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Highly designable phenotypes and mutational buffers emerge from a systematic mapping between network topology and dynami PowerPoint Presentation
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Highly designable phenotypes and mutational buffers emerge from a systematic mapping between network topology and dynamic output. Nochomovitz & Li. The idea. Map network topologies to dynamical phenotypes. Designability = 2.

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slide1

Highly designable phenotypes and mutational buffers emerge from a systematic mapping between network topology and dynamic output

Nochomovitz & Li

the idea
The idea
  • Map network topologies to dynamical phenotypes

Designability = 2

The designability of a phenotype is defined as the number of topologies mapped onto it.

Designability = 1

dynamic phenotype
Dynamic phenotype

A limit cycle passing through a specific series of states or a particular fixed point.

A 5-cycle phenotype

(0001 0010  1001  0111  1010)

Network topology

updating rules
Updating rules

The time scales of the decay process and the activating or inhibitory processes are of equal order.

Rule 1:

Rule 2:

The decay process occurs on a much slower time scale than the activating or inhibitory processes.

comparison of the two rules
Comparison of the two rules

Under both rules, the strong, intermediate, and weakly designable phenotypes emerge consistently.

slide8

Designability spectrum of 4-cycles for 4-node networks

Mean designability of 4-cycles

0001  0010  0101 0011

what are the dynamical features of highly designable dynamical phenotypes
What are the dynamical features of highly designable dynamical phenotypes?

Case 1: (2 3 6 11)

0001  0010  0101  1010

Designability = 2500

Two classes of connections:

  • fully conserved connections
    • Correspond to a subnetwork module that is necessary to encode the disignable, stable phenotype.
  • variable connections
    • Control the transient dynamical flow.

Network with fully conserved connections

slide12

Case 2: (2 3 5 9 10)

(0001  0010  0100  1000  1001)

Designability = 250

slide13

Designability is independent of robustness

Robustness of a phenotype is measured by the number of transient states that flow toward the stable phenotype.

slide14

Mutational buffering:

The incorporation of a fourth node bearing specific connections to a set of genetically distinct three-node networks would trigger the three-node networks to acquire the same dynamical phenotype, despite possessing differing dynamical phenotypes as isolated three-node systems.

A scaffold refers to a fixed manner by which a fourth node interacts with a three-node subnetwork.

Buffering strength reports the ratio of designability of a dynamical phenotype observed on three-node subnetworks attached via scaffold to a fourth node, to that phenotype’s designability on isolated three-node networks.

slide15

An example of mutational buffer

Buffering strength = 11

Scaffold

summary
Summary
  • A small fraction of dynamical phenotypes possesses atypically high designabilities.
  • Highly designable dynamical phenotypes arise via the presence of a core of fully conserved network links.
  • No correlation exists between the stability of a dynamical phenotype and its designability.
  • Identification of mutational buffers, which act to suppress phenotypic variation through specific dynamical relationships to other genes.