Periodic Oscillations for Non Monotonic Smooth Negative Feedback Circuits
Résumé
Negative feedback circuits are a recurrent motif in regulatory biological networks, strongly linked
to the emergence of oscillatory behavior. The theoretical analysis of the existence of oscillations
is a difficult problem and typically involves many constraints on the monotonicity of the activity
functions. Here, we study the occurrence of periodic solutions in an n-dimensional class of nega-
tive feedback systems defined by smooth vector fields with a window of not necessarily monotonic
activity. Our method consists in circumscribing the smooth system by two piecewise linear ones,
each admitting a periodic solution. It can then be shown that the smooth negative feedback system
also has a periodic orbit, inscribed in the topological solid torus constructed from the two piecewise
linear orbits. The interest of our approach lies in first, adopting a general class of functions, with a
nonmonotonicity window, which permits a better fitting between theoretical models and experimen-
tal data, and second, establishing a more accurate location for the periodic solution, which is useful
for computational purposes in high dimensions. As an illustration, a model for the “repressilator”
synthetic system is analyzed and compared to real data, and shown to admit a periodic orbit, for a
range of activity functions.
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