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Large programs of dynamic gene expression, like cell cyles and circadian rhythms, are controlled by a relatively small “core” network of transcription factors and post-translational modifiers, working in concerted mutual regulation. Recent work suggests that system-independent, quantitative features of the dynamics of gene expression can be used to identify core regulators. We introduce an approach of iterative network hypothesis reduction from time-series data in which increasingly complex features of the dynamic expression of individual, pairs, and entire collections of genes are used to infer functional network models that can produce the observed transcriptional program. The culmination of our work is a computational pipeline, I terative N etwork H ypoth e sis Re ductio n from T emporal Dynamics (Inherent dynamics pipeline), that provides a priority listing of targets for genetic perturbation to experimentally infer network structure. We demonstrate the capability of this integrated computational pipeline on synthetic and yeast cell-cycle data. 

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. 

Abstract This work is motivated by the following question in data-driven study of dynamical systems: given a dynamical system that is observed via time series of persistence diagrams that encode topological features of snapshots of solutions, what conclusions can be drawn about solutions of the original dynamical system? We address this challenge in the context of an N dimensional system of ordinary differential equation defined in $${\mathbb {R}}^N$$ R N . To each point in $${\mathbb {R}}^N$$ R N (e.g. an initial condition) we associate a persistence diagram. The main result of this paper is that under this association the preimage of every persistence diagram is contractible. As an application we provide conditions under which multiple time series of persistence diagrams can be used to conclude the existence of a fixed point of the differential equation that generates the time series.