Modularity, Retroactivity, and Structural Identification

Many reverse-engineering techniques in systems biology rely upon data on steady-state (or dynamic) perturbations – obtained from siRNA, gene knock-down or overexpression, kinase and phosphatase inhibitors, or other interventions – in order to understand the interactions between different ‘modules’ in a network. This paper first reviews one popular such technique, introduced by the author and collaborators, and also discusses why conclusions drawn from its (mis-)use may be misleading due to ‘retroactivity’ (impedance or load) effects. A theoretical result characterizing stoichiometric-induced steady-state retroactivity effects is given for a class of biochemical networks.

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