Functional analysis of high-content high-throughput imaging data

High-content automated imaging platforms allow the multiplexing of several targets simultaneously to generate multi-parametric single-cell data sets over extended periods of time. Typically, standard simple measures such as mean value of all cells at every time point are calculated to summarize the temporal process, resulting in loss of time dynamics of the single cells. Multiple experiments are performed but observation time points are not necessarily identical, leading to difficulties when integrating summary measures from different experiments. We used functional data analysis to analyze continuous curve data, where the temporal process of a response variable for each single cell can be described using a smooth curve. This allows analyses to be performed on continuous functions, rather than on original discrete data points. Functional regression models were applied to determine common temporal characteristics of a set of single cell curves and random effects were employed in the models to explain variation between experiments. The aim of the multiplexing approach is to simultaneously analyze the effect of a large number of compounds in comparison to control to discriminate between their mode of action. Functional principal component analysis based on T-statistic curves for pairwise comparison to control was used to study time-dependent compound effects.     

A new log-location regression model: estimation,influence diagnostics and residual analysis

We introduce a log-linear regression model based on the odd log-logistic generalized half-normal distribution [7 G.M. Cordeiro, M. Alizadeh, R.R. Pescim, and E.M.M. Ortega, The odd log-logistic generalized half-normal lifetime distribution: Properties and applications, Comm. Statist. Theory Methods (2015), accepted for publication. [Google Scholar]]. Some of its structural properties including explicit expressions for the density function, quantile and generating functions and ordinary moments are derived. We estimate the model parameters by the maximum likelihood method. For different parameter settings, proportion of censoring and sample size, some simulations are performed to investigate the behavior of the estimators. We derive the appropriate matrices for assessing local influence diagnostics on the parameter estimates under different perturbation schemes. We also define the martingale and modified deviance residuals to detect outliers and evaluate the model assumptions. In addition, we demonstrate that the extended regression model can be very useful in the analysis of real data and provide more realistic fits than other special regression models. The potentiality of the new regression model is illustrated by means of a real data set.     

Score test for homogeneity of dispersion in generalized Poisson mixed models with excess zeros

In many applications, the clustered count data often contain excess zeros and the zero-inflated generalized Poisson mixed (ZIGPM) regression model may be suitable. However, dispersion in ZIGPM is often treated as fixed unknown parameter, and this assumption may be not appropriate in some situations. In this article, a score test for homogeneity of dispersion parameter in ZIGPM regression model is developed and corresponding test statistic is obtained. Sampling distribution and power of the score test statistic are investigated through Monte Carlo simulation. Finally, results from a biological example illustrate the usefulness of the diagnostic statistic.     

Empirical Uncertain Bayes Methods in Area‐level Models

Random effects model can account for the lack of fitting a regression model and increase precision of estimating area‐level means. However, in case that the synthetic mean provides accurate estimates, the prior distribution may inflate an estimation error. Thus, it is desirable to consider the uncertain prior distribution, which is expressed as the mixture of a one‐point distribution and a proper prior distribution. In this paper, we develop an empirical Bayes approach for estimating area‐level means, using the uncertain prior distribution in the context of a natural exponential family, which we call the empirical uncertain Bayes (EUB) method. The regression model considered in this paper includes the Poisson‐gamma and the binomial‐beta, and the normal‐normal (Fay–Herriot) model, which are typically used in small area estimation. We obtain the estimators of hyperparameters based on the marginal likelihood by using a well‐known expectation‐maximization algorithm and propose the EUB estimators of area means. For risk evaluation of the EUB estimator, we derive a second‐order unbiased estimator of a conditional mean squared error by using some techniques of numerical calculation. Through simulation studies and real data applications, we evaluate a performance of the EUB estimator and compare it with the usual empirical Bayes estimator.     

Tests for Structural Changes in Time Series of Counts

We propose methods for detecting structural changes in time series with discrete‐valued observations. The detector statistics come in familiar L2‐type formulations incorporating the empirical probability generating function. Special emphasis is given to the popular models of integer autoregression and Poisson autoregression. For both models, we study mainly structural changes due to a change in distribution, but we also comment for the classical problem of parameter change. The asymptotic properties of the proposed test statistics are studied under the null hypothesis as well as under alternatives. A Monte Carlo power study on bootstrap versions of the new methods is also included along with a real data example.     

Robust modal estimation and variable selection for single-index varying-coefficient models

In this article, we present a new efficient iteration estimation approach based on local modal regression for single-index varying-coefficient models. The resulted estimators are shown to be robust with regardless of outliers and error distributions. The asymptotic properties of the estimators are established under some regularity conditions and a practical modified EM algorithm is proposed for the new method. Moreover, to achieve sparse estimator when there exists irrelevant variables in the index parameters, a variable selection procedure based on SCAD penalty is developed to select significant parametric covariates and the well-known oracle properties are also derived. Finally, some numerical examples with various distributed errors and a real data analysis are conducted to illustrate the validity and feasibility of our proposed method.