Delayed decision-making in bistable models

Switching between two modes of operation is a common property of biological systems. In continuous-time differential equation models, this is often realised by bistability, i.e. the existence of two asymptotically stable steadystates. Several biological models are shown to exhibit delayed switching, with a pronounced transient phase, in particular for near-threshold perturbations. This study shows that this delay in switching from one mode to the other in response to a transient input is reflected in local properties of an unstable saddle point, which has a one dimensional unstable manifold with a significantly slower eigenvalue than the stable ones. Thus, the trajectories first approximatively converge to the saddle point, then linger along the saddle's unstable manifold before quickly approaching one of the stable equilibria. ©2010 IEEE.

Spatial models of bistability in biological collectives

We explore collective behavior in biological systems using a cooperative control framework. In particular, we study a hysteresis phenomenon in which a collective switches from circular to parallel motion under slow variation of the neighborhood size in which individuals tend to align with one another. In the case that the neighborhood radius is less than the circular motion radius, both circular and parallel motion can occur. We provide Lyapunov-based analysis of bistability of circular and parallel motion in a closed-loop system of self-propelled particles with coupled-oscillator dynamics. ©2007 IEEE.

Correct biological timing in Arabidopsis requires multiple light-signaling pathways.

Circadian oscillators provide rhythmic temporal cues for a range of biological processes in plants and animals, enabling anticipation of the day/night cycle and enhancing fitness-associated traits. We have used engineering models to understand the control principles of a plant's response to seasonal variation. We show that the seasonal changes in the timing of circadian outputs require light regulation via feed-forward loops, combining rapid light-signaling pathways with entrained circadian oscillators. Linear time-invariant models of circadian rhythms were computed for 3,503 circadian-regulated genes and for the concentration of cytosolic-free calcium to quantify the magnitude and timing of regulation by circadian oscillators and light-signaling pathways. Bioinformatic and experimental analysis show that rapid light-induced regulation of circadian outputs is associated with seasonal rephasing of the output rhythm. We identify that external coincidence is required for rephasing of multiple output rhythms, and is therefore important in general phase control in addition to specific photoperiod-dependent processes such as flowering and hypocotyl elongation. Our findings uncover a fundamental design principle of circadian regulation, and identify the importance of rapid light-signaling pathways in temporal control.

Nonparametric Bayesian sparse factor models with application to gene expression modeling

A nonparametric Bayesian extension of Factor Analysis (FA) is proposed where observed data $\mathbf{Y}$ is modeled as a linear superposition, $\mathbf{G}$, of a potentially infinite number of hidden factors, $\mathbf{X}$. The Indian Buffet Process (IBP) is used as a prior on $\mathbf{G}$ to incorporate sparsity and to allow the number of latent features to be inferred. The model's utility for modeling gene expression data is investigated using randomly generated data sets based on a known sparse connectivity matrix for E. Coli, and on three biological data sets of increasing complexity.

Comparison of the HSPF and HBV-INCA models: Crossing the Atlantic divide

Observation shows that the watershed-scale models in common use in the United States (US) differ from those used in the European Union (EU). The question arises whether the difference in model use is due to familiarity or necessity. Do conditions in each continent require the use of unique watershed-scale models, or are models sufficiently customizable that independent development of models that serve the same purpose (e.g., continuous/event- based, lumped/distributed, field-Awatershed-scale) is unnecessary? This paper explores this question through the application of two continuous, semi-distributed, watershed-scale models (HSPF and HBV-INCA) to a rural catchment in southern England. The Hydrological Simulation Program-Fortran (HSPF) model is in wide use in the United States. The Integrated Catchments (INCA) model has been used extensively in Europe, and particularly in England. The results of simulation from both models are presented herein. Both models performed adequately according to the criteria set for them. This suggests that there was not a necessity to have alternative, yet similar, models. This partially supports a general conclusion that resources should be devoted towards training in the use of existing models rather than development of new models that serve a similar purpose to existing models. A further comparison of water quality predictions from both models may alter this conclusion.

Global analysis of dynamical decision-making models through local computation around the hidden saddle

Bistable dynamical switches are frequently encountered in mathematical modeling of biological systems because binary decisions are at the core of many cellular processes. Bistable switches present two stable steady-states, each of them corresponding to a distinct decision. In response to a transient signal, the system can flip back and forth between these two stable steady-states, switching between both decisions. Understanding which parameters and states affect this switch between stable states may shed light on the mechanisms underlying the decision-making process. Yet, answering such a question involves analyzing the global dynamical (i.e., transient) behavior of a nonlinear, possibly high dimensional model. In this paper, we show how a local analysis at a particular equilibrium point of bistable systems is highly relevant to understand the global properties of the switching system. The local analysis is performed at the saddle point, an often disregarded equilibrium point of bistable models but which is shown to be a key ruler of the decision-making process. Results are illustrated on three previously published models of biological switches: two models of apoptosis, the programmed cell death and one model of long-term potentiation, a phenomenon underlying synaptic plasticity. © 2012 Trotta et al.

Oscillator models and collective motion

A description of the so called "particles with coupled oscillator dynamics" (PCOD) is presented which is used to model, analyze and synthesize collective motion. An oscillator model with spatial dynamics is presented to help describe how to design steering control laws while it is being used to study biological collectives. Lastly, both engineering and biological analysis were described.