文章基本信息

标题：Random Parametric Perturbations of Gene Regulatory Circuit Uncover State Transitions in Cell Cycle
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作者：Ataur Katebi ; Vivek Kohar ; Mingyang Lu 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2020
卷号：23
期号：6
页码：1-68
DOI：10.1016/j.isci.2020.101150
语种：English
出版社：Elsevier
摘要：SummaryMany biological processes involve precise cellular state transitions controlled by complex gene regulation. Here, we use budding yeast cell cycle as a model system and explore how a gene regulatory circuit encodes essential information of state transitions. We present a generalized random circuit perturbation method for circuits containing heterogeneous regulation types and its usage to analyze both steady and oscillatory states from an ensemble of circuit models with random kinetic parameters. The stable steady states form robust clusters with a circular structure that are associated with cell cycle phases. This circular structure in the clusters is consistent with single-cell RNA sequencing data. The oscillatory states specify the irreversible state transitions along cell cycle progression. Furthermore, we identify possible mechanisms to understand the irreversible state transitions from the steady states. We expect this approach to be robust and generally applicable to unbiasedly predict dynamical transitions of a gene regulatory circuit.Graphical AbstractDisplay OmittedHighlights•A core gene regulatory circuit encodes irreversible cell cycle state transitions•Statistical analysis on randomly generated ODE models elucidates circuit dynamics•Steady states specify cell cycle phases, and oscillatory states, their transitions•State transition patterns inferred by delayed correlation and parameter perturbationCell Biology; Systems Biology; In Silico Biology