Rational design of complex phenotype via network models

DOI10.1371/JOURNAL.PCBI.1009189arXiv2010.03803WikidataQ113309283 ScholiaQ113309283MaRDI QIDQ6350797FDOQ6350797

Authors: Marcio Gameiro, Tomáš Gedeon, Shane Kepley, K. Mischaikow 

Publication date: 8 October 2020

Abstract: We demonstrate a modeling and computational framework that allows for rapid screening of thousands of potential network designs for particular dynamic behavior. To illustrate this capability we consider the problem of hysteresis, a prerequisite for construction of robust bistable switches and hence a cornerstone for construction of more complex synthetic circuits. We evaluate and rank most three node networks according to their ability to robustly exhibit hysteresis where robustness is measured with respect to parameters over multiple dynamic phenotypes. Focusing on the highest ranked networks, we demonstrate how additional robustness and design constraints can be applied. We compare our results to more traditional methods based on specific parameterization of ordinary differential equation models and demonstrate a strong qualitative match at a small fraction of the computational cost.

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