A necessary condition for non-monotonic dose response, with an application to a kinetic proofreading model -- Extended version
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arXiv
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| Autori principali: | , |
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| Natura: | Preprint |
| Pubblicazione: |
2024
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| _version_ | 1866910580171866112 |
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| author | Yu, Polly Y. Sontag, Eduardo D. |
| author_facet | Yu, Polly Y. Sontag, Eduardo D. |
| contents | 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. |
| format | Preprint |
| id |
arxiv_https___arxiv_org_abs_2403_13862 |
| institution | arXiv |
| publishDate | 2024 |
| record_format | arxiv |
| spellingShingle | A necessary condition for non-monotonic dose response, with an application to a kinetic proofreading model -- Extended version Yu, Polly Y. Sontag, Eduardo D. Molecular Networks Optimization and Control 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. |
| title | A necessary condition for non-monotonic dose response, with an application to a kinetic proofreading model -- Extended version |
| topic | Molecular Networks Optimization and Control |
| url | https://arxiv.org/abs/2403.13862 |