Edgetic perturbations to eliminate fixed-point attractors in Boolean regulatory networks

Colin Campbell, Reka Z. Albert

Research output: Contribution to journalArticle

Abstract

The dynamics of complex biological networks may be modeled in a Boolean framework, where the state of each system component is either abundant (ON) or scarce/absent (OFF), and each component's dynamic trajectory is determined by a logical update rule involving the state(s) of its regulator(s). It is possible to encode the update rules in the topology of the so-called expanded graph, analysis of which reveals the long-term behavior, or attractors, of the network. Here, we develop an algorithm to perturb the expanded graph (or, equivalently, the logical update rules) to eliminate stable motifs: subgraphs that cause a subset of components to stabilize to one state. Depending on the topology of the expanded graph, these perturbations lead to the modification or loss of the corresponding attractor. While most perturbations of biological regulatory networks in the literature involve the knockout (fixing to OFF) or constitutive activation (fixing to ON) of one or more nodes, we here consider edgetic perturbations, where a node's update rule is modified such that one or more of its regulators is viewed as ON or OFF regardless of its actual state. We apply the methodology to two biological networks. In a network representing T-LGL leukemia, we identify edgetic perturbations that eliminate the cancerous attractor, leaving only the healthy attractor representing cell death. In a network representing drought-induced closure of plant stomata, we identify edgetic perturbations that modify the single attractor such that stomata, instead of being fixed in the closed state, oscillates between the open and closed states.

Original languageEnglish (US)
Article number023130
JournalChaos
Volume29
Issue number2
DOIs
StatePublished - Feb 1 2019

Fingerprint

Boolean Networks
Regulatory Networks
Attractor
Eliminate
Fixed point
Topology
Perturbation
Biological Networks
perturbation
Update
Drought
Cell death
Stomata
Regulator
Chemical activation
regulators
Trajectories
fixing
Graph in graph theory
topology

All Science Journal Classification (ASJC) codes

  • Statistical and Nonlinear Physics
  • Mathematical Physics
  • Physics and Astronomy(all)
  • Applied Mathematics

Cite this

@article{02968340b6324e4da830f83ee29561e0,
title = "Edgetic perturbations to eliminate fixed-point attractors in Boolean regulatory networks",
abstract = "The dynamics of complex biological networks may be modeled in a Boolean framework, where the state of each system component is either abundant (ON) or scarce/absent (OFF), and each component's dynamic trajectory is determined by a logical update rule involving the state(s) of its regulator(s). It is possible to encode the update rules in the topology of the so-called expanded graph, analysis of which reveals the long-term behavior, or attractors, of the network. Here, we develop an algorithm to perturb the expanded graph (or, equivalently, the logical update rules) to eliminate stable motifs: subgraphs that cause a subset of components to stabilize to one state. Depending on the topology of the expanded graph, these perturbations lead to the modification or loss of the corresponding attractor. While most perturbations of biological regulatory networks in the literature involve the knockout (fixing to OFF) or constitutive activation (fixing to ON) of one or more nodes, we here consider edgetic perturbations, where a node's update rule is modified such that one or more of its regulators is viewed as ON or OFF regardless of its actual state. We apply the methodology to two biological networks. In a network representing T-LGL leukemia, we identify edgetic perturbations that eliminate the cancerous attractor, leaving only the healthy attractor representing cell death. In a network representing drought-induced closure of plant stomata, we identify edgetic perturbations that modify the single attractor such that stomata, instead of being fixed in the closed state, oscillates between the open and closed states.",
author = "Colin Campbell and Albert, {Reka Z.}",
year = "2019",
month = "2",
day = "1",
doi = "10.1063/1.5083060",
language = "English (US)",
volume = "29",
journal = "Chaos",
issn = "1054-1500",
publisher = "American Institute of Physics Publising LLC",
number = "2",

}

Edgetic perturbations to eliminate fixed-point attractors in Boolean regulatory networks. / Campbell, Colin; Albert, Reka Z.

In: Chaos, Vol. 29, No. 2, 023130, 01.02.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Edgetic perturbations to eliminate fixed-point attractors in Boolean regulatory networks

AU - Campbell, Colin

AU - Albert, Reka Z.

PY - 2019/2/1

Y1 - 2019/2/1

N2 - The dynamics of complex biological networks may be modeled in a Boolean framework, where the state of each system component is either abundant (ON) or scarce/absent (OFF), and each component's dynamic trajectory is determined by a logical update rule involving the state(s) of its regulator(s). It is possible to encode the update rules in the topology of the so-called expanded graph, analysis of which reveals the long-term behavior, or attractors, of the network. Here, we develop an algorithm to perturb the expanded graph (or, equivalently, the logical update rules) to eliminate stable motifs: subgraphs that cause a subset of components to stabilize to one state. Depending on the topology of the expanded graph, these perturbations lead to the modification or loss of the corresponding attractor. While most perturbations of biological regulatory networks in the literature involve the knockout (fixing to OFF) or constitutive activation (fixing to ON) of one or more nodes, we here consider edgetic perturbations, where a node's update rule is modified such that one or more of its regulators is viewed as ON or OFF regardless of its actual state. We apply the methodology to two biological networks. In a network representing T-LGL leukemia, we identify edgetic perturbations that eliminate the cancerous attractor, leaving only the healthy attractor representing cell death. In a network representing drought-induced closure of plant stomata, we identify edgetic perturbations that modify the single attractor such that stomata, instead of being fixed in the closed state, oscillates between the open and closed states.

AB - The dynamics of complex biological networks may be modeled in a Boolean framework, where the state of each system component is either abundant (ON) or scarce/absent (OFF), and each component's dynamic trajectory is determined by a logical update rule involving the state(s) of its regulator(s). It is possible to encode the update rules in the topology of the so-called expanded graph, analysis of which reveals the long-term behavior, or attractors, of the network. Here, we develop an algorithm to perturb the expanded graph (or, equivalently, the logical update rules) to eliminate stable motifs: subgraphs that cause a subset of components to stabilize to one state. Depending on the topology of the expanded graph, these perturbations lead to the modification or loss of the corresponding attractor. While most perturbations of biological regulatory networks in the literature involve the knockout (fixing to OFF) or constitutive activation (fixing to ON) of one or more nodes, we here consider edgetic perturbations, where a node's update rule is modified such that one or more of its regulators is viewed as ON or OFF regardless of its actual state. We apply the methodology to two biological networks. In a network representing T-LGL leukemia, we identify edgetic perturbations that eliminate the cancerous attractor, leaving only the healthy attractor representing cell death. In a network representing drought-induced closure of plant stomata, we identify edgetic perturbations that modify the single attractor such that stomata, instead of being fixed in the closed state, oscillates between the open and closed states.

UR - http://www.scopus.com/inward/record.url?scp=85062110312&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85062110312&partnerID=8YFLogxK

U2 - 10.1063/1.5083060

DO - 10.1063/1.5083060

M3 - Article

C2 - 30823730

AN - SCOPUS:85062110312

VL - 29

JO - Chaos

JF - Chaos

SN - 1054-1500

IS - 2

M1 - 023130

ER -