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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. 

Since the seminal 1961 paper of Monod and Jacob, mathematical models of biomolecular circuits have guided our understanding of cell regulation. Model-based exploration of the functional capabilities of any given circuit requires systematic mapping of multidimensional spaces of model parameters. Despite significant advances in computational dynamical systems approaches, this analysis remains a nontrivial task. Here, we use a nonlinear system of ordinary differential equations to model oocyte selection in Drosophila , a robust symmetry-breaking event that relies on autoregulatory localization of oocyte-specification factors. By applying an algorithmic approach that implements symbolic computation and topological methods, we enumerate all phase portraits of stable steady states in the limit when nonlinear regulatory interactions become discrete switches. Leveraging this initial exact partitioning and further using numerical exploration, we locate parameter regions that are dense in purely asymmetric steady states when the nonlinearities are not infinitely sharp, enabling systematic identification of parameter regions that correspond to robust oocyte selection. This framework can be generalized to map the full parameter spaces in a broad class of models involving biological switches. 

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.