We analyze the stochastic dynamics of genetic regulatory networks using a system of nonlinear differential equations. The system of S-functions is applied to capture the role of RNA polymerase in the transcription-translation mechanism. Using probabilistic properties of chemical rate equations, we derive a system of stochastic differential equations which are analytically tractable despite the high dimension of the regulatory network. Using stationary solutions of these equations, we explain the apparently paradoxical results of some recent time-course microarray experiments where mRNA transcription levels are found to only weakly correlate with the corresponding transcription rates. Combining analytical and simulation approaches, we determine the set of relationships between the size of the regulatory network, its structural complexity, chemical variability, and spectrum of oscillations. In particular, we show that temporal variability of chemical constituents may decrease while complexity of the network is increasing. This finding provides an insight into the nature of "functional determinism" of such an inherently stochastic system as genetic regulatory network.

Spontaneous ultra-slow oscillations in brain signals are ubiquitous, although their source and function remain unknown. A new study now reports that this activity is correlated between functionally related areas across hemispheres in humans.

Organisms are equipped with regulatory systems that display a variety of dynamical behavior ranging from simple stable steady states, to switching and multistability, to oscillations. Earlier work has shown that oscillations in protein concentrations or gene expression levels are related to the presence of at least one negative feedback loop in the regulatory network. Here, we study the dynamics of a very general class of negative feedback loops. Our main result is that, when a single negative feedback loop dominates the dynamical behavior, the sequence of maxima and minima of the concentrations exhibit a pattern that uniquely identifies the interactions of the loop. This allows us to devise an algorithm to (i) test whether observed oscillating time series are consistent with a single underlying negative feedback loop, and if so, (ii) reconstruct the precise structure of the loop, i.e., the activating/repressing nature of each interaction. This method applies even when some variables are missing from the data set, or if the time series shows transients, like damped oscillations. We illustrate the relevance and the limits of validity of our method with three examples: p53-Mdm2 oscillations, circadian gene expression in cyanobacteria, and cyclic binding of cofactors at the estrogen-sensitive pS2 promoter.

We present a method that estimates the strength of neuronal oscillations at the cellular level, relying on autocorrelation histograms computed on spike trains. The method delivers a number, termed oscillation score, that estimates the degree to which a neuron is oscillating in a given frequency band. Moreover, it can also reliably identify the oscillation frequency and strength in the given band, independently of the oscillation in other frequency bands, and thus it can handle superimposed oscillations on multiple scales (theta, alpha, beta, gamma, etc.). The method is relatively simple and fast. It can cope with a low number of spikes, converging exponentially fast with the number of spikes, to a stable estimation of the oscillation strength. It thus lends itself to the analysis of spike-sorted single-unit activity from electrophysiological recordings. We show that the method performs well on experimental data recorded from cat visual cortex and also compares favorably to other methods. In addition, we provide a measure, termed confidence score, that determines the stability of the oscillation score estimate over trials.