Bayesian inference for a discretely observed stochastic kinetic model

The ability to infer parameters of gene regulatory networks is emerging as a key problem in systems biology. The biochemical data are intrinsically stochastic and tend to be observed by means of discrete-time sampling systems, which are often limited in their completeness. In this paper we explore how to make Bayesian inference for the kinetic rate constants of regulatory networks, using the stochastic kinetic Lotka-Volterra system as a model. This simple model describes behaviour typical of many biochemical networks which exhibit auto-regulatory behaviour. Various MCMC algorithms are described and their performance evaluated in several data-poor scenarios. An algorithm based on an approximating process is shown to be particularly efficient.     

Shrinkage confidence intervals for the normal mean: Using a guess for greater efficiency

If the unknown mean of a univariate population is sufficiently close to the value of an initial guess then an appropriate shrinkage estimator has smaller average squared error than the sample mean. This principle has been known for some time, but it does not appear to have found extension to problems of interval estimation. The author presents valid two‐sided 95% and 99% “shrinkage” confidence intervals for the mean of a normal distribution. These intervals are narrower than the usual interval based on the Student distribution when the population mean lies in such an “effective interval.” A reduction of 20% in the mean width of the interval is possible when the population mean is sufficiently close to the value of the guess. The author also describes a modification to existing shrinkage point estimators of the general univariate mean that enables the effective interval to be enlarged.     

On an adaptive version of the Metropolis–Hastings algorithm with independent proposal distribution

In this paper, we present a general formulation of an algorithm, the adaptive independent chain (AIC), that was introduced in a special context in Gåsemyr et al . [ Methodol. Comput. Appl. Probab. 3 (2001)]. The algorithm aims at producing samples from a specific target distribution Π, and is an adaptive, non-Markovian version of the Metropolis–Hastings independent chain. A certain parametric class of possible proposal distributions is fixed, and the parameters of the proposal distribution are updated periodically on the basis of the recent history of the chain, thereby obtaining proposals that get ever closer to Π. We show that under certain conditions, the algorithm produces an exact sample from Π in a finite number of iterations, and hence that it converges to Π. We also present another adaptive algorithm, the componentwise adaptive independent chain (CAIC), which may be an alternative in particular in high dimensions. The CAIC may be regarded as an adaptive approximation to the Gibbs sampler updating parametric approximations to the conditionals of Π.     

Estimation of global temperature fields from scattered observations by a spherical-wavelet-based spatially adaptive method

Summary.  The paper considers the problem of estimating the entire temperature field for every location on the globe from scattered surface air temperatures observed by a network of weather-stations. Classical methods such as spherical harmonics and spherical smoothing splines are not efficient in representing data that have inherent multiscale structures. The paper presents an estimation method that can adapt to the multiscale characteristics of the data. The method is based on a spherical wavelet approach that has recently been developed for a multiscale representation and analysis of scattered data. Spatially adaptive estimators are obtained by coupling the spherical wavelets with different thresholding (selective reconstruction) techniques. These estimators are compared for their spatial adaptability and extrapolation performance by using the surface air temperature data.     

Modeling for Risk Assessment of Neurotoxic Effects

The regulation of noncancer toxicants, including neurotoxicants, has usually been based upon a reference dose (allowable daily intake). A reference dose is obtained by dividing a no-observed-effect level by uncertainty (safety) factors to account for intraspecies and interspecies sensitivities to a chemical. It is assumed that the risk at the reference dose is negligible, but no attempt generally is made to estimate the risk at the reference dose. A procedure is outlined that provides estimates of risk as a function of dose. The first step is to establish a mathematical relationship between a biological effect and the dose of a chemical. Knowledge of biological mechanisms and/or pharmacokinetics can assist in the choice of plausible mathematical models. The mathematical model provides estimates of average responses as a function of dose. Secondly, estimates of risk require selection of a distribution of individual responses about the average response given by the mathematical model. In the case of a normal or lognormal distribution, only an estimate of the standard deviation is needed. The third step is to define an adverse level for a response so that the probability (risk) of exceeding that level can be estimated as a function of dose. Because a firm response level often cannot be established at which adverse biological effects occur, it may be necessary to at least establish an abnormal response level that only a small proportion of individuals would exceed in an unexposed group. That is, if a normal range of responses can be established, then the probability (risk) of abnormal responses can be estimated. In order to illustrate this process, measures of the neurotransmitter serotonin and its metabolite 5-hydroxyindoleacetic acid in specific areas of the brain of rats and monkeys are analyzed after exposure to the neurotoxicant methylene-dioxymethamphetamine. These risk estimates are compared with risk estimates from the quantal approach in which animals are classified as either abnormal or not depending upon abnormal serotonin levels.     

Improved Monte Carlo inference for models with additive error

Some statistical models defined in terms of a generating stochastic mechanism have intractable distribution theory, which renders parameter estimation difficult. However, a Monte Carlo estimate of the log-likelihood surface for such a model can be obtained via computation of nonparametric density estimates from simulated realizations of the model. Unfortunately, the bias inherent in density estimation can cause bias in the resulting log-likelihood estimate that alters the location of its maximizer. In this paper a methodology for radically reducing this bias is developed for models with an additive error component. An illustrative example involving a stochastic model of molecular fragmentation and measurement is given.     

Confidence Intervals for Current Status Data

Abstract.  The likelihood ratio statistic for testing pointwise hypotheses about the survival time distribution in the current status model can be inverted to yield confidence intervals (CIs). One advantage of this procedure is that CIs can be formed without estimating the unknown parameters that figure in the asymptotic distribution of the maximum likelihood estimator (MLE) of the distribution function. We discuss the likelihood ratio-based CIs for the distribution function and the quantile function and compare these intervals to several different intervals based on the MLE. The quantiles of the limiting distribution of the MLE are estimated using various methods including parametric fitting, kernel smoothing and subsampling techniques. Comparisons are carried out both for simulated data and on a data set involving time to immunization against rubella. The comparisons indicate that the likelihood ratio-based intervals are preferable from several perspectives.     

Approximation of density functions by orthogonal series with grouped data

Summary Letg(x) andf(x) be continuous density function on (a, b) and let {ϕ_j} be a complete orthonormal sequence of functions onL ₂(g), which is the set of squared integrable functions weighted byg on (a, b). Suppose that over (a, b). Given a grouped sample of sizen fromf(x), the paper investigates the asymptotic properties of the restricted maximum likelihood estimator of density, obtained by setting all but the firstm of the ϑ_j’s equal to0. Practical suggestions are given for performing estimation via the use of Fourier and Legendre polynomial series. Research partially supported by: CNR grant, n. 93. 00837. CT10.     

A simple,automatic and adaptive bivariate density estimator based on conditional densities

The standard approach to non-parametric bivariate density estimation is to use a kernel density estimator. Practical performance of this estimator is hindered by the fact that the estimator is not adaptive (in the sense that the level of smoothing is not sensitive to local properties of the density). In this paper a simple, automatic and adaptive bivariate density estimator is proposed based on the estimation of marginal and conditional densities. Asymptotic properties of the estimator are examined, and guidance to practical application of the method is given. Application to two examples illustrates the usefulness of the estimator as an exploratory tool, particularly in situations where the local behaviour of the density varies widely. The proposed estimator is also appropriate for use as a pilot estimate for an adaptive kernel estimate, since it is relatively inexpensive to calculate.     

多元正态分布广义方差区间估计的改进

讨论了多元正态分布广义方差的区间估计问题,给出了在覆盖率及长度上均优于最优仿射同变区间估计的改进估计．