Table 1.

Description of the theory methods used to identify controlling reactions in systems biology.

Methods	Authors	Network Styles	Dynamics	Input	Principle	Optimization
MDS	[29,134]	Undirected networks	Nonlinear	Adjacency matrix/ stoichiometric matrix	Optimization based on KNN and K-means using Euclidean distances and Bootstrap.	Linear discrete
Probabilistic controllability approach	[32]	Undirected networks	Nonlinear	Adjacency matrix/ stoichiometric matrix	Optimization based on the shortest path between nodes based on an index built using the correlation between reactions.	Linear continuous
DFVS	[135,136]	Directed networks	Nonlinear	Adjacency matrix/ stoichiometric matrix	Optimization based on nonlinear functions in a system of ODE that define the structure of the graph.	Nonlinear continuous/ discrete