title: Control of Stochastic and Induced Switching in Biophysical Networks.
abstract: Noise caused by fluctuations at the molecular level is a fundamental part of intracellular processes. While the response of biological systems to noise has been studied extensively, there has been limited understanding of how to exploit it to induce a desired cell state. Here we present a scalable, quantitative method based on the Freidlin-Wentzell action to predict and control noise-induced switching between different states in genetic networks that, conveniently, can also control transitions between stable states in the absence of noise. We apply this methodology to models of cell differentiation and show how predicted manipulations of tunable factors can induce lineage changes, and further utilize it to identify new candidate strategies for cancer therapy in a cell death pathway model. This framework offers a systems approach to identifying the key factors for rationally manipulating biophysical dynamics, and should also find use in controlling other classes of noisy complex networks.
authors.affiliation: Department of Engineering Sciences and Applied Mathematics, Northwestern University, Evanston, IL 60208, USA ; Northwestern Physical Sciences-Oncology Center, Northwestern University, Evanston, IL 60208, USA.
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Wells
authors.affiliation: Department of Engineering Sciences and Applied Mathematics, Northwestern University, Evanston, IL 60208, USA ; Northwestern Physical Sciences-Oncology Center, Northwestern University, Evanston, IL 60208, USA ; Northwestern Institute on Complex Systems, Northwestern University, Evanston, IL 60208, USA.
authors.forename: William L
authors.initials: WL
authors.lastname: Kath
authors.affiliation: Northwestern Physical Sciences-Oncology Center, Northwestern University, Evanston, IL 60208, USA ; Northwestern Institute on Complex Systems, Northwestern University, Evanston, IL 60208, USA ; Department of Physics and Astronomy, Northwestern University, Evanston IL, 60208, USA.
authors.forename: Adilson E
authors.initials: AE
authors.lastname: Motter
keywords: Biological Physics; Complex Systems; Nonlinear Dynamics