Positive feedback produces broad distributions in maximum activation attained within a narrow time window in stochastic biochemical reactions.
Ontology highlight
ABSTRACT:
SUBMITTER: Das J
PROVIDER: S-EPMC3548829 | biostudies-other | 2013 Jan
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Complex feedback systems are ubiquitous in biology. Modeling such systems with mass action laws or master equations requires information rarely measured directly. Thus rates and reaction topologies are often treated as adjustable parameters. Here we present a general stochastic modeling method for small chemical and biochemical systems with emphasis on feedback systems. The method, Maximum Caliber (MaxCal), is more parsimonious than others in constructing dynamical models requiring fewer model assumptions and parameters to capture the effects of feedback. MaxCal is the dynamical analogue of Maximum Entropy. It uses average rate quantities and correlations obtained from short experimental trajectories to construct dynamical models. We illustrate the method on the bistable genetic toggle switch. To test our method, we generate synthetic data from an underlying stochastic model. MaxCal reliably infers the statistics of the stochastic bistability and other full dynamical distributions of the simulated data, without having to invoke complex reaction schemes. The method should be broadly applicable to other systems.
| S-EPMC3098004 | biostudies-literature
Project description:In this article, we introduce a likelihood-based estimation method for the stochastic volatility in mean (SVM) model with scale mixtures of normal (SMN) distributions (Abanto-Valle et al., 2012). Our estimation method is based on the fact that the powerful hidden Markov model (HMM) machinery can be applied in order to evaluate an arbitrarily accurate approximation of the likelihood of an SVM model with SMN distributions. The method is based on the proposal of Langrock et al. (2012) and makes explicit the useful link between HMMs and SVM models with SMN distributions. Likelihood-based estimation of the parameters of stochastic volatility models in general, and SVM models with SMN distributions in particular, is usually regarded as challenging as the likelihood is a high-dimensional multiple integral. However, the HMM approximation, which is very easy to implement, makes numerical maximum of the likelihood feasible and leads to simple formulae for forecast distributions, for computing appropriately defined residuals, and for decoding, i.e., estimating the volatility of the process.
| S-EPMC5621483 | biostudies-other
Project description:Noise is often indispensable to key cellular activities, such as gene expression, necessitating the use of stochastic models to capture its dynamics. The chemical master equation (CME) is a commonly used stochastic model of Kolmogorov forward equations that describe how the probability distribution of a chemically reacting system varies with time. Finding analytic solutions to the CME can have benefits, such as expediting simulations of multiscale biochemical reaction networks and aiding the design of distributional responses. However, analytic solutions are rarely known. A recent method of computing analytic stationary solutions relies on gluing simple state spaces together recursively at one or two states. We explore the capabilities of this method and introduce algorithms to derive analytic stationary solutions to the CME. We first formally characterize state spaces that can be constructed by performing single-state gluing of paths, cycles or both sequentially. We then study stochastic biochemical reaction networks that consist of reversible, elementary reactions with two-dimensional state spaces. We also discuss extending the method to infinite state spaces and designing the stationary behaviour of stochastic biochemical reaction networks. Finally, we illustrate the aforementioned ideas using examples that include two interconnected transcriptional components and biochemical reactions with two-dimensional state spaces.
| S-EPMC5454304 | biostudies-literature
Project description:Many chemical reaction networks in biological systems present complex oscillatory dynamics. In systems such as regulatory gene networks, cell cycle, and enzymatic processes, the number of molecules involved is often far from the thermodynamic limit. Although stochastic models based on the probabilistic approach of the Chemical Master Equation (CME) have been proposed, studies in the literature have been limited by the challenges of solving the CME and the lack of computational power to perform large-scale stochastic simulations. In this paper, we show that the infinite set of stationary moment equations describing the stochastic Brusselator and Schnakenberg oscillatory reactions networks can be truncated and solved using maximization of the entropy of the distributions. The results from our numerical experiments compare with the distributions obtained from well-established kinetic Monte Carlo methods and suggest that the accuracy of the prediction increases exponentially with the closure order chosen for the system. We conclude that maximum entropy models can be used as an efficient closure scheme alternative for moment equations to predict the non-equilibrium stationary distributions of stochastic chemical reactions with oscillatory dynamics. This prediction is accomplished without any prior knowledge of the system dynamics and without imposing any biased assumptions on the mathematical relations among species involved.
| S-EPMC6424531 | biostudies-literature
Project description:Nature presents multiple intriguing examples of processes that proceed with high precision and regularity. This remarkable stability is frequently counter to modellers' experience with the inherent stochasticity of chemical reactions in the regime of low-copy numbers. Moreover, the effects of noise and nonlinearities can lead to 'counterintuitive' behaviour, as demonstrated for a basic enzymatic reaction scheme that can display stochastic focusing (SF). Under the assumption of rapid signal fluctuations, SF has been shown to convert a graded response into a threshold mechanism, thus attenuating the detrimental effects of signal noise. However, when the rapid fluctuation assumption is violated, this gain in sensitivity is generally obtained at the cost of very large product variance, and this unpredictable behaviour may be one possible explanation of why, more than a decade after its introduction, SF has still not been observed in real biochemical systems. In this work, we explore the noise properties of a simple enzymatic reaction mechanism with a small and fluctuating number of active enzymes that behaves as a high-gain, noisy amplifier due to SF caused by slow enzyme fluctuations. We then show that the inclusion of a plausible negative feedback mechanism turns the system from a noisy signal detector to a strong homeostatic mechanism by exchanging high gain with strong attenuation in output noise and robustness to parameter variations. Moreover, we observe that the discrepancy between deterministic and stochastic descriptions of stochastically focused systems in the evolution of the means almost completely disappears, despite very low molecule counts and the additional nonlinearity due to feedback. The reaction mechanism considered here can provide a possible resolution to the apparent conflict between intrinsic noise and high precision in critical intracellular processes.
| S-EPMC4707857 | biostudies-literature
Project description:To deal with the growing scale of molecular systems, sophisticated modelling techniques have been designed in recent years to reduce the complexity of mathematical models. Among them, a widely used approach is delayed reaction for simplifying multistep reactions. However, recent research results suggest that a delayed reaction with constant time delay is unable to describe multistep reactions accurately. To address this issue, we propose a novel approach using state-dependent time delay to approximate multistep reactions. We first use stochastic simulations to calculate time delay arising from multistep reactions exactly. Then we design algorithms to calculate time delay based on system dynamics precisely. To demonstrate the power of proposed method, two processes of mRNA degradation are used to investigate the function of time delay in determining system dynamics. In addition, a multistep pathway of metabolic synthesis is used to explore the potential of the proposed method to simplify multistep reactions with nonlinear reaction rates. Simulation results suggest that the state-dependent time delay is a promising and accurate approach to reduce model complexity and decrease the number of unknown parameters in the models.
| S-EPMC4995396 | biostudies-literature
Project description:Many biochemical reaction networks are inherently multiscale in time and in the counts of participating molecular species. A standard technique to treat different time scales in the stochastic kinetics framework is averaging or quasi-steady-state analysis: it is assumed that the fast dynamics reaches its equilibrium (stationary) distribution on a time scale where the slowly varying molecular counts are unlikely to have changed. We derive analytic equilibrium distributions for various simple biochemical systems, such as enzymatic reactions and gene regulation models. These can be directly inserted into simulations of the slow time-scale dynamics. They also provide insight into the stimulus-response of these systems. An important model for which we derive the analytic equilibrium distribution is the binding of dimer transcription factors (TFs) that first have to form from monomers. This gene regulation mechanism is compared to the cases of the binding of simple monomer TFs to one gene or to multiple copies of a gene, and to the cases of the cooperative binding of two or multiple TFs to a gene. The results apply equally to ligands binding to enzyme molecules.
| S-EPMC4208355 | biostudies-literature
Project description:Quantiles are available in various problems for developing probability distributions. In some problems quantiles are elicited from experts and used for fitting parametric models, which induce non-elicited information. In some other problems comparisons are made with a quantile of an assumed model which is noncommittal to the quantile information. The maximum entropy (ME) principle provides models that avoid these issues. However, the information theory literature has been mainly concerned about models based on moment information. This paper explores the ME models that are the minimum elaborations of the uniform and moment-based ME models by quantiles. This property provides diagnostics for the utility of elaboration in terms of the information value of each type of information over the other. The ME model with quantiles and moments is represented as the mixture of truncated distributions on consecutive intervals whose shapes and existence are determined by the moments. Elaborations of several ME distributions by quantiles are presented. The ME model based only on quantiles elicited by the fixed interval method possesses a useful property for pooling information elicited from multiple experts. The elaboration of Laplace distribution is an extension of the information theory connection with minimum risk under symmetric loss functions to the asymmetric linear loss. This extension produces a new Asymmetric Laplace distribution. Application examples compare ME priors with a parametric model fitted to elicited quantiles, illustrate measuring uncertainty and disagreement of economic forecasters based on elicited probabilities, and adjust ME models for a fundamental quantile in an inventory management problem.
| S-EPMC7414396 | biostudies-literature
Project description:Gene expression is significantly stochastic making modeling of genetic networks challenging. We present an approximation that allows the calculation of not only the mean and variance, but also the distribution of protein numbers. We assume that proteins decay substantially more slowly than their mRNA and confirm that many genes satisfy this relation by using high-throughput data from budding yeast. For a two-stage model of gene expression, with transcription and translation as first-order reactions, we calculate the protein distribution for all times greater than several mRNA lifetimes and thus qualitatively predict the distribution of times for protein levels to first cross an arbitrary threshold. If in addition the fluctuates between inactive and active states, we can find the steady-state protein distribution, which can be bimodal if fluctuations of the promoter are slow. We show that our assumptions imply that protein synthesis occurs in geometrically distributed bursts and allows mRNA to be eliminated from a master equation description. In general, we find that protein distributions are asymmetric and may be poorly characterized by their mean and variance. Through maximum likelihood methods, our expressions should therefore allow more quantitative comparisons with experimental data. More generally, we introduce a technique to derive a simpler, effective dynamics for a stochastic system by eliminating a fast variable.
| S-EPMC2582303 | biostudies-literature
Project description:Probability distributions having power-law tails are observed in a broad range of social, economic, and biological systems. We describe here a potentially useful common framework. We derive distribution functions for situations in which a "joiner particle" k pays some form of price to enter a community of size , where costs are subject to economies of scale. Maximizing the Boltzmann-Gibbs-Shannon entropy subject to this energy-like constraint predicts a distribution having a power-law tail; it reduces to the Boltzmann distribution in the absence of economies of scale. We show that the predicted function gives excellent fits to 13 different distribution functions, ranging from friendship links in social networks, to protein-protein interactions, to the severity of terrorist attacks. This approach may give useful insights into when to expect power-law distributions in the natural and social sciences.
| S-EPMC3870711 | biostudies-literature