Biological control networks suggest the use of biomimetic sets for combinatorial therapies

Biology – Quantitative Biology – Molecular Networks

Scientific paper

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33 pages

Scientific paper

10.1371/journal.pone.0029374

Cells are regulated by networks of controllers having many targets, and targets affected by many controllers, but these "many-to-many" combinatorial control systems are poorly understood. Here we analyze distinct cellular networks (transcription factors, microRNAs, and protein kinases) and a drug-target network. Certain network properties seem universal across systems and species, suggesting the existence of common control strategies in biology. The number of controllers is ~8% of targets and the density of links is 2.5% \pm 1.2%. Links per node are predominantly exponentially distributed, implying conservation of the average, which we explain using a mathematical model of robustness in control networks. These findings suggest that optimal pharmacological strategies may benefit from a similar, many-to-many combinatorial structure, and molecular tools are available to test this approach.

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