Nodes Links Interaction A B Network Proteins Physical Interaction Protein-Protein A B Protein Interaction Metabolites Enzymatic conversion Protein-Metabolite A B Metabolic Transcription factor Target genes Transcriptional Interaction Protein-DNA A B Transcriptional Different types of Biological Networks
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Nodes
Links
Interaction
A
B
Network
Proteins
Physical Interaction
Protein-Protein
A
B
Protein Interaction
Metabolites
Enzymatic conversion
Protein-Metabolite
A
B
Metabolic
Transcription factorTarget genes
TranscriptionalInteraction
Protein-DNA
A
B
Transcriptional
Different types of Biological Networks
Finding Local properties of Biological Networks: Motifs
Network motifs are recurrent circuit elements.
We can study a network by looking at its parts (or motifs)
How many motifs are in the network?
Finding Local properties of Biological Networks: Motifs
Finding Local properties of Biological Networks: Motifs
Finding Local properties of Biological Networks: Motifs
Finding Local properties of Biological Networks: Motifs
What are these motifs? What biological relevance
they have?
Finding Local properties of Biological Networks: Motifs
Autoregulatory loop
The probability of having autoregulatory loops in a random network is ~ 0 !!!!.
Transcription networks: The regulation of a gene by its own product.
Protein-Protein interaction network: dimerization
Autoregulatory loop
Positive autoregulation Fast time-rise of protein
level
Negative autoregulation Stable steady state
time
[p
rote
in]
time
[p
rote
in]
What is the effect of Autoregulatory loops on gene expression levels?
Three-node loops
There are 13 possible structures with 3 nodes
Feed forward loop
X Y
Z
Feedback loop
X Y
Z
But in biological networks you can find only 2!
Feed Forward loops
Coherent Feed Forward Loop in flagella biosynthesis
A transcription coherent FFL motif ensuresThat flagella is synthesized only under appropriate conditions
Incoherent Feed Forward Loop in sporulation
A transcription incoherent FFL motif produces transient gene expression
Feed Back Loops in circadian expression
Feed back loops can produce oscillation in gene expression
X Y
Z The Drosophila CWO geneKadener 2007, Genes and Dev.
Power Heater
Thermostat
Temperature-
Single Input Module (SIMs)
The SIMs are common in sensory transcription networks:
Genes from a same Pathway (Arginine synthesis).
Genes responding to stress (DNA repair). Genes that assemble a same biological
machine (ribosomal genes).
Single Input Module (SIM)
The SIMs can generate temporal programs of expression:
Last-In First-Out (LIFO) Program
LIFO Program in ArginineBiosynthesis
First-In First-Out (FIFO) Program
Kxz1>Kxz2>Kxz3
K’xz1<K’xz2<K’xz3
Time
Kxz1
Kxz2
Kxz3
Kxz3
Kxz2
Kxz1
[X]
[Y]
]Z2[]Z3[
]Z1[
Where SIMs meet FFLs
Two interconnected SIMs can be viewed as a multi output FFL
Multi-input FFL in Neuronal Networks
FLP ASH
AVD
AVA
Nose Touch Noxious ChemicalsNose Touch
Backward movement
Dense Overlapping Regulon (DOR)
X1 X2
Y1 Y2
The DORs are more dense than randomly expected
How do Network Motifs Integrate?
The E.coli Transcription Network (partial)
A single DOR Layer
FFLs and SIMs are integrated within DORs
A Master Regulators Layer (lots of Auto-Reg.)
Summary
Network motifs can function in several biological processes (sensory systems,
development). different time scales (milliseconds, cell generations).
Network motifs can produce temporal programs (LIFO, FIFO, oscillation).
Different kinds of network may interact to generate regulation