Identifying inhibitors of epithelial–mesenchymal plasticity using a network topology-based approach

摘要

Schematic of network analysis strategy. The top part of the figure depicts RACIPE methodology of sampling random parameter sets (matrix P) and for each parameter set (each row in the matrix), randomly sampling multiple initial conditions to obtain steady states space and the phase space, i.e, information about monostable vs multi-stable parameter regions or phases. The bottom part of the figure depicts Boolean simulation method where for a given network, multiple initial conditions are randomly chosen and steady state space is obtained through asynchronous update. The center square depicts various possible topological perturbations done to the networks. EMP networks analysed in the study, namely, GRHL2 (top-left, 4 nodes, 7 edges), OVOL (top-center, 4 nodes, 9 edges), OCT4 (top-right, 5 nodes, 10 edges), NRF2 (bottom-left, 8 nodes, 16 edges), GRHL2wa (bottom-center, 4 nodes, 8 edges) and OVOLsi (bottom-right, 4 nodes, 8 edges).