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Page 1: OUTLINE Introduction to Systems Biology Biological Networks
Page 2: OUTLINE Introduction to Systems Biology Biological Networks

OUTLINE

Introduction to Systems Biology Biological Networks

Page 3: OUTLINE Introduction to Systems Biology Biological Networks

Introduction to Systems Biology

First introduced in 1934, By Austrian biologist Ludwig von

Bertalanffy, He applied the general system theory to

biology.

Page 4: OUTLINE Introduction to Systems Biology Biological Networks

Introduction to Systems Biology

To fully understand the functioning of cellular processes, whole cells, organisms, and even organisms:– it is not enough to simply assign functions to

individual genes, proteins, and other cellular organisms,

– we need an integrated way to look at the dynamic networks representing the interactions of components.

Page 5: OUTLINE Introduction to Systems Biology Biological Networks

Introduction to Systems Biology

What is a System:– dynamics of its components,– interaction of components,– we need modeling to understand the mechanism.

Page 6: OUTLINE Introduction to Systems Biology Biological Networks

Introduction to Systems Biology

The higher-order properties and functions that arise from the interaction of the parts of a system are called emergent properties.– human brain can thought by the interaction of

brain cells,– a single brain cell is incapable of the property of

thought.

Page 7: OUTLINE Introduction to Systems Biology Biological Networks

Introduction to Systems Biology

Page 8: OUTLINE Introduction to Systems Biology Biological Networks

Introduction to Systems Biology

A number of web sites make available information about the interacting proteins in a particular pathway.

Page 9: OUTLINE Introduction to Systems Biology Biological Networks

Introduction to Systems Biology

the glycolytic patway

Page 10: OUTLINE Introduction to Systems Biology Biological Networks

Introduction to Systems Biology

The interactions in networks can be represented as DEs:– all the interactions between components in a

model need to be represented mathematically,– differential equations are used for

representation of interactions

Page 11: OUTLINE Introduction to Systems Biology Biological Networks

Introduction to Systems Biology

Example:

Page 12: OUTLINE Introduction to Systems Biology Biological Networks

Introduction to Systems Biology

Example:

Page 13: OUTLINE Introduction to Systems Biology Biological Networks

Introduction to Systems Biology

Another example (Tumor Growth Simulation):

Page 14: OUTLINE Introduction to Systems Biology Biological Networks

Biological Networks

the glycolytic patway

Page 15: OUTLINE Introduction to Systems Biology Biological Networks

Biological Networks

E. coli:– a single cell,– amazing technology.

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Biological Networks

Gene regulation:– Activators increase gene production

– Repressors decrease gene production

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Biological Networks

Gene regulation:– Negative feedback loop:

– Positive feedback loop:

Page 18: OUTLINE Introduction to Systems Biology Biological Networks

Biological Networks

Nodes are proteins (or genes)

Page 19: OUTLINE Introduction to Systems Biology Biological Networks

Biological Networks

Nodes are proteins (or genes)

Page 20: OUTLINE Introduction to Systems Biology Biological Networks

Biological Networks

Network motifs:– Subgraphs: which occur in the real network

significantly more than in a suitable random ensemble of network.

Page 21: OUTLINE Introduction to Systems Biology Biological Networks

Biological Networks

Network motifs:– 3-node subgraphs:

Page 22: OUTLINE Introduction to Systems Biology Biological Networks

Biological Networks

Network motifs:– 4-node subgraphs:

Page 23: OUTLINE Introduction to Systems Biology Biological Networks

Biological Networks

Network motifs:– 5-node subgraphs:

9 364 possible subgraphs

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Biological Networks

Network motifs:– 6-node subgraphs:

1 530 843 possible subgraphs

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Biological Networks

Find network motifs (ALGORITHM):

Page 26: OUTLINE Introduction to Systems Biology Biological Networks

Biological Networks

Find network motifs (EXAMPLE):– Network motifs in E. coli

Page 27: OUTLINE Introduction to Systems Biology Biological Networks

Biological Networks

Find network motifs (EXAMPLE):– Network motifs in E. coli– only one 3-node network motif is significant.

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Biological Networks

Network motifs:– Network motifs are functional building blocks of

these information processing networks.– Each motif can be studied theoretically and

experimentally.

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Biological Networks

Other networks:– enzyme – lignad

metabolic pathways

– protein – protein cell signaling pathways,

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Biological Networks

Pathways:– Pathways are subsets of networks,– Pathways are networks of interactions,– Pathways are related to a known physiological

process or complete function.

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Biological Networks

Pathways EXAMPLE:

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Biological Networks

Problems:– Source of interaction data is basicly the

experiments,– But in these experiments:

low quality, false positive, false negative.

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Biological Networks

Problems SOLUTION:– Probabilistic networks.

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Biological Networks

Other Problems:– Network reliability:

What is the probability that some path of functioning wires connects two terminals at a given time?

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Biological Networks

Other Problems:– Finding the best simple path (each vertex is

visited once, no cycles) of length k starting from a given node in the graph:

Page 36: OUTLINE Introduction to Systems Biology Biological Networks

References

M. Zvelebil, J. O. Baum, “Understanding Bioinformatics”, 2008, Garland Science

Andreas D. Baxevanis, B.F. Francis Ouellette, “Bioinformatics: A practical guide to the analysis of genes and proteins”, 2001, Wiley.

Barbara Resch, “Hidden Markov Models - A Tutorial for the Course Computational Intelligence”, 2010.

Wang, Z., Zhang, L., Sagotsky, J., Deisboeck. T. S. (2007), Simulating non-small cell lung cancer with a multiscale agent-based model, Theoretical Biology & Medical Modelling.