Robust network clocks: design of genetic oscillators as a complex combinatorial optimization problem.

Complex combinatorial optimization can be used to design network systems having desired dynamics and that are robust against structural perturbations. Here genetic networks exhibiting limit-cycle oscillations with prescribed periods and, furthermore, that are robust against the deletion of links and nodes or the application of noise are constructed. Large ensembles of robust genetic clocks with different periods could thus be obtained, and some of their statistical properties have been investigated. Similar methods can be used to design robust network oscillators of various origins.