Detecting responsible nodes in differential Bayesian networks.

To study the roles that different nodes play in differentiating Bayesian networks under two states, such as control versus disease, we formulate two node-specific scores to facilitate such assessment. The first score is motivated by the prediction invariance property of a causal model. The second score results from modifying an existing score constructed for differential analysis of undirected networks. We develop strategies based on these scores to identify nodes responsible for topological differences between two Bayesian networks. Synthetic data and real-life data from designed experiments are used to demonstrate the efficacy of the proposed methods in detecting responsible nodes.

Parametric modal regression with error in covariates.

An inference procedure is proposed to provide consistent estimators of parameters in a modal regression model with a covariate prone to measurement error. A score-based diagnostic tool exploiting parametric bootstrap is developed to assess adequacy of parametric assumptions imposed on the regression model. The proposed estimation method and diagnostic tool are applied to synthetic data generated from simulation experiments and data from real-world applications to demonstrate their implementation and performance. These empirical examples illustrate the importance of adequately accounting for measurement error in the error-prone covariate when inferring the association between a response and covariates based on a modal regression model that is especially suitable for skewed and heavy-tailed response data.

Corrected score methods for estimating Bayesian networks with error-prone nodes.

Motivated by inferring cellular signaling networks using noisy flow cytometry data, we develop procedures to draw inference for Bayesian networks based on error-prone data. Two methods for inferring causal relationships between nodes in a network are proposed based on penalized estimation methods that account for measurement error and encourage sparsity. We discuss consistency of the proposed network estimators and develop an approach for selecting the tuning parameter in the penalized estimation methods. Empirical studies are carried out to compare the proposed methods with a naive method that ignores measurement error. Finally, we apply these methods to infer signaling networks using single cell flow cytometry data.

Gaussian Bayesian network comparisons with graph ordering unknown.

A Bayesian approach is proposed that unifies Gaussian Bayesian network constructions and comparisons between two networks (identical or differential) for data with graph ordering unknown. When sampling graph ordering, to escape from local maximums, an adjusted single queue equi-energy algorithm is applied. The conditional posterior probability mass function for network differentiation is derived and its asymptotic proposition is theoretically assessed. Simulations are used to demonstrate the approach and compare with existing methods. Based on epigenetic data at a set of DNA methylation sites (CpG sites), the proposed approach is further examined on its ability to detect network differentiations. Findings from theoretical assessment, simulations, and real data applications support the efficacy and efficiency of the proposed method for network comparisons.

Parametric mode regression for bounded responses.

We propose new parametric frameworks of regression analysis with the conditional mode of a bounded response as the focal point of interest. Covariate effects estimation and prediction based on the maximum likelihood method under two new classes of regression models are demonstrated. We also develop graphical and numerical diagnostic tools to detect various sources of model misspecification. Predictions based on different central tendency measures inferred using various regression models are compared using synthetic data in simulations. Finally, we conduct regression analysis for data from the Alzheimer's Disease Neuroimaging Initiative to demonstrate practical implementation of the proposed methods. Supporting Information that contain technical details and additional simulation and data analysis results are available online.

Local polynomial regression for pooled response data.

We propose local polynomial estimators for the conditional mean of a continuous response when only pooled response data are collected under different pooling designs. Asymptotic properties of these estimators are investigated and compared. Extensive simulation studies are carried out to compare finite sample performance of the proposed estimators under various model settings and pooling strategies. We apply the proposed local polynomial regression methods to two real-life applications to illustrate practical implementation and performance of the estimators for the mean function.

Size and Shape Analysis of Error-Prone Shape Data.

We consider the problem of comparing sizes and shapes of objects when landmark data are prone to measurement error. We show that naive implementation of ordinary Procrustes analysis that ignores measurement error can compromise inference. To account for measurement error, we propose the conditional score method for matching configurations, which guarantees consistent inference under mild model assumptions. The effects of measurement error on inference from naive Procrustes analysis and the performance of the proposed method are illustrated via simulation and application in three real data examples. Supplementary materials for this article are available online.

An improved test of latent-variable model misspecification in structural measurement error models for group testing data.

We consider structural measurement error models for group testing data. Likelihood inference based on structural measurement error models requires one to specify a model for the latent true predictors. Inappropriate specification of this model can lead to erroneous inference. We propose a new method tailored to detect latent-variable model misspecification in structural measurement error models for group testing data. Compared with the existing diagnostic methods developed for the same purpose, our method shows vast improvement in the power to detect latent-variable model misspecification in group testing design. We illustrate the implementation and performance of the proposed method via simulation and application to a real data example.

Latent-model robustness in joint models for a primary endpoint and a longitudinal process.

Joint modeling of a primary response and a longitudinal process via shared random effects is widely used in many areas of application. Likelihood-based inference on joint models requires model specification of the random effects. Inappropriate model specification of random effects can compromise inference. We present methods to diagnose random effect model misspecification of the type that leads to biased inference on joint models. The methods are illustrated via application to simulated data, and by application to data from a study of bone mineral density in perimenopausal women and data from an HIV clinical trial.

On latent-variable model misspecification in structural measurement error models for binary response.

We consider structural measurement error models for a binary response. We show that likelihood-based estimators obtained from fitting structural measurement error models with pooled binary responses can be far more robust to covariate measurement error in the presence of latent-variable model misspecification than the corresponding estimators from individual responses. Furthermore, despite the loss in information, pooling can provide improved parameter estimators in terms of mean-squared error. Based on these and other findings, we create a new diagnostic method to detect latent-variable model misspecification in structural measurement error models with individual binary response. We use simulation and data from the Framingham Heart Study to illustrate our methods.

Diagnosis of random-effect model misspecification in generalized linear mixed models for binary response.

SUMMARY: Generalized linear mixed models (GLMMs) are widely used in the analysis of clustered data. However, the validity of likelihood-based inference in such analyses can be greatly affected by the assumed model for the random effects. We propose a diagnostic method for random-effect model misspecification in GLMMs for clustered binary response. We provide a theoretical justification of the proposed method and investigate its finite sample performance via simulation. The proposed method is applied to data from a longitudinal respiratory infection study.