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The Diversity and Integration of Biological Network Motifs

The Diversity and Integration of Biological Network Motifs. Seminars in Bioinformatics Martin Akerman 31/03/08. Biological Networks. Questions: Which are the most common motifs among biological networks? How do these motifs interrelate?. Biological Network motifs.

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The Diversity and Integration of Biological Network Motifs

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  1. The Diversity and Integration of Biological Network Motifs Seminars in Bioinformatics Martin Akerman 31/03/08

  2. Biological Networks • Questions: • Which are the most common motifs among biological networks? • How do these motifs interrelate?

  3. Biological Network motifs Single Input Model (SIM) Autoregulation (AR) Dense Overlapping Regulon (DOR) Feed Forward Loops (FFL) Regulating and Regulated Feedback Loops (RFL) BiFan Diamond Cascade

  4. Single Input Model (SIM) • 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).

  5. Single Input Model (SIM) • The SIMs can generate temporal programs of expression: Last-In First-Out (LIFO) Program

  6. LIFO Program in Arginine Biosynthesis

  7. First-In First-Out (FIFO) Program Kxz1 Kxz2 [X] Kxz3 Kxz3 Kxz2 [Y] Kxz1 [Z1] [Z2] [Z3] Kxz1>Kxz2>Kxz3 K’xz1<K’xz2<K’xz3 Time

  8. FIFO program in Flagella Biosynthesis

  9. FIFO program is governed by a FFL

  10. Multi-input FFL in Neuronal Networks Noxious Chemicals Nose Touch Nose Touch FLP ASH AVD AVA Backward movement

  11. Multi-input FFL in Neuronal Networks The change in voltage of Y X1 X2 The change in voltage of Z Y Z

  12. Interlocking Feed forward loops Bacillus Subtilis sporuation process

  13. Dense Overlapping Regulon (DOR)

  14. FFLs and SIMs are integrated within DORs How do Network Motifs Integrate? Where are the XYZ ? A Master Regulators Layer (lots of Auto-Reg.) A single DOR Layer The E.coli Transcription Network (partial)

  15. Signal Transduction Cascades

  16. Popular Motifs in Signal Transduction Cascades X X1 X2 Y1 Y2 Y1 Y2 Z BiFan Diamond Generalization of DOR X1 X2 X X1 X2 Multi-layer Perceptrons (multi-DORs) Y1 Y2 Y1 Y2 Y1 Y2 Z Z1 Z2 Z1 Z2

  17. Multi Layer Perceptorns in Signal Transduction Cascades X2 X2 P X1 X1 P Y2 Y2 P Y1 Y1 P Z2 Z2 P Z1 Z1 P

  18. Dynamics of Signal Transduction Cascades X1 X2 Y At Steady State X2 0.5 , Activation Threshold X1 0.5

  19. Dynamics of Signal Transduction Cascades “AND” gate “OR” gate X1 X2 X1 X2 Y Y X2 X2 0.5 0.5 X1 0.5 X1 0.5

  20. Dynamics of Signal Transduction Cascades “OR” gate X1 X2 1.5 1.5 0.7 0.7 Y1 Y2 Z Y1 Y2 2 2 Z “AND” gate X1 X2 1.5 1.5 0.7 0.7 Y1 Y2 Z Y1 Y2 0.6 0.6 Z

  21. Dynamics of Signal Transduction Cascades X1 X2 1.5 1.5 0.7 0.7 Y1 Y2 Z Y1 Y2 2 -3 Z X1 X2 1.7 0.7 1.7 0.7 Z Y1 Z Y2 Y1 Y2 2 -3 Z

  22. Dynamics of Signal Transduction Cascades • Multi-layer perceptrons can show: • Discrimination: the ability to accurately recognize certain stimuli patterns. • Generalization: the ability to fill the gaps in partial stimuli patterns. • Graceful degradation: damage to elements of the perceptron or it connections does not bring the network to crashing halt

  23. Feed Back Loops Z X Y X Y • X transcriptionally activates X. • Y inhibits X. • Z transcriptionally activates X and Y • X forms a complex with Y. • X phosphorylates Y. Power Heater Temperature - (Fast) Protein-Protein Interactions Thermostat (Slow) Transcriptional Interactions

  24. Feed Back Loops Produce Oscillation Cdc20 oscillator controls Cell Cycle Mutation of the Drosophila CWO gene

  25. Developmental Transcription Netwroks The TF expression profile in a developing Drosophila embryo

  26. Developmental Transcription Netwroks Two-node Feedback Loops X Y X Y • Both X AND Y are ON at the same time. • Genes regulated by X and Y belong to the same tissue (or strip). • X OR Y is ON at a given time. • Genes regulated by X and Y belong to different tissues (strips).

  27. Developmental Transcription Netwroks Regulating Feedback Loops X Y X Y Z Z Double Negative Loops Double Positive Loops Z Z X Y X Y Regulated Feedback Loops

  28. Developmental Transcription Netwroks Regulated Feedback Loops as a Memory Element

  29. Developmental Transcription Netwroks Cascades X Y Z X Y Z

  30. 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). • Motifs within a network may be arranged in organized structures (perceptrons, interlocking FFL). • Different kinds of network may interact to generate regulation

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