State Transitions
Many 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 define a metric based on delayed correlation to infer state transition patterns between states directly from stable steady states. The method has been applied to the cell cycle circuit, the repressilator circuit, and an induced toggle switch circuit.
Reference:
A. Katebi, V. Kohar, M. Lu. (2020) Random Parametric Perturbations of Gene Regulatory Circuit Uncover State Transitions in Cell Cycle. iScience. 23(6): 101150 PDF