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1961 The Operon model of Gene Regulation
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Jacques Monod
François Jacob
1920-
NP1965
1910 -76 NP1965
mRNA
Factor A
mRNA
A
B
A
B
Factor B
1964 Goodwin First mathematical analysis of Operon model of Gene
protein
promoter
dX mRNA
 f (X prot )  c mRNA X mRNA
dt
mRNA
Gene
dX prot
 kXmRNA  c prot X prot
dt
1969- exploration of the dynamics of Boolean Networks
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Stuart Kauffman
Time 1
Factor A
Time 3
Time T
Gene 1
mRNA
mRNA
mRNA
Time 2
Factor B
Gene 2
Gene 3
Gene 4
Factor C
Remade from Somogyi & Sniegoski,96. F2
Gene n
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Michael Savageau
1969- Biochemical Systems Theory
X0
X0' = 0 X0g00X1g01 - 0 X0 h00 X1 h01
X1' = 1 X0g10X1g11 - 1 X0 h10 X1 h11
X1
1973-4..: First articles on MCA - metabolic control analysis
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Two classes of theorems
Control Summation
Connectivity
E, n
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1995:Arkin, McAdams, Ross: Stochastic Models of Gene Regulation
protein
promoter
mRNA
Gene
1995-2005
Metabolic Pathways, Flux Analysis and Genome Annotation
Palsson
Schilling
Fell
Schuster
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•Kinetic Model Fitting Westerhoff
•The phenotype of a network (Omholt, Plathe, …)
•Network Comparison: Labeling of edges/nodes (homology)
•Spatial Information
•Network inference
•Designed/Evolved Network
•Modularity
•Robustness
•Evolvability
•Integration of Networks
•Designed Networks.
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Biological sub-cellular Networks
•Signal Transduction Networks
•Protein Interaction Networks
•Alternative Splicing Graph
Biological cellular and supra-cellular Networks
Cellular
Above the Cell
•Neural Networks
•Immunological Networks
•Disease Networks
•Genealogical Networks
Non-biological Networks
•Social Networks
•The Internet
•Collaboration Networks
•Semantic Networks
•Publications and references
Today’s Schedule
1.00pm
Jotun Hein:Introduction and Biology of Networks
1.20pm
Chris Holmes: Inference of Networks
1.35pm
Andrea Rocco: Modelling structure and function in complex networks
1.50pm
Gesine Reinert: Statistics for small-world networks
2.10pm
Michael Stumpf: Comparative Biology of Networks
2.25-2.45pm
mini-BREAK
2.45pm
Imre Vastrik:The Reactome
3.15 pm
Hector Keun:Metabonomics and modeling metabolic networks.
3.45-4.15pm
maxi-BREAK
4.15 pm
Philip Bang: Machine Learning for Systems Biology
4.45pm
Gail Preston:Evolutionary Modelling of Nitrogen Metabolism in Pseudomonas
5.05–5.20pm
Neil Johnson:Complex Agent-Based Dynamical Networks