CABEAN

CABEAN computes control interventions in asynchronous Boolean networks to identify perturbations of genes or molecular interactions that drive gene regulatory networks from a source attractor to a target attractor for applications in direct cell reprogramming and transdifferentiation.

Key Features:

• Asynchronous Boolean network control: Operates on asynchronous Boolean network models to determine control interventions at the network level.
• Gene regulatory network modeling: Uses the Boolean networks framework to represent gene regulatory networks and their cellular dynamics.
• Efficacious node identification: Identifies nodes representing genes or molecular interactions whose perturbations can drive transitions from a source attractor to a target attractor.
• Six source-target control problems: Addresses six distinct source-target control problem formulations to cover different reprogramming scenarios.
• Multiple control strategies: Implements multiple control strategies tailored to the six source-target control problems.
• Integration of experimental constraints: Incorporates practical experimental constraints into the control problem formulations.
• Generation of control sets: Produces a rich set of control sets (candidate intervention combinations) for selection and experimental validation.

Scientific Applications:

• Direct cell reprogramming: Identifies interventions to convert a source cell type attractor into a desired target cell type attractor.
• Transdifferentiation: Determines perturbations that enable direct conversion between differentiated cell types via network control.
• Tissue engineering: Guides selection of molecular interventions to achieve target cellular states relevant for engineered tissues.
• Regenerative medicine: Supports discovery of control strategies to restore or reprogram cell states for regenerative therapies.

Methodology:

Models gene regulatory networks as asynchronous Boolean networks, identifies nodes (genes or molecular interactions) whose perturbations drive transitions from source attractors to target attractors, solves six distinct source-target control problems using multiple control strategies while integrating experimental constraints, and generates sets of candidate control interventions.