Annals of Applied Statistics最新文献

Understanding sub-cellular protein localisation is an essential component in the analysis of context specific protein function. Recent advances in quantitative mass-spectrometry (MS) have led to high resolution mapping of thousands of proteins to sub-cellular locations within the cell. Novel modelling considerations to capture the complex nature of these data are thus necessary. We approach analysis of spatial proteomics data in a non-parametric Bayesian framework, using K-component mixtures of Gaussian process regression models. The Gaussian process regression model accounts for correlation structure within a sub-cellular niche, with each mixture component capturing the distinct correlation structure observed within each niche. The availability of marker proteins (i.e. proteins with a priori known labelled locations) motivates a semi-supervised learning approach to inform the Gaussian process hyperparameters. We moreover provide an efficient Hamiltonian-within-Gibbs sampler for our model. Furthermore, we reduce the computational burden associated with inversion of covariance matrices by exploiting the structure in the covariance matrix. A tensor decomposition of our covariance matrices allows extended Trench and Durbin algorithms to be applied to reduce the computational complexity of inversion and hence accelerate computation. We provide detailed case-studies on Drosophila embryos and mouse pluripotent embryonic stem cells to illustrate the benefit of semi-supervised functional Bayesian modelling of the data.

Late-stage clinical trials have been conducted primarily to establish the efficacy of a new treatment in an intended population. A corollary of population heterogeneity in clinical trials is that a treatment might be effective for one or more subgroups, rather than for the whole population of interest. As an example, the phase III clinical trial of panitumumab in metastatic colorectal cancer patients failed to demonstrate its efficacy in the overall population, but a subgroup associated with tumor KRAS status was found to be promising (Peeters et al. (Am. J. Clin. Oncol. 28 (2010) 4706-4713)). As we search for such subgroups via data partitioning based on a large number of biomarkers, we need to guard against inflated type I error rates due to multiple testing. Commonly-used multiplicity adjustments tend to lose power for the detection of subgroup treatment effects. We develop an effective omnibus test to detect the existence of, at least, one subgroup treatment effect, allowing a large number of possible subgroups to be considered and possibly censored outcomes. Applied to the panitumumab trial data, the proposed test would confirm a significant subgroup treatment effect. Empirical studies also show that the proposed test is applicable to a variety of outcome variables and maintains robust statistical power.

Understanding the role of time-varying pollution mixtures on human health is critical as people are simultaneously exposed to multiple pollutants during their lives. For vulnerable subpopulations who have well-defined exposure periods (e.g., pregnant women), questions regarding critical windows of exposure to these mixtures are important for mitigating harm. We extend critical window variable selection (CWVS) to the multipollutant setting by introducing CWVS for mixtures (CWVSmix), a hierarchical Bayesian method that combines smoothed variable selection and temporally correlated weight parameters to: (i) identify critical windows of exposure to mixtures of time-varying pollutants, (ii) estimate the time-varying relative importance of each individual pollutant and their first order interactions within the mixture, and (iii) quantify the impact of the mixtures on health. Through simulation we show that CWVSmix offers the best balance of performance in each of these categories in comparison to competing methods. Using these approaches, we investigate the impact of exposure to multiple ambient air pollutants on the risk of stillbirth in New Jersey, 2005-2014. We find consistent elevated risk in gestational weeks 2, 16-17, and 20 for non-Hispanic Black mothers, with pollution mixtures dominated by ammonium (weeks 2, 17, 20), nitrate (weeks 2, 17), nitrogen oxides (weeks 2, 16), PM_2.5 (week 2), and sulfate (week 20). The method is available in the R package CWVSmix.

In high-dimensional regression problems, often a relatively small subset of the features are relevant for predicting the outcome, and methods that impose sparsity on the solution are popular. When multiple correlated outcomes are available (multitask), reduced rank regression is an effective way to borrow strength and capture latent structures that underlie the data. Our proposal is motivated by the UK Biobank population-based cohort study, where we are faced with large-scale, ultrahigh-dimensional features, and have access to a large number of outcomes (phenotypes)-lifestyle measures, biomarkers, and disease outcomes. We are hence led to fit sparse reduced-rank regression models, using computational strategies that allow us to scale to problems of this size. We use a scheme that alternates between solving the sparse regression problem and solving the reduced rank decomposition. For the sparse regression component we propose a scalable iterative algorithm based on adaptive screening that leverages the sparsity assumption and enables us to focus on solving much smaller subproblems. The full solution is reconstructed and tested via an optimality condition to make sure it is a valid solution for the original problem. We further extend the method to cope with practical issues, such as the inclusion of confounding variables and imputation of missing values among the phenotypes. Experiments on both synthetic data and the UK Biobank data demonstrate the effectiveness of the method and the algorithm. We present multiSnpnet package, available at http://github.com/junyangq/multiSnpnet that works on top of PLINK2 files, which we anticipate to be a valuable tool for generating polygenic risk scores from human genetic studies.

To combat the HIV/AIDS pandemic effectively, targeted interventions among certain key populations play a critical role. Examples of such key populations include sex workers, people who inject drugs, and men who have sex with men. While having accurate estimates for the size of these key populations is important, any attempt to directly contact or count members of these populations is difficult. As a result, indirect methods are used to produce size estimates. Multiple approaches for estimating the size of such populations have been suggested but often give conflicting results. It is, therefore, necessary to have a principled way to combine and reconcile these estimates. To this end, we present a Bayesian hierarchical model for estimating the size of key populations that combines multiple estimates from different sources of information. The proposed model makes use of multiple years of data and explicitly models the systematic error in the data sources used. We use the model to estimate the size of people who inject drugs in Ukraine. We evaluate the appropriateness of the model and compare the contribution of each data source to the final estimates.

Functional magnetic resonance imaging (fMRI) has provided invaluable insight into our understanding of human behavior. However, large inter-individual differences in both brain anatomy and functional localization after anatomical alignment remain a major limitation in conducting group analyses and performing population level inference. This paper addresses this problem by developing and validating a new computational technique for reducing misalignment across individuals in functional brain systems by spatially transforming each subjects functional data to a common reference map. Our proposed Bayesian functional registration approach allows us to assess differences in brain function across subjects and individual differences in activation topology. It combines intensity-based and feature-based information into an integrated framework, and allows inference to be performed on the transformation via the posterior samples. We evaluate the method in a simulation study and apply it to data from a study of thermal pain. We find that the proposed approach provides increased sensitivity for group-level inference.

This article addresses the evaluation of post-randomization immune response biomarkers as principal surrogate endpoints of a vaccine's protective effect, based on data from randomized vaccine trials. An important metric for quantifying a biomarker's principal surrogacy in vaccine research is the vaccine efficacy curve, which shows a vaccine's efficacy as a function of potential biomarker values if receiving vaccine, among an 'early-always-at-risk' principal stratum of trial participants who remain disease-free at the time of biomarker measurement whether having received vaccine or placebo. Earlier work in principal surrogate evaluation relied on an 'equal-early-clinical-risk' assumption for identifiability of the vaccine curve, based on observed disease status at the time of biomarker measurement. This assumption is violated in the common setting that the vaccine has an early effect on the clinical endpoint before the biomarker is measured. In particular, a vaccine's early protective effect observed in two phase III dengue vaccine trials (CYD14/CYD15) has motivated our current research development. We relax the 'equal-early-clinical-risk' assumption and propose a new sensitivity analysis framework for principal surrogate evaluation allowing for early vaccine efficacy. Under this framework, we develop inference procedures for vaccine efficacy curve estimators based on the estimated maximum likelihood approach. We then use the proposed methodology to assess the surrogacy of post-randomization neutralization titer in the motivating dengue application.

Although not without controversy, readmission is entrenched as a hospital quality metric with statistical analyses generally based on fitting a logistic-Normal generalized linear mixed model. Such analyses, however, ignore death as a competing risk, although doing so for clinical conditions with high mortality can have profound effects; a hospital's seemingly good performance for readmission may be an artifact of it having poor performance for mortality. in this paper we propose novel multivariate hospital-level performance measures for readmission and mortality that derive from framing the analysis as one of cluster-correlated semi-competing risks data. We also consider a number of profiling-related goals, including the identification of extreme performers and a bivariate classification of whether the hospital has higher-/lower-than-expected readmission and mortality rates via a Bayesian decision-theoretic approach that characterizes hospitals on the basis of minimizing the posterior expected loss for an appropriate loss function. in some settings, particularly if the number of hospitals is large, the computational burden may be prohibitive. To resolve this, we propose a series of analysis strategies that will be useful in practice. Throughout, the methods are illustrated with data from CMS on N = 17,685 patients diagnosed with pancreatic cancer between 2000-2012 at one of J = 264 hospitals in California.

In the absence of a randomized experiment, a key assumption for drawing causal inference about treatment effects is the ignorable treatment assignment. Violations of the ignorability assumption may lead to biased treatment effect estimates. Sensitivity analysis helps gauge how causal conclusions will be altered in response to the potential magnitude of departure from the ignorability assumption. However, sensitivity analysis approaches for unmeasured confounding in the context of multiple treatments and binary outcomes are scarce. We propose a flexible Monte Carlo sensitivity analysis approach for causal inference in such settings. We first derive the general form of the bias introduced by unmeasured confounding, with emphasis on theoretical properties uniquely relevant to multiple treatments. We then propose methods to encode the impact of unmeasured confounding on potential outcomes and adjust the estimates of causal effects in which the presumed unmeasured confounding is removed. Our proposed methods embed nested multiple imputation within the Bayesian framework, which allow for seamless integration of the uncertainty about the values of the sensitivity parameters and the sampling variability, as well as use of the Bayesian Additive Regression Trees for modeling flexibility. Expansive simulations validate our methods and gain insight into sensitivity analysis with multiple treatments. We use the SEER-Medicare data to demonstrate sensitivity analysis using three treatments for early stage non-small cell lung cancer. The methods developed in this work are readily available in the R package SAMTx.

In order to implement disease-specific interventions in young age groups, policy makers in low- and middle-income countries require timely and accurate estimates of age- and cause-specific child mortality. High-quality data is not available in settings where these interventions are most needed, but there is a push to create sample registration systems that collect detailed mortality information. current methods that estimate mortality from this data employ multistage frameworks without rigorous statistical justification that separately estimate all-cause and cause-specific mortality and are not sufficiently adaptable to capture important features of the data. We propose a flexible Bayesian modeling framework to estimate age- and cause-specific child mortality from sample registration data. We provide a theoretical justification for the framework, explore its properties via simulation, and use it to estimate mortality trends using data from the Maternal and Child Health Surveillance System in China.