HOW CELLS AVOID ERRORS IN METABOLIC AND SIGNALING NETWORKS

Abstract

We examine features of intracellular networks that make errors less probable and beneficial responses more probable. In a false negative (F-) error, a network does not respond to input. A network is reliable if it operates with a low probability of a F-error. Features that promote reliability include fewer reactions in sequence, more alternative pathways, no side reactions and negative feedback. In a false positive (F+) error, a network produces output without input. Here, a network is specific if it has a low probability of a F+error. Conjunctions of signals within or between pathways can improve specificity through sigmoid steady-state response curves, kinetic proofreading and checkpoints. Both reliability and specificity are important in networks that regulate the fate of a cell and in networks with hubs or modules, and this includes scale-free networks. Some networks discriminate among several inputs by responding to each input through a different combination of pathways.