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?
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!
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
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[
Multi-input FFL in Neuronal Networks
FLP ASH
AVD
AVA
Nose Touch Noxious ChemicalsNose Touch
Backward movement
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.)