Biometrics最新文献

The increasing availability of high-dimensional, longitudinal measures of gene expression can facilitate understanding of biological mechanisms, as required for precision medicine. Biological knowledge suggests that it may be best to describe complex diseases at the level of underlying pathways, which may interact with one another. We propose a Bayesian approach that allows for characterizing such correlation among different pathways through dependent Gaussian processes (DGP) and mapping the observed high-dimensional gene expression trajectories into unobserved low-dimensional pathway expression trajectories via Bayesian sparse factor analysis. Our proposal is the first attempt to relax the classical assumption of independent factors for longitudinal data and has demonstrated a superior performance in recovering the shape of pathway expression trajectories, revealing the relationships between genes and pathways, and predicting gene expressions (closer point estimates and narrower predictive intervals), as demonstrated through simulations and real data analysis. To fit the model, we propose a Monte Carlo expectation maximization (MCEM) scheme that can be implemented conveniently by combining a standard Markov Chain Monte Carlo sampler and an R package GPFDA,which returns the maximum likelihood estimates of DGP hyperparameters. The modular structure of MCEM makes it generalizable to other complex models involving the DGP model component. Our R package DGP4LCF that implements the proposed approach is available on the Comprehensive R Archive Network (CRAN).

In this paper, we propose Varying Effects Regression with Graph Estimation (VERGE), a novel Bayesian method for feature selection in regression. Our model has key aspects that allow it to leverage the complex structure of data sets arising from genomics or imaging studies. We distinguish between the predictors, which are the features utilized in the outcome prediction model, and the subject-level covariates, which modulate the effects of the predictors on the outcome. We construct a varying coefficients modeling framework where we infer a network among the predictor variables and utilize this network information to encourage the selection of related predictors. We employ variable selection spike-and-slab priors that enable the selection of both network-linked predictor variables and covariates that modify the predictor effects. We demonstrate through simulation studies that our method outperforms existing alternative methods in terms of both feature selection and predictive accuracy. We illustrate VERGE with an application to characterizing the influence of gut microbiome features on obesity, where we identify a set of microbial taxa and their ecological dependence relations. We allow subject-level covariates, including sex and dietary intake variables to modify the coefficients of the microbiome predictors, providing additional insight into the interplay between these factors.

Mouse-tracking data, which record computer mouse trajectories while participants perform an experimental task, provide valuable insights into subjects' underlying cognitive processes. Neuroscientists are interested in clustering the subjects' responses during computer mouse-tracking tasks to reveal patterns of individual decision-making behaviors and identify population subgroups with similar neurobehavioral responses. These data can be combined with neuroimaging data to provide additional information for personalized interventions. In this article, we develop a novel hierarchical shrinkage partition (HSP) prior for clustering summary statistics derived from the trajectories of mouse-tracking data. The HSP model defines a subjects' cluster as a set of subjects that gives rise to more similar (rather than identical) nested partitions of the conditions. The proposed model can incorporate prior information about the partitioning of either subjects or conditions to facilitate clustering, and it allows for deviations of the nested partitions within each subject group. These features distinguish the HSP model from other bi-clustering methods that typically create identical nested partitions of conditions within a subject group. Furthermore, it differs from existing nested clustering methods, which define clusters based on common parameters in the sampling model and identify subject groups by different distributions. We illustrate the unique features of the HSP model on a mouse tracking dataset from a pilot study and in simulation studies. Our results show the ability and effectiveness of the proposed exploratory framework in clustering and revealing possible different behavioral patterns across subject groups.

This paper introduces a model for longitudinal functional data analysis that accounts for pointwise skewness. The proposed procedure decouples the marginal pointwise variation from the complex longitudinal and functional dependence using copula methodology. Pointwise variation is described through parametric distribution functions that capture varying skewness and change smoothly both in time and over the functional argument. Joint dependence is quantified through a Gaussian copula with a low-rank approximation-based covariance. The introduced class of models provides a unifying platform for both pointwise quantile estimation and prediction of complete trajectories at new times. We investigate the methods numerically in simulations and discuss their application to a diffusion tensor imaging study of multiple sclerosis patients. This approach is implemented in the R package sLFDA that is publicly available on GitHub.

Model averaging is an important tool for treating uncertainty from model selection process and fusing information from different models, and has been widely used in various fields. However, the most existing model averaging criteria are proposed based on the methods of ordinary least squares or maximum likelihood, which possess high sensitivity to outliers or violation of certain model assumption. For the mean regression, no optimal robust methods are developed. To fill this gap, in our paper, we propose an outlier-robust model averaging approach by Mallows-type criterion. The idea is that we first construct a generalized M (GM) estimator for each candidate model, and then build robust weighting schemes by the asymptotic expansion of the final prediction error based on the GM-type loss function. So, we can still achieve a trustworthy result even if the dataset is contaminated by outliers in response and/or covariates. Asymptotic properties of the proposed robust model averaging estimators are established under some regularity conditions. The consistency of our weight estimators tending to the theoretically optimal weight vectors is also derived. We prove that our model averaging estimator is robust in terms of having bounded influence function. Further, we define the empirical prediction influence function to evaluate the quantitative robustness of the model averaging estimator. A simulation study and a real data analysis are conducted to demonstrate the finite sample performance of our estimators and compare them with other commonly used model selection and averaging methods.

One of the goals of precision psychiatry is to characterize mental disorders in an individualized manner, taking into account the underlying dynamic processes. Recent advances in mobile technologies have enabled the collection of ecological momentary assessments that capture multiple responses in real-time at high frequency. However, ecological momentary assessment data are often multi-dimensional, correlated, and hierarchical. Mixed-effect models are commonly used but may require restrictive assumptions about the fixed and random effects and the correlation structure. The recurrent temporal restricted Boltzmann machine (RTRBM) is a generative neural network that can be used to model temporal data, but most existing RTRBM approaches do not account for the potential heterogeneity of group dynamics within a population based on available covariates. In this paper, we propose a new temporal generative model, the HDRBM, to learn the heterogeneous group dynamics and demonstrate the effectiveness of this approach on simulated and real-world ecological momentary assessment datasets. We show that by incorporating covariates, HDRBM can improve accuracy and interpretability, explore the underlying drivers of the group dynamics of participants, and serve as a generative model for ecological momentary assessment studies.

Randomized trials seek efficient treatment effect estimation within target populations, yet scientific interest often also centers on subpopulations. Although there are typically too few subjects within each subpopulation to efficiently estimate these subpopulation treatment effects, one can gain precision by borrowing strength across subpopulations, as is the case in a basket trial. While dynamic borrowing has been proposed as an efficient approach to estimating subpopulation treatment effects on primary endpoints, additional efficiency could be gained by leveraging the information found in secondary endpoints. We propose a multisource exchangeability model (MEM) that incorporates secondary endpoints to more efficiently assess subpopulation exchangeability. Across simulation studies, our proposed model almost uniformly reduces the mean squared error when compared to the standard MEM that only considers data from the primary endpoint by gaining efficiency when subpopulations respond similarly to the treatment and reducing the magnitude of bias when the subpopulations are heterogeneous. We illustrate our model's feasibility using data from a recently completed trial of very low nicotine content cigarettes to estimate the effect on abstinence from smoking within three priority subpopulations. Our proposed model led to increases in the effective sample size two to four times greater than under the standard MEM.

Recent breakthroughs in spatially resolved transcriptomics (SRT) technologies have enabled comprehensive molecular characterization at the spot or cellular level while preserving spatial information. Cells are the fundamental building blocks of tissues, organized into distinct yet connected components. Although many non-spatial and spatial clustering approaches have been used to partition the entire region into mutually exclusive spatial domains based on the SRT high-dimensional molecular profile, most require an ad hoc selection of less interpretable dimensional-reduction techniques. To overcome this challenge, we propose a zero-inflated negative binomial mixture model to cluster spots or cells based on their molecular profiles. To increase interpretability, we employ a feature selection mechanism to provide a low-dimensional summary of the SRT molecular profile in terms of discriminating genes that shed light on the clustering result. We further incorporate the SRT geospatial profile via a Markov random field prior. We demonstrate how this joint modeling strategy improves clustering accuracy, compared with alternative state-of-the-art approaches, through simulation studies and 3 real data applications.

The scope of this paper is a multivariate setting involving categorical variables. Following an external manipulation of one variable, the goal is to evaluate the causal effect on an outcome of interest. A typical scenario involves a system of variables representing lifestyle, physical and mental features, symptoms, and risk factors, with the outcome being the presence or absence of a disease. These variables are interconnected in complex ways, allowing the effect of an intervention to propagate through multiple paths. A distinctive feature of our approach is the estimation of causal effects while accounting for uncertainty in both the dependence structure, which we represent through a directed acyclic graph (DAG), and the DAG-model parameters. Specifically, we propose a Markov chain Monte Carlo algorithm that targets the joint posterior over DAGs and parameters, based on an efficient reversible-jump proposal scheme. We validate our method through extensive simulation studies and demonstrate that it outperforms current state-of-the-art procedures in terms of estimation accuracy. Finally, we apply our methodology to analyze a dataset on depression and anxiety in undergraduate students.

Electronic health records and other sources of observational data are increasingly used for drawing causal inferences. The estimation of a causal effect using these data not meant for research purposes is subject to confounding and irregularly-spaced covariate-driven observation times affecting the inference. A doubly-weighted estimator accounting for these features has previously been proposed that relies on the correct specification of two nuisance models used for the weights. In this work, we propose a novel consistent multiply robust estimator and demonstrate analytically and in comprehensive simulation studies that it is more flexible and more efficient than the only alternative estimator proposed for the same setting. It is further applied to data from the Add Health study in the United States to estimate the causal effect of therapy counseling on alcohol consumption in American adolescents.