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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.
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The Dynamics of Canalizing Boolean Networks
Boolean networks are a popular modeling framework in computational biology to capture the dynamics of molecular networks, such as gene regulatory networks. It has been observed that many published models of such networks are defined by regulatory rules driving the dynamics that have certain so-called canalizing properties. In this paper, we investigate the dynamics of a random Boolean network with such properties using analytical methods and simulations. From our simulations, we observe that Boolean networks with higher canalizing depth have generally fewer attractors, the attractors are smaller, and the basins are larger, with implications for the stability and robustness of the models. These properties are relevant to many biological applications. Moreover, our results show that, from the standpoint of the attractor structure, high canalizing depth, compared to relatively small positive canalizing depth, has a very modest impact on dynamics. Motivated by these observations, we conduct mathematical study of the attractor structure of a random Boolean network of canalizing depth one (i.e., the smallest positive depth). For every positive integer ℓ , we give an explicit formula for the limit of the expected number of attractors of length ℓ in an n -state random Boolean network as n goes to infinity.
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- PAR ID:
- 10162532
- Date Published:
- Journal Name:
- Complexity
- Volume:
- 2020
- ISSN:
- 1076-2787
- Page Range / eLocation ID:
- 1 to 14
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1155/2020/3687961
