Comprehensive Boolean model of the mammalian cell cyle control network

Published by Sizek et al. in 2019, this Boolean model encompasses 87 components representing different molecular species and cellular processes involved in the regulation of cell proliferation versus apoptosis for a generic human cell. The authors conceived this complex model as an association of different functional modules:
- Growth Signalling module (green nodes): incorportates growth signalling pathways driving cell cycle commitment, responsible for modeling the dynamics of PI3K, AKT1, MAPK and mTORC.
- Restriction Switch (blue nodes): responsible for commitment to DNA synthesis.
- Origin Licensing switch (yellow nodes): responsible for licensing and firing of replication origins.
- Phase Switch (pink nodes): responsible for modeling cell cycle progression (G2 -> M -> G1). The switch was expanded to incorporate for the role of Polo like kinase 1 (Plk1) during mitosis.
- Apoptosis Switch (red nodes): responsible for modeling cell survival versus apoptosis.
- Cellular processes (orange nodes): helps to identify the phenotypic state and include some regulatory mechanisms.
The resulting model reproduces hyperactive PI3K-driven cytokinesis failure and genome duplication and predicts the molecular drivers responsible for these failures by linking hyperactive PI3K to mis-regulation of Polo-like kinase 1 (Plk1) expression late in G2.