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. 2025 Aug 22;11(34):eadw3995. doi: 10.1126/sciadv.adw3995

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Fig. 4. — (A) MAPK Boolean network. (B) Phenotype landscape under nominal conditions. The network exhibits 22 attractors and their corresponding basins in the nominal attractor landscape, each mapped to the nominal phenotype landscape. (C) Altered phenotype landscape under a LoF of PTEN. Almost all network states result in a no decision phenotype, which means none of the output nodes are ON. (D) Controlled phenotype landscape under inhibition of the PI3K-AKT signaling pathway. This intervention restores the nominal phenotype landscape. (E) Mechanism causing the distorted phenotype landscape. The alteration leads to activation of the PI3K-AKT signaling pathway, causing the inhibition of apoptosis and growth arrest nodes, resulting in the no decision phenotype. (F) Mechanism restoring the nominal phenotype landscape. Through inhibition of the PI3K-AKT signaling pathway, the flexibility of downstream apoptosis and growth arrest nodes is increased, enabling restoration of the nominal phenotype landscape. EGFR refers to the epidermal growth factor receptor.