Searching bifurcations in high-dimensional parameter space via a   feedback loop breaking approach
  Bifurcations leading to complex dynamical behaviour of non-linear systems are often encountered when the characteristics of feedback circuits in the system are varied. In systems with many unknown or varying parameters, it is an interesting, but difficult problem to find parameter values for which specific bifurcations occur. In this paper, we develop a loop breaking approach to evaluate the influence of parameter values on feedback circuit characteristics. This approach allows a theoretical classification of feedback circuit characteristics related to possible bifurcations in the system. Based on the theoretical results, a numerical algorithm for bifurcation search in a possibly high-dimensional parameter space is developed. The application of the proposed algorithm is illustrated by searching for a Hopf bifurcation in a model of the mitogen activated protein kinase (MAPK) cascade, which is a classical example for biochemical signal transduction. 
Steffen Waldherr and Frank Allg\"ower