Annals of Applied Statistics最新文献

Motivated by emerging applications in ecology, microbiology, and neuroscience, this paper studies high-dimensional regression with two-way structured data. To estimate the high-dimensional coefficient vector, we propose the generalized matrix decomposition regression (GMDR) to efficiently leverage auxiliary information on row and column structures. GMDR extends the principal component regression (PCR) to two-way structured data, but unlike PCR, GMDR selects the components that are most predictive of the outcome, leading to more accurate prediction. For inference on regression coefficients of individual variables, we propose the generalized matrix decomposition inference (GMDI), a general high-dimensional inferential framework for a large family of estimators that include the proposed GMDR estimator. GMDI provides more flexibility for incorporating relevant auxiliary row and column structures. As a result, GMDI does not require the true regression coefficients to be sparse, but constrains the coordinate system representing the regression coefficients according to the column structure. GMDI also allows dependent and heteroscedastic observations. We study the theoretical properties of GMDI in terms of both the type-I error rate and power and demonstrate the effectiveness of GMDR and GMDI in simulation studies and an application to human microbiome data.

Motivated by a study of United Nations voting behaviors, we introduce a regression model for a series of networks that are correlated over time. Our model is a dynamic extension of the additive and multiplicative effects network model (AMEN) of Hoff (2021). In addition to incorporating a temporal structure, the model accommodates two types of missing data thus allows the size of the network to vary over time. We demonstrate via simulations the necessity of various components of the model. We apply the model to the United Nations General Assembly voting data from 1983 to 2014 (Voeten, 2013) to answer interesting research questions regarding international voting behaviors. In addition to finding important factors that could explain the voting behaviors, the model-estimated additive effects, multiplicative effects, and their movements reveal meaningful foreign policy positions and alliances of various countries.

The Scientific Registry of Transplant Recipients (SRTR) system has become a rich resource for understanding the complex mechanisms of graft failure after kidney transplant, a crucial step for allocating organs effectively and implementing appropriate care. As transplant centers that treated patients might strongly confound graft failures, Cox models stratified by centers can eliminate their confounding effects. Also, since recipient age is a proven non-modifiable risk factor, a common practice is to fit models separately by recipient age groups. The moderate sample sizes, relative to the number of covariates, in some age groups may lead to biased maximum stratified partial likelihood estimates and unreliable confidence intervals even when samples still outnumber covariates. To draw reliable inference on a comprehensive list of risk factors measured from both donors and recipients in SRTR, we propose a de-biased lasso approach via quadratic programming for fitting stratified Cox models. We establish asymptotic properties and verify via simulations that our method produces consistent estimates and confidence intervals with nominal coverage probabilities. Accounting for nearly 100 confounders in SRTR, the de-biased method detects that the graft failure hazard nonlinearly increases with donor's age among all recipient age groups, and that organs from older donors more adversely impact the younger recipients. Our method also delineates the associations between graft failure and many risk factors such as recipients' primary diagnoses (e.g. polycystic disease, glomerular disease, and diabetes) and donor-recipient mismatches for human leukocyte antigen loci across recipient age groups. These results may inform the refinement of donor-recipient matching criteria for stakeholders.

The majority of Americans fail to achieve recommended levels of physical activity, which leads to numerous preventable health problems such as diabetes, hypertension, and heart diseases. This has generated substantial interest in monitoring human activity to gear interventions toward environmental features that may relate to higher physical activity. Wearable devices, such as wrist-worn sensors that monitor gross motor activity (actigraph units) continuously record the activity levels of a subject, producing massive amounts of high-resolution measurements. Analyzing actigraph data needs to account for spatial and temporal information on trajectories or paths traversed by subjects wearing such devices. Inferential objectives include estimating a subject's physical activity levels along a given trajectory; identifying trajectories that are more likely to produce higher levels of physical activity for a given subject; and predicting expected levels of physical activity in any proposed new trajectory for a given set of health attributes. Here, we devise a Bayesian hierarchical modeling framework for spatial-temporal actigraphy data to deliver fully model-based inference on trajectories while accounting for subject-level health attributes and spatial-temporal dependencies. We undertake a comprehensive analysis of an original dataset from the Physical Activity through Sustainable Transport Approaches in Los Angeles (PASTA-LA) study to ascertain spatial zones and trajectories exhibiting significantly higher levels of physical activity while accounting for various sources of heterogeneity.

Low-cost air pollution sensors, offering hyper-local characterization of pollutant concentrations, are becoming increasingly prevalent in environmental and public health research. However, low-cost air pollution data can be noisy, biased by environmental conditions, and usually need to be field-calibrated by collocating low-cost sensors with reference-grade instruments. We show, theoretically and empirically, that the common procedure of regression-based calibration using collocated data systematically underestimates high air pollution concentrations, which are critical to diagnose from a health perspective. Current calibration practices also often fail to utilize the spatial correlation in pollutant concentrations. We propose a novel spatial filtering approach to collocation-based calibration of low-cost networks that mitigates the underestimation issue by using an inverse regression. The inverse-regression also allows for incorporating spatial correlations by a second-stage model for the true pollutant concentrations using a conditional Gaussian Process. Our approach works with one or more collocated sites in the network and is dynamic, leveraging spatial correlation with the latest available reference data. Through extensive simulations, we demonstrate how the spatial filtering substantially improves estimation of pollutant concentrations, and measures peak concentrations with greater accuracy. We apply the methodology for calibration of a low-cost PM_2.5 network in Baltimore, Maryland, and diagnose air pollution peaks that are missed by the regression-calibration.

Mutations in the BRCA1 and BRCA2 genes are known to be highly associated with breast cancer. Identifying both shared and unique transcript expression patterns in blood samples from these groups can shed insight into if and how the disease mechanisms differ among individuals by mutation status, but this is challenging in the high-dimensional setting. A recent method, Bayesian Multi-Study Factor Analysis (BMSFA), identifies latent factors common to all studies (or equivalently, groups) and latent factors specific to individual studies. However, BMSFA does not allow for factors shared by more than one but less than all studies. This is critical in our context, as we may expect some but not all signals to be shared by BRCA1-and BRCA2-mutation carriers but not necessarily other high-risk groups. We extend BMSFA by introducing a new method, Tetris, for Bayesian combinatorial multi-study factor analysis, which identifies latent factors that any combination of studies or groups can share. We model the subsets of studies that share latent factors with an Indian Buffet Process, and offer a way to summarize uncertainty in the sharing patterns using credible balls. We test our method with an extensive range of simulations, and showcase its utility not only in dimension reduction but also in covariance estimation. When applied to transcript expression data from high-risk families grouped by mutation status, Tetris reveals the features and pathways characterizing each group and the sharing patterns among them. Finally, we further extend Tetris to discover groupings of samples when group labels are not provided, which can elucidate additional structure in these data.

Alzheimer's disease (AD) is a complex neurological disorder impairing multiple domains such as cognition and daily functions. To better understand the disease and its progression, many AD research studies collect multiple longitudinal outcomes that are strongly predictive of the onset of AD dementia. We propose a joint model based on a multivariate functional mixed model framework (referred to as MFMM-JM) that simultaneously models the multiple longitudinal outcomes and the time to dementia onset. We develop six functional forms to fully investigate the complex association between longitudinal outcomes and dementia onset. Moreover, we use the Bayesian methods for statistical inference and develop a dynamic prediction framework that provides accurate personalized predictions of disease progressions based on new subject-specific data. We apply the proposed MFMM-JM to two large ongoing AD studies: the Alzheimer's Disease Neuroimaging Initiative (ADNI) and National Alzheimer's Coordinating Center (NACC), and identify the functional forms with the best predictive performance. our method is also validated by extensive simulation studies with five settings.

Recent advances in biological research have seen the emergence of high-throughput technologies with numerous applications that allow the study of biological mechanisms at an unprecedented depth and scale. A large amount of genomic data is now distributed through consortia like The Cancer Genome Atlas (TCGA), where specific types of biological information on specific type of tissue or cell are available. In cancer research, the challenge is now to perform integrative analyses of high-dimensional multi-omic data with the goal to better understand genomic processes that correlate with cancer outcomes, e.g. elucidate gene networks that discriminate a specific cancer subgroups (cancer sub-typing) or discovering gene networks that overlap across different cancer types (pan-cancer studies). In this paper, we propose a novel mixed graphical model approach to analyze multi-omic data of different types (continuous, discrete and count) and perform model selection by extending the Birth-Death MCMC (BDMCMC) algorithm initially proposed by Stephens (2000) and later developed by Mohammadi and Wit (2015). We compare the performance of our method to the LASSO method and the standard BDMCMC method using simulations and find that our method is superior in terms of both computational efficiency and the accuracy of the model selection results. Finally, an application to the TCGA breast cancer data shows that integrating genomic information at different levels (mutation and expression data) leads to better subtyping of breast cancers.

Accurate identification of synergistic treatment combinations and their underlying biological mechanisms is critical across many disease domains, especially cancer. In translational oncology research, preclinical systems such as patient-derived xenografts (PDX) have emerged as a unique study design evaluating multiple treatments administered to samples from the same human tumor implanted into genetically identical mice. In this paper, we propose a novel Bayesian probabilistic tree-based framework for PDX data to investigate the hierarchical relationships between treatments by inferring treatment cluster trees, referred to as treatment trees (R_x-tree). The framework motivates a new metric of mechanistic similarity between two or more treatments accounting for inherent uncertainty in tree estimation; treatments with a high estimated similarity have potentially high mechanistic synergy. Building upon Dirichlet Diffusion Trees, we derive a closed-form marginal likelihood encoding the tree structure, which facilitates computationally efficient posterior inference via a new two-stage algorithm. Simulation studies demonstrate superior performance of the proposed method in recovering the tree structure and treatment similarities. Our analyses of a recently collated PDX dataset produce treatment similarity estimates that show a high degree of concordance with known biological mechanisms across treatments in five different cancers. More importantly, we uncover new and potentially effective combination therapies that confer synergistic regulation of specific downstream biological pathways for future clinical investigations. Our accompanying code, data, and shiny application for visualization of results are available at: https://github.com/bayesrx/RxTree.

In HIV vaccine/prevention research, probing into the vaccine-induced immune responses that can help predict the risk of HIV infection provides valuable information for the development of vaccine regimens. Previous correlate analysis of the Thai vaccine trial aided the discovery of interesting immune correlates related to the risk of developing an HIV infection. The present study aimed to identify the combinations of immune responses associated with the heterogeneous infection risk. We explored a "change-plane" via combination of a subset of immune responses that could help separate vaccine recipients into two heterogeneous subgroups in terms of the association between immune responses and the risk of developing infection. Additionally, we developed a new variable selection algorithm through a penalized likelihood approach to investigate a parsimonious marker combination for the change-plane. The resulting marker combinations can serve as candidate correlates of protection and can be used for predicting the protective effect of the vaccine against HIV infection. The application of the proposed statistical approach to the Thai trial has been presented, wherein the marker combinations were explored among several immune responses and antigens.