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Ander Wilson

Publications and source records attributed to Ander Wilson.

At least 19 recordsLinked to original sources

A Bayesian Functional Concurrent Zero-Inflated Dirichlet-Multinomial Regression Model with Application to Infant Microbiome

The infant microbiome undergoes rapid changes in composition over time and is associated with long-term risks of conditions such as immune strength, allergy, asthma, and other health outcomes. Modeling the associations between exposures or treatments and microbial composition over time is essential for understanding the factors that drive these changes. Estimating these temporal dynamics has several challenges including: repeated measures, overdispersion, compositionality, high-dimensional parameter spaces, and zero-inflation. Many longitudinal regression models used in human microbiome research assume constant effects over time that cannot capture time-varying or functional effects of exposures, ignore the compositional structure of the data by modeling each taxon separately, and are not equipped to handle potential zero-inflation. Dirichlet-multinomial (DM) regression models inherently accommodate overdispersion and the compositional structure of the data and have been extended to account for excess zeros. However, existing DM-based regression models are unable to additionally handle repeated measures designs. To fill this gap, we propose a functional concurrent zero-inflated Dirichlet-multinomial (FunC-ZIDM) regression model which is designed to model time-varying relations between observed covariates and microbial taxa while accounting for zero-inflation, compositionality, and repeated measures. Through simulation, we demonstrate that the model can accurately estimate the underlying functional relations and scale to large compositional spaces. We apply our model to investigate time-varying associations between infant microbiome composition and observed covariates during the 11-week postnatal period. We found that $\alpha$-diversity (i.e., diversity of the microbiome within an individual) is positively associated with a higher gestational age and percentage of breast milk in the diet.

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A Multi-Fidelity Tensor Emulator for Spatiotemporal Outputs: Emulation of Arctic Sea Ice Dynamics

Numerical models are widely used to simulate the earth system, but they are computationally expensive and often depend on many uncertain input parameters. Their effective use requires calibration and uncertainty quantification, which typically involve running the model across many input configurations and therefore incur substantial computational cost. Statistical emulation provides a practical alternative for efficiently exploring model behavior. We are motivated by the Arctic sea ice component of the Energy Exascale Earth System Model (MPAS-Seaice), which generates large spatiotemporal outputs at multiple spatial resolutions, with high-resolution (or high-fidelity, HF) simulations being more accurate but computationally more expensive than lower-resolution (low-fidelity, LF) simulations. Multi-fidelity (MF) emulation integrates information across resolutions to construct efficient and accurate surrogate models, yet existing approaches struggle to scale to large spatiotemporal data. We develop an MF emulator that combines tensor decomposition for dimensionality reduction, Gaussian process priors for flexible function approximation, and an additive discrepancy model to capture systematic differences between LF and HF data. The proposed framework enables scalable emulation while maintaining accurate predictions and well-calibrated uncertainty for complex spatiotemporal fields, and consistently achieves lower prediction error and reduced uncertainty than LF-only and HF-only models in both simulation studies and MPAS-Seaice analysis. By leveraging the complementary strengths of LF and HF data and using an efficient tensor decomposition approach, our emulator greatly reduces computational expense, making it well suited for large-scale simulation tasks involving complex physical models.

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Structured Bayesian Regression Tree Models for Estimating Distributed Lag Effects: The R Package dlmtree

When examining the relationship between an exposure and an outcome, there is often a time lag between exposure and the observed effect on the outcome. A common statistical approach for estimating the relationship between the outcome and lagged measurements of exposure is a distributed lag model (DLM). Because repeated measurements are often autocorrelated, the lagged effects are typically constrained to vary smoothly over time. A recent statistical development on the smoothing constraint is a tree structured DLM framework. We present an R package dlmtree, available on CRAN, that integrates tree structured DLM and extensions into a comprehensive software package with user-friendly implementation. A conceptual background on tree structured DLMs and demonstration of the fitting process of each model using simulated data are provided. We also demonstrate inference and interpretation using the fitted models, including summary and visualization. Additionally, a built-in shiny app for heterogeneity analysis is included.

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Distributed Lag Interaction Model with Index Modification

Epidemiological evidence supports an association between exposure to air pollution during pregnancy and birth and child health outcomes. Typically, such associations are estimated by regressing an outcome on daily or weekly measures of exposure during pregnancy using a distributed lag model. However, these associations may be modified by multiple factors. We propose a distributed lag interaction model with index modification that allows for effect modification of a functional predictor by a weighted average of multiple modifiers. Our model allows for simultaneous estimation of modifier index weights and the exposure-time-response function via a spline cross-basis in a Bayesian hierarchical framework. Through simulations, we showed that our model out-performs competing methods when there are multiple modifiers of unknown importance. We applied our proposed method to a Colorado birth cohort to estimate the association between birth weight and air pollution modified by a neighborhood-vulnerability index and to a Mexican birth cohort to estimate the association between birthing-parent cardio-metabolic endpoints and air pollution modified by a birthing-parent lifetime stress index.

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Collapsible Kernel Machine Regression for Exposomic Analyses

An important goal of environmental epidemiology is to quantify the complex health risks posed by a wide array of environmental exposures. In analyses focusing on a smaller number of exposures within a mixture, flexible models like Bayesian kernel machine regression (BKMR) are appealing because they allow for non-linear and non-additive associations among mixture components. However, this flexibility comes at the cost of low power and difficult interpretation, particularly in exposomic analyses when the number of exposures is large. We propose a flexible framework that allows for separate selection of additive and non-additive effects, unifying additive models and kernel machine regression. The proposed approach yields increased power and simpler interpretation when there is little evidence of interaction. Further, it allows users to specify separate priors for additive and non-additive effects, and allows for tests of non-additive interaction. We extend the approach to the class of multiple index models, in which the special case of kernel machine-distributed lag models are nested. We apply the method to motivating data from a subcohort of the Human Early Life Exposome (HELIX) study containing 65 mixture components grouped into 13 distinct exposure classes.

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Smooth and shape-constrained quantile distributed lag models

Exposure to environmental pollutants during the gestational period can significantly impact infant health outcomes, such as birth weight and neurological development. Identifying critical windows of susceptibility, which are specific periods during pregnancy when exposure has the most profound effects, is essential for developing targeted interventions. Distributed lag models (DLMs) are widely used in environmental epidemiology to analyze the temporal patterns of exposure and their impact on health outcomes. However, traditional DLMs focus on modeling the conditional mean, which may fail to capture heterogeneity in the relationship between predictors and the outcome. Moreover, when modeling the distribution of health outcomes like gestational birthweight, it is the extreme quantiles that are of most clinical relevance. We introduce two new quantile distributed lag model (QDLM) estimators designed to address the limitations of existing methods by leveraging smoothness and shape constraints, such as unimodality and concavity, to enhance interpretability and efficiency. We apply our QDLM estimators to the Colorado birth cohort data, demonstrating their effectiveness in identifying critical windows of susceptibility and informing public health interventions.

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Penalized Distributed Lag Interaction Model: Air Pollution, Birth Weight and Neighborhood Vulnerability

Maternal exposure to air pollution during pregnancy has a substantial public health impact. Epidemiological evidence supports an association between maternal exposure to air pollution and low birth weight. A popular method to estimate this association while identifying windows of susceptibility is a distributed lag model (DLM), which regresses an outcome onto exposure history observed at multiple time points. However, the standard DLM framework does not allow for modification of the association between repeated measures of exposure and the outcome. We propose a distributed lag interaction model that allows modification of the exposure-time-response associations across individuals by including an interaction between a continuous modifying variable and the exposure history. Our model framework is an extension of a standard DLM that uses a cross-basis, or bi-dimensional function space, to simultaneously describe both the modification of the exposure-response relationship and the temporal structure of the exposure data. Through simulations, we showed that our model with penalization out-performs a standard DLM when the true exposure-time-response associations vary by a continuous variable. Using a Colorado, USA birth cohort, we estimated the association between birth weight and ambient fine particulate matter air pollution modified by an area-level metric of health and social adversities from Colorado EnviroScreen.

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A hierarchical Bayesian model for estimating age-specific COVID-19 infection fatality rates in developing countries

The COVID-19 infection fatality rate (IFR) is the proportion of individuals infected with SARS-CoV-2 who subsequently die. As COVID-19 disproportionately affects older individuals, age-specific IFR estimates are imperative to facilitate comparisons of the impact of COVID-19 between locations and prioritize distribution of scare resources. However, there lacks a coherent method to synthesize available data to create estimates of IFR and seroprevalence that vary continuously with age and adequately reflect uncertainties inherent in the underlying data. In this paper we introduce a novel Bayesian hierarchical model to estimate IFR as a continuous function of age that acknowledges heterogeneity in population age structure across locations and accounts for uncertainty in the estimates due to seroprevalence sampling variability and the imperfect serology test assays. Our approach simultaneously models test assay characteristic, serology, and death data, where the serology and death data are often available only for binned age groups. Information is shared across locations through hierarchical modeling to improve estimation of the parameters with limited data. Modeling data from 26 developing country locations during the first year of the COVID-19 pandemic, we found seroprevalence did not change dramatically with age, and the IFR at age 60 was above the high-income country benchmark for most locations.

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Incorporating prior information into distributed lag nonlinear models with zero-inflated monotone regression trees

In environmental health research there is often interest in the effect of an exposure on a health outcome assessed on the same day and several subsequent days or lags. Distributed lag nonlinear models (DLNM) are a well-established statistical framework for estimating an exposure-lag-response function. We propose methods to allow for prior information to be incorporated into DLNMs. First, we impose a monotonicity constraint in the exposure-response at lagged time periods which matches with knowledge on how biological mechanisms respond to increased levels of exposures. Second, we introduce variable selection into the DLNM to identify lagged periods of susceptibility with respect to the outcome of interest. The variable selection approach allows for direct application of informative priors on which lags have nonzero association with the outcome. We propose a tree-of-trees model that uses two layers of trees: one for splitting the exposure time frame and one for fitting exposure-response functions over different time periods. We introduce a zero-inflated alternative to the tree splitting prior in Bayesian additive regression trees to allow for lag selection and the addition of informative priors. We develop a computational approach for efficient posterior sampling and perform a comprehensive simulation study to compare our method to existing DLNM approaches. We apply our method to estimate time-lagged extreme temperature relationships with mortality during summer or winter in Chicago, IL.

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Infinite Hidden Markov Models for Multiple Multivariate Time Series with Missing Data

Exposure to air pollution is associated with increased morbidity and mortality. Recent technological advancements permit the collection of time-resolved personal exposure data. Such data are often incomplete with missing observations and exposures below the limit of detection, which limit their use in health effects studies. In this paper we develop an infinite hidden Markov model for multiple asynchronous multivariate time series with missing data. Our model is designed to include covariates that can inform transitions among hidden states. We implement beam sampling, a combination of slice sampling and dynamic programming, to sample the hidden states, and a Bayesian multiple imputation algorithm to impute missing data. In simulation studies, our model excels in estimating hidden states and state-specific means and imputing observations that are missing at random or below the limit of detection. We validate our imputation approach on data from the Fort Collins Commuter Study. We show that the estimated hidden states improve imputations for data that are missing at random compared to existing approaches. In a case study of the Fort Collins Commuter Study, we describe the inferential gains obtained from our model including improved imputation of missing data and the ability to identify shared patterns in activity and exposure among repeated sampling days for individuals and among distinct individuals.

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Integrating Biological Knowledge in Kernel-Based Analyses of Environmental Mixtures and Health

A key goal of environmental health research is to assess the risk posed by mixtures of pollutants. As epidemiologic studies of mixtures can be expensive to conduct, it behooves researchers to incorporate prior knowledge about mixtures into their analyses. This work extends the Bayesian multiple index model (BMIM), which assumes the exposure-response function is a non-parametric function of a set of linear combinations of pollutants formed with a set of exposure-specific weights. The framework is attractive because it combines the flexibility of response-surface methods with the interpretability of linear index models. We propose three strategies to incorporate prior toxicological knowledge into construction of indices in a BMIM: (a) constraining index weights, (b) structuring index weights by exposure transformations, and (c) placing informative priors on the index weights. We propose a novel prior specification that combines spike-and-slab variable selection with informative Dirichlet distribution based on relative potency factors often derived from previous toxicological studies. In simulations we show that the proposed priors improve inferences when prior information is correct and can protect against misspecification suffered by naive toxicological models when prior information is incorrect. Moreover, different strategies may be mixed-and-matched for different indices to suit available information (or lack thereof). We demonstrate the proposed methods on an analysis of data from the National Health and Nutrition Examination Survey and incorporate prior information on relative chemical potencies obtained from toxic equivalency factors available in the literature.

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Heterogeneous Distributed Lag Models to Estimate Personalized Effects of Maternal Exposures to Air Pollution

Children's health studies support an association between maternal environmental exposures and children's birth outcomes. A common goal is to identify critical windows of susceptibility--periods during gestation with increased association between maternal exposures and a future outcome. The timing of the critical windows and magnitude of the associations are likely heterogeneous across different levels of individual, family, and neighborhood characteristics. Using an administrative Colorado birth cohort we estimate the individualized relationship between weekly exposures to fine particulate matter (PM$_{2.5}$) during gestation and birth weight. To achieve this goal, we propose a statistical learning method combining distributed lag models and Bayesian additive regression trees to estimate critical windows at the individual level and identify characteristics that induce heterogeneity from a high-dimensional set of potential modifying factors. We find evidence of heterogeneity in the PM$_{2.5}$-birth weight relationship, with some mother-child dyads showing a 3 times larger decrease in birth weight for an IQR increase in exposure (5.9 to 8.5 $\mu g/m^3$ PM$_{2.5}$) compared to the population average. Specifically, we find increased susceptibility for non-Hispanic mothers who are either younger, have higher body mass index or lower educational attainment. Our case study is the first precision health study of critical windows.

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Kernel Machine and Distributed Lag Models for Assessing Windows of Susceptibility to Environmental Mixtures in Children's Health Studies

Exposures to environmental chemicals during gestation can alter health status later in life. Most studies of maternal exposure to chemicals during pregnancy have focused on a single chemical exposure observed at high temporal resolution. Recent research has turned to focus on exposure to mixtures of multiple chemicals, generally observed at a single time point. We consider statistical methods for analyzing data on chemical mixtures that are observed at a high temporal resolution. As motivation, we analyze the association between exposure to four ambient air pollutants observed weekly throughout gestation and birth weight in a Boston-area prospective birth cohort. To explore patterns in the data, we first apply methods for analyzing data on (1) a single chemical observed at high temporal resolution, and (2) a mixture measured at a single point in time. We highlight the shortcomings of these approaches for temporally-resolved data on exposure to chemical mixtures. Second, we propose a novel method, a Bayesian kernel machine regression distributed lag model (BKMR-DLM), that simultaneously accounts for nonlinear associations and interactions among time-varying measures of exposure to mixtures. BKMR-DLM uses a functional weight for each exposure that parameterizes the window of susceptibility corresponding to that exposure within a kernel machine framework that captures non-linear and interaction effects of the multivariate exposure on the outcome. In a simulation study, we show that the proposed method can better estimate the exposure-response function and, in high signal settings, can identify critical windows in time during which exposure has an increased association with the outcome. Applying the proposed method to the Boston birth cohort data, we find evidence of a negative association between organic carbon and birth weight and that nitrate modifies the organic carbon, ...

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Multiple exposure distributed lag models with variable selection

Distributed lag models are useful in environmental epidemiology as they allow the user to investigate critical windows of exposure, defined as the time period during which exposure to a pollutant adversely affects health outcomes. Recent studies have focused on estimating the health effects of a large number of environmental exposures, or an environmental mixture, on health outcomes. In such settings, it is important to understand which environmental exposures affect a particular outcome, while acknowledging the possibility that different exposures have different critical windows. Further, in the studies of environmental mixtures, it is important to identify interactions among exposures, and to account for the fact that this interaction may occur between two exposures having different critical windows. Exposure to one exposure early in time could cause an individual to be more or less susceptible to another exposure later in time. We propose a Bayesian model to estimate the temporal effects of a large number of exposures on an outcome. We use spike-and-slab priors and semiparametric distributed lag curves to identify important exposures and exposure interactions, and discuss extensions with improved power to detect harmful exposures. We then apply these methods to estimate the effects of exposure to multiple air pollutants during pregnancy on birthweight from vital records in Colorado.

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Estimating Perinatal Critical Windows of Susceptibility to Environmental Mixtures via Structured Bayesian Regression Tree Pairs

Maternal exposure to environmental chemicals during pregnancy can alter birth and children's health outcomes. Research seeks to identify critical windows, time periods when the exposures can change future health outcomes, and estimate the exposure-response relationship. Existing statistical approaches focus on estimation of the association between maternal exposure to a single environmental chemical observed at high-temporal resolution, such as weekly throughout pregnancy, and children's health outcomes. Extending to multiple chemicals observed at high temporal resolution poses a dimensionality problem and statistical methods are lacking. We propose a tree-based model for mixtures of exposures that are observed at high temporal resolution. The proposed approach uses an additive ensemble of structured tree-pairs that define structured main effects and interactions between time-resolved predictors and variable selection to select out of the model predictors not correlated with the outcome. We apply our method in a simulation and the analysis of the relationship between five exposures measured weekly throughout pregnancy and resulting birth weight in a Denver, Colorado birth cohort. We identified critical windows during which fine particulate matter, sulfur dioxide, and temperature are negatively associated with birth weight and an interaction between fine particulate matter and temperature. Software is made available in the R package dlmtree.

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Treed distributed lag nonlinear models

In studies of maternal exposure to air pollution a children's health outcome is regressed on exposures observed during pregnancy. The distributed lag nonlinear model (DLNM) is a statistical method commonly implemented to estimate an exposure-time-response function when it is postulated the exposure effect is nonlinear. Previous implementations of the DLNM estimate an exposure-time-response surface parameterized with a bivariate basis expansion. However, basis functions such as splines assume smoothness across the entire exposure-time-response surface, which may be unrealistic in settings where the exposure is associated with the outcome only in a specific time window. We propose a framework for estimating the DLNM based on Bayesian additive regression trees. Our method operates using a set of regression trees that each assume piecewise constant relationships across the exposure-time space. In a simulation, we show that our model outperforms spline-based models when the exposure-time surface is not smooth, while both methods perform similarly in settings where the true surface is smooth. Importantly, the proposed approach is lower variance and more precisely identifies critical windows during which exposure is associated with a future health outcome. We apply our method to estimate the association between maternal exposure to PM$_{2.5}$ and birth weight in a Colorado USA birth cohort.

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Bayesian Multiple Index Models for Environmental Mixtures

An important goal of environmental health research is to assess the risk posed by mixtures of environmental exposures. Two popular classes of models for mixtures analyses are response-surface methods and exposure-index methods. Response-surface methods estimate high-dimensional surfaces and are thus highly flexible but difficult to interpret. In contrast, exposure-index methods decompose coefficients from a linear model into an overall mixture effect and individual index weights; these models yield easily interpretable effect estimates and efficient inferences when model assumptions hold, but, like most parsimonious models, incur bias when these assumptions do not hold. In this paper we propose a Bayesian multiple index model framework that combines the strengths of each, allowing for non-linear and non-additive relationships between exposure indices and a health outcome, while reducing the dimensionality of the exposure vector and estimating index weights with variable selection. This framework contains response-surface and exposure-index models as special cases, thereby unifying the two analysis strategies. This unification increases the range of models possible for analyzing environmental mixtures and health, allowing one to select an appropriate analysis from a spectrum of models varying in flexibility and interpretability. In an analysis of the association between telomere length and 18 organic pollutants in the National Health and Nutrition Examination Survey (NHANES), the proposed approach fits the data as well as more complex response-surface methods and yields more interpretable results.

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Bayesian Nonparametric Monotone Regression

In many applications there is interest in estimating the relation between a predictor and an outcome when the relation is known to be monotone or otherwise constrained due to the physical processes involved. We consider one such application--inferring time-resolved aerosol concentration from a low-cost differential pressure sensor. The objective is to estimate a monotone function and make inference on the scaled first derivative of the function. We proposed Bayesian nonparametric monotone regression which uses a Bernstein polynomial basis to construct the regression function and puts a Dirichlet process prior on the regression coefficients. The base measure of the Dirichlet process is a finite mixture of a mass point at zero and a truncated normal. This construction imposes monotonicity while clustering the basis functions. Clustering the basis functions reduces the parameter space and allows the estimated regression function to be linear. With the proposed approach we can make closed-formed inference on the derivative of the estimated function including full quantification of uncertainty. In a simulation study the proposed method performs similar to other monotone regression approaches when the true function is wavy but performs better when the true function is linear. We apply the method to estimate time-resolved aerosol concentration with a newly-developed portable aerosol monitor. The R package bnmr is made available to implement the method.

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