A yeast cell cycle pulse generator model shows consistency with multiple oscillatory and checkpoint mutant datasets

DOI10.1016/J.MBS.2023.109102MaRDI QIDQ6154137zbMATH OpenOpenAlexFDO

Authors Julian Fox, Breschine Cummins, Robert C. Moseley, Marcio Gameiro, Steven B. Haase

Publication date 14 February 2024

Published in Mathematical Biosciences (Search for Journal in Brave)

Full work available at URL https://arxiv.org/abs/2302.12946

zbMATH Keywords

cell cycledynamical systemsgene regulatory networksidentifiabilitymulti-level Boolean modeltranscription

Mathematics Subject Classification ID

Systems biology, networks (92C42) Microbiology (92C70)

Abstract: The regulatory mechanisms driving progression of the yeast cell cycle appears to be comprised of an interacting network of transcription factors (TFs), cyclin-dependent kinases (CDK) and ubiquitin ligases. From a systems perspective the controlling regulatory network must produce robust periodic behavior during proliferative phases, but have the capability to halt the cycle when unfavorable conditions trigger a checkpoint arrest. How the individual components of the network contribute to these dynamical phenotypes remains an open question. Here we evaluate the capability of a simplified network model hypothesized to contain key elements of the regulation of cell-cycle progression to reproduce observed transcriptomic behaviors. We match time-series data from both cycling and checkpoint arrested cells to the predictions of a relatively simple cell-cycle network model using an asynchronous multi-level Boolean approach. We show that this single network model, despite its simplicity, is capable of exhibiting dynamical behavior similar to the datasets in most cases, and where it does not, we identified hypotheses that suggest missing components of the network.

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Cites work

• Chaos in neural and gene networks with hard switching
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Cited in

(2)

• Generating synthetic signaling networks for in silico modeling studies
• Analytic solutions for the circadian oscillator characterize cycle dynamics and its robustness

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