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arXiv · 2403.13862

A necessary condition for non-monotonic dose response, with an application to a kinetic proofreading model -- Extended version

Polly Y. Yu·Eduardo D. Sontag
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Abstract

Steady state nonmonotonic ("biphasic") dose responses are often observed in experimental biology, which raises the control-theoretic question of identifying which possible mechanisms might underlie such behaviors. It is well known that the presence of an incoherent feedforward loop (IFFL) in a network may give rise to a nonmonotonic response. It has been conjectured that this condition is also necessary, i.e. that a nonmonotonic response implies the existence of an IFFL. In this paper, we show that this conjecture is false, and in the process prove a weaker version: that either an IFFL must exist or both a positive feedback loop and a negative feedback loop must exist. Towards this aim, we give necessary and sufficient conditions for when minors of a symbolic matrix have mixed signs. Finally, we study in full generality when a model of immune T-cell activation could exhibit a steady state nonmonotonic dose response.

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Polly Y. Yu, Eduardo D. Sontag. 2024-03-20. A necessary condition for non-monotonic dose response, with an application to a kinetic proofreading model -- Extended version. https://arxiv.org/abs/2403.13862

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