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Anindya Bhadra, Arvind Rao, Veerabhadran Baladandayuthapani
Inferring dependence structure through undirected graphs is crucial for uncovering the major modes of multivariate interaction among high-dimensional genomic markers that are potentially associated with cancer. Traditionally, conditional independence has been studied using sparse Gaussian graphical models for continuous data and sparse Ising models for discrete data. However, there are two clear situations when these approaches are inadequate. The first occurs when the data are continuous but display non-normal marginal behavior such as heavy tails or skewness, rendering an assumption of normality inappropriate...
April 24, 2017: Biometrics
Hao Liu, Jing Qin
Multivariate current-status data are frequently encountered in biomedical and public health studies. Semiparametric regression models have been extensively studied for univariate current-status data, but most existing estimation procedures are computationally intensive, involving either penalization or smoothing techniques. It becomes more challenging for the analysis of multivariate current-status data. In this article, we study the maximum likelihood estimations for univariate and bivariate current-status data under the semiparametric probit regression models...
April 24, 2017: Biometrics
Donald Hedeker, Stephen H C du Toit, Hakan Demirtas, Robert D Gibbons
This article discusses marginalization of the regression parameters in mixed models for correlated binary outcomes. As is well known, the regression parameters in such models have the "subject-specific" (SS) or conditional interpretation, in contrast to the "population-averaged" (PA) or marginal estimates that represent the unconditional covariate effects. We describe an approach using numerical quadrature to obtain PA estimates from their SS counterparts in models with multiple random effects. Standard errors for the PA estimates are derived using the delta method...
April 20, 2017: Biometrics
Gen Li, Sungkyu Jung
In modern biomedical research, it is ubiquitous to have multiple data sets measured on the same set of samples from different views (i.e., multi-view data). For example, in genetic studies, multiple genomic data sets at different molecular levels or from different cell types are measured for a common set of individuals to investigate genetic regulation. Integration and reduction of multi-view data have the potential to leverage information in different data sets, and to reduce the magnitude and complexity of data for further statistical analysis and interpretation...
April 13, 2017: Biometrics
Denis Agniel, Tianxi Cai
Studying multiple outcomes simultaneously allows researchers to begin to identify underlying factors that affect all of a set of diseases (i.e., shared etiology) and what may give rise to differences in disorders between patients (i.e., disease subtypes). In this work, our goal is to build risk scores that are predictive of multiple phenotypes simultaneously and identify subpopulations at high risk of multiple phenotypes. Such analyses could yield insight into etiology or point to treatment and prevention strategies...
April 13, 2017: Biometrics
Yongqiang Tang
Control-based pattern mixture models (PMM) and delta-adjusted PMMs are commonly used as sensitivity analyses in clinical trials with non-ignorable dropout. These PMMs assume that the statistical behavior of outcomes varies by pattern in the experimental arm in the imputation procedure, but the imputed data are typically analyzed by a standard method such as the primary analysis model. In the multiple imputation (MI) inference, Rubin's variance estimator is generally biased when the imputation and analysis models are uncongenial...
April 13, 2017: Biometrics
Philip T Reiss, Lei Huang, Pei-Shien Wu, Huaihou Chen, Stan Colcombe
We extend the notion of an influence or hat matrix to regression with functional responses and scalar predictors. For responses depending linearly on a set of predictors, our definition is shown to reduce to the conventional influence matrix for linear models. The pointwise degrees of freedom, the trace of the pointwise influence matrix, are shown to have an adaptivity property that motivates a two-step bivariate smoother for modeling nonlinear dependence on a single predictor. This procedure adapts to varying complexity of the nonlinear model at different locations along the function, and thereby achieves better performance than competing tensor product smoothers in an analysis of the development of white matter microstructure in the brain...
April 12, 2017: Biometrics
Christopher S McMahan, Joshua M Tebbs, Timothy E Hanson, Christopher R Bilder
Group testing involves pooling individual specimens (e.g., blood, urine, swabs, etc.) and testing the pools for the presence of a disease. When individual covariate information is available (e.g., age, gender, number of sexual partners, etc.), a common goal is to relate an individual's true disease status to the covariates in a regression model. Estimating this relationship is a nonstandard problem in group testing because true individual statuses are not observed and all testing responses (on pools and on individuals) are subject to misclassification arising from assay error...
April 12, 2017: Biometrics
Jingjing Yang, Dennis D Cox, Jong Soo Lee, Peng Ren, Taeryon Choi
Functional data are defined as realizations of random functions (mostly smooth functions) varying over a continuum, which are usually collected on discretized grids with measurement errors. In order to accurately smooth noisy functional observations and deal with the issue of high-dimensional observation grids, we propose a novel Bayesian method based on the Bayesian hierarchical model with a Gaussian-Wishart process prior and basis function representations. We first derive an induced model for the basis-function coefficients of the functional data, and then use this model to conduct posterior inference through Markov chain Monte Carlo methods...
April 10, 2017: Biometrics
Kyu Ha Lee, Virginie Rondeau, Sebastien Haneuse
Statistical analyses that investigate risk factors for Alzheimer's disease (AD) are often subject to a number of challenges. Some of these challenges arise due to practical considerations regarding data collection such that the observation of AD events is subject to complex censoring including left-truncation and either interval or right-censoring. Additional challenges arise due to the fact that study participants under investigation are often subject to competing forces, most notably death, that may not be independent of AD...
April 10, 2017: Biometrics
Vanda InĂ¡cio de Carvalho, Miguel de Carvalho, Adam J Branscum
A novel nonparametric regression model is developed for evaluating the covariate-specific accuracy of a continuous biological marker. Accurately screening diseased from nondiseased individuals and correctly diagnosing disease stage are critically important to health care on several fronts, including guiding recommendations about combinations of treatments and their intensities. The accuracy of a continuous medical test or biomarker varies by the cutoff threshold (c) used to infer disease status. Accuracy can be measured by the probability of testing positive for diseased individuals (the true positive probability or sensitivity, Se(c), of the test), and the true negative probability (specificity, Sp(c)) of the test...
April 4, 2017: Biometrics
Huiming Lin, Bo Fu, Guoyou Qin, Zhongyi Zhu
We develop a doubly robust estimation of generalized partial linear models for longitudinal data with dropouts. Our method extends the highly efficient aggregate unbiased estimating function approach proposed in Qu et al. (2010) to a doubly robust one in the sense that under missing at random (MAR), our estimator is consistent when either the linear conditional mean condition is satisfied or a model for the dropout process is correctly specified. We begin with a generalized linear model for the marginal mean, and then move forward to a generalized partial linear model, allowing for nonparametric covariate effect by using the regression spline smoothing approximation...
April 3, 2017: Biometrics
Jinyuan Chang, Chao Zheng, Wen-Xin Zhou, Wen Zhou
In this article, we study the problem of testing the mean vectors of high dimensional data in both one-sample and two-sample cases. The proposed testing procedures employ maximum-type statistics and the parametric bootstrap techniques to compute the critical values. Different from the existing tests that heavily rely on the structural conditions on the unknown covariance matrices, the proposed tests allow general covariance structures of the data and therefore enjoy wide scope of applicability in practice. To enhance powers of the tests against sparse alternatives, we further propose two-step procedures with a preliminary feature screening step...
March 31, 2017: Biometrics
Pixu Shi, Hongzhe Li
In human microbiome studies, sequencing reads data are often summarized as counts of bacterial taxa at various taxonomic levels specified by a taxonomic tree. This article considers the problem of analyzing two repeated measurements of microbiome data from the same subjects. Such data are often collected to assess the change of microbial composition after certain treatment, or the difference in microbial compositions across body sites. Existing models for such count data are limited in modeling the covariance structure of the counts and in handling paired multinomial count data...
March 30, 2017: Biometrics
Yunlong Nie, LiangLiang Wang, Jiguo Cao
The problem of modeling the dynamical regulation process within a gene network has been of great interest for a long time. We propose to model this dynamical system with a large number of nonlinear ordinary differential equations (ODEs), in which the regulation function is estimated directly from data without any parametric assumption. Most current research assumes the gene regulation network is static, but in reality, the connection and regulation function of the network may change with time or environment...
March 29, 2017: Biometrics
Chong Deng, Yongtao Guan, Rasmus P Waagepetersen, Jingfei Zhang
Applications of spatial point processes for large and complex data sets with inhomogeneities as encountered, example, in tropical rain forest ecology call for estimation methods that are both statistically and computationally efficient. We propose a novel second-order quasi-likelihood procedure to estimate the parameters for a second-order intensity reweighted stationary spatial point process. Our approach is to derive first- and second-order estimating functions and then combine them linearly using appropriate weight functions...
March 29, 2017: Biometrics
Tamar Sofer, Elizabeth D Schifano, David C Christiani, Xihong Lin
We propose a weighted pseudolikelihood method for analyzing the association of a SNP set, example, SNPs in a gene or a genetic pathway or network, with multiple secondary phenotypes in case-control genetic association studies. To boost analysis power, we assume that the SNP-specific effects are shared across all secondary phenotypes using a scaled mean model. We estimate regression parameters using Inverse Probability Weighted (IPW) estimating equations obtained from the weighted pseudolikelihood, which accounts for case-control sampling to prevent potential ascertainment bias...
March 27, 2017: Biometrics
Pranab Ghosh, Lingyun Liu, P Senchaudhuri, Ping Gao, Cyrus Mehta
Two-arm group sequential designs have been widely used for over 40 years, especially for studies with mortality endpoints. The natural generalization of such designs to trials with multiple treatment arms and a common control (MAMS designs) has, however, been implemented rarely. While the statistical methodology for this extension is clear, the main limitation has been an efficient way to perform the computations. Past efforts were hampered by algorithms that were computationally explosive. With the increasing interest in adaptive designs, platform designs, and other innovative designs that involve multiple comparisons over multiple stages, the importance of MAMS designs is growing rapidly...
March 27, 2017: Biometrics
Raiden Hasegawa, Dylan Small
In matched observational studies where treatment assignment is not randomized, sensitivity analysis helps investigators determine how sensitive their estimated treatment effect is to some unmeasured confounder. The standard approach calibrates the sensitivity analysis according to the worst case bias in a pair. This approach will result in a conservative sensitivity analysis if the worst case bias does not hold in every pair. In this paper, we show that for binary data, the standard approach can be calibrated in terms of the average bias in a pair rather than worst case bias...
March 27, 2017: Biometrics
Steven Abrams, Marc Aerts, Geert Molenberghs, Niel Hens
Frailty models have a prominent place in survival analysis to model univariate and multivariate time-to-event data, often complicated by the presence of different types of censoring. In recent years, frailty modeling gained popularity in infectious disease epidemiology to quantify unobserved heterogeneity using Type I interval-censored serological data or current status data. In a multivariate setting, frailty models prove useful to assess the association between infection times related to multiple distinct infections acquired by the same individual...
March 27, 2017: Biometrics
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