Peng Shi, Zifeng Zhao.

Source: The Annals of Applied Statistics, Volume 14, Number 1, 357--380.

Abstract:
In actuarial research a task of particular interest and importance is to predict the loss cost for individual risks so that informative decisions are made in various insurance operations such as underwriting, ratemaking and capital management. The loss cost is typically viewed to follow a compound distribution where the summation of the severity variables is stopped by the frequency variable. A challenging issue in modeling such outcomes is to accommodate the potential dependence between the number of claims and the size of each individual claim. In this article we introduce a novel regression framework for compound distributions that uses a copula to accommodate the association between the frequency and the severity variables and, thus, allows for arbitrary dependence between the two components. We further show that the new model is very flexible and is easily modified to account for incomplete data due to censoring or truncation. The flexibility of the proposed model is illustrated using both simulated and real data sets. In the analysis of granular claims data from property insurance, we find substantive negative relationship between the number and the size of insurance claims. In addition, we demonstrate that ignoring the frequency-severity association could lead to biased decision-making in insurance operations.

Medha Uppala, Mark S. Handcock.

Source: The Annals of Applied Statistics, Volume 14, Number 1, 339--356.

Abstract:
This paper focuses on spatial and temporal modeling of point processes on linear networks. Point processes on linear networks can simply be defined as point events occurring on or near line segment network structures embedded in a certain space. A separable modeling framework is introduced that posits separate formation and dissolution models of point processes on linear networks over time. While the model was inspired by spider web building activity in brick mortar lines, the focus is on modeling wildfire ignition origins near road networks over a span of 14 years. As most wildfires in California have human-related origins, modeling the origin locations with respect to the road network provides insight into how human, vehicular and structural densities affect ignition occurrence. Model results show that roads that traverse different types of regions such as residential, interface and wildland regions have higher ignition intensities compared to roads that only exist in each of the mentioned region types.

Jared D. Fisher, Davide Pettenuzzo, Carlos M. Carvalho.

Source: The Annals of Applied Statistics, Volume 14, Number 1, 299--338.

Abstract:
We introduce a fast, closed-form, simulation-free method to model and forecast multiple asset returns and employ it to investigate the optimal ensemble of features to include when jointly predicting monthly stock and bond excess returns. Our approach builds on the Bayesian dynamic linear models of West and Harrison ( Bayesian Forecasting and Dynamic Models (1997) Springer), and it can objectively determine, through a fully automated procedure, both the optimal set of regressors to include in the predictive system and the degree to which the model coefficients, volatilities and covariances should vary over time. When applied to a portfolio of five stock and bond returns, we find that our method leads to large forecast gains, both in statistical and economic terms. In particular, we find that relative to a standard no-predictability benchmark, the optimal combination of predictors, stochastic volatility and time-varying covariances increases the annualized certainty equivalent returns of a leverage-constrained power utility investor by more than 500 basis points.

Wanghuan Chu, Runze Li, Jingyuan Liu, Matthew Reimherr.

Source: The Annals of Applied Statistics, Volume 14, Number 1, 276--298.

Abstract:
Motivated by an empirical analysis of data from a genome-wide association study on obesity, measured by the body mass index (BMI), we propose a two-step gene-detection procedure for generalized varying coefficient mixed-effects models with ultrahigh dimensional covariates. The proposed procedure selects significant single nucleotide polymorphisms (SNPs) impacting the mean BMI trend, some of which have already been biologically proven to be “fat genes.” The method also discovers SNPs that significantly influence the age-dependent variability of BMI. The proposed procedure takes into account individual variations of genetic effects and can also be directly applied to longitudinal data with continuous, binary or count responses. We employ Monte Carlo simulation studies to assess the performance of the proposed method and further carry out causal inference for the selected SNPs.

Joseph Antonelli, Maitreyi Mazumdar, David Bellinger, David Christiani, Robert Wright, Brent Coull.

Source: The Annals of Applied Statistics, Volume 14, Number 1, 257--275.

Abstract:
Humans are routinely exposed to mixtures of chemical and other environmental factors, making the quantification of health effects associated with environmental mixtures a critical goal for establishing environmental policy sufficiently protective of human health. The quantification of the effects of exposure to an environmental mixture poses several statistical challenges. It is often the case that exposure to multiple pollutants interact with each other to affect an outcome. Further, the exposure-response relationship between an outcome and some exposures, such as some metals, can exhibit complex, nonlinear forms, since some exposures can be beneficial and detrimental at different ranges of exposure. To estimate the health effects of complex mixtures, we propose a flexible Bayesian approach that allows exposures to interact with each other and have nonlinear relationships with the outcome. We induce sparsity using multivariate spike and slab priors to determine which exposures are associated with the outcome and which exposures interact with each other. The proposed approach is interpretable, as we can use the posterior probabilities of inclusion into the model to identify pollutants that interact with each other. We utilize our approach to study the impact of exposure to metals on child neurodevelopment in Bangladesh and find a nonlinear, interactive relationship between arsenic and manganese.

Tsuyoshi Kunihama, Zehang Richard Li, Samuel J. Clark, Tyler H. McCormick.

Source: The Annals of Applied Statistics, Volume 14, Number 1, 241--256.

Abstract:
The distribution of deaths by cause provides crucial information for public health planning, response and evaluation. About 60% of deaths globally are not registered or given a cause, limiting our ability to understand disease epidemiology. Verbal autopsy (VA) surveys are increasingly used in such settings to collect information on the signs, symptoms and medical history of people who have recently died. This article develops a novel Bayesian method for estimation of population distributions of deaths by cause using verbal autopsy data. The proposed approach is based on a multivariate probit model where associations among items in questionnaires are flexibly induced by latent factors. Using the Population Health Metrics Research Consortium labeled data that include both VA and medically certified causes of death, we assess performance of the proposed method. Further, we estimate important questionnaire items that are highly associated with causes of death. This framework provides insights that will simplify future data

Mohamad Elmasri, Maxwell J. Farrell, T. Jonathan Davies, David A. Stephens.

Source: The Annals of Applied Statistics, Volume 14, Number 1, 221--240.

Abstract:
Identifying undocumented or potential future interactions among species is a challenge facing modern ecologists. Recent link prediction methods rely on trait data; however, large species interaction databases are typically sparse and covariates are limited to only a fraction of species. On the other hand, evolutionary relationships, encoded as phylogenetic trees, can act as proxies for underlying traits and historical patterns of parasite sharing among hosts. We show that, using a network-based conditional model, phylogenetic information provides strong predictive power in a recently published global database of host-parasite interactions. By scaling the phylogeny using an evolutionary model, our method allows for biological interpretation often missing from latent variable models. To further improve on the phylogeny-only model, we combine a hierarchical Bayesian latent score framework for bipartite graphs that accounts for the number of interactions per species with host dependence informed by phylogeny. Combining the two information sources yields significant improvement in predictive accuracy over each of the submodels alone. As many interaction networks are constructed from presence-only data, we extend the model by integrating a correction mechanism for missing interactions which proves valuable in reducing uncertainty in unobserved interactions.

Kerstin Spitzer, Marta Pelizzola, Andreas Futschik.

Source: The Annals of Applied Statistics, Volume 14, Number 1, 202--220.

Abstract:
Evolve and resequence studies provide a popular approach to simulate evolution in the lab and explore its genetic basis. In this context, Pearson’s chi-square test, Fisher’s exact test as well as the Cochran–Mantel–Haenszel test are commonly used to infer genomic positions affected by selection from temporal changes in allele frequency. However, the null model associated with these tests does not match the null hypothesis of actual interest. Indeed, due to genetic drift and possibly other additional noise components such as pool sequencing, the null variance in the data can be substantially larger than accounted for by these common test statistics. This leads to $p$-values that are systematically too small and, therefore, a huge number of false positive results. Even, if the ranking rather than the actual $p$-values is of interest, a naive application of the mentioned tests will give misleading results, as the amount of overdispersion varies from locus to locus. We therefore propose adjusted statistics that take the overdispersion into account while keeping the formulas simple. This is particularly useful in genome-wide applications, where millions of SNPs can be handled with little computational effort. We then apply the adapted test statistics to real data from Drosophila and investigate how information from intermediate generations can be included when available. We also discuss further applications such as genome-wide association studies based on pool sequencing data and tests for local adaptation.

Hong Zhang, Tiejun Tong, John Landers, Zheyang Wu.

Source: The Annals of Applied Statistics, Volume 14, Number 1, 178--201.

Abstract:
The $p$-value combination approach is an important statistical strategy for testing global hypotheses with broad applications in signal detection, meta-analysis, data integration, etc. In this paper we extend the classic Fisher’s combination method to a unified family of statistics, called TFisher, which allows a general truncation-and-weighting scheme of input $p$-values. TFisher can significantly improve statistical power over the Fisher and related truncation-only methods for detecting both rare and dense “signals.” To address wide applications, analytical calculations for TFisher’s size and power are deduced under any two continuous distributions in the null and the alternative hypotheses. The corresponding omnibus test (oTFisher) and its size calculation are also provided for data-adaptive analysis. We study the asymptotic optimal parameters of truncation and weighting based on Bahadur efficiency (BE). A new asymptotic measure, called the asymptotic power efficiency (APE), is also proposed for better reflecting the statistics’ performance in real data analysis. Interestingly, under the Gaussian mixture model in the signal detection problem, both BE and APE indicate that the soft-thresholding scheme is the best, the truncation and weighting parameters should be equal. By simulations of various signal patterns, we systematically compare the power of statistics within TFisher family as well as some rare-signal-optimal tests. We illustrate the use of TFisher in an exome-sequencing analysis for detecting novel genes of amyotrophic lateral sclerosis. Relevant computation has been implemented into an R package TFisher published on the Comprehensive R Archive Network to cater for applications.

Chih-Yuan Hsu, Yi-Hau Chen, Ruoh-Rong Yu, Tsung-Wei Hung.

Source: The Annals of Applied Statistics, Volume 14, Number 1, 160--177.

Abstract:
Workers in Taiwan overall have been suffering from long-lasting wage stagnation since the mid-1990s. In particular, there seems to be little mobility for the wages of Taiwanese workers to transit across wage quantile groups. It is of interest to see if certain groups of workers, such as female, lower educated and younger generation workers, suffer from the problem more seriously than the others. This work tries to apply a systematic statistical approach to study this issue, based on the longitudinal data from the Panel Study of Family Dynamics (PSFD) survey conducted in Taiwan since 1999. We propose the quantile transition regression model, generalizing recent methodology for quantile association, to assess the wage status transition with respect to the marginal wage quantiles over time as well as the effects of certain demographic and job factors on the wage status transition. Estimation of the model can be based on the composite likelihoods utilizing the binary, or ordinal-data information regarding the quantile transition, with the associated asymptotic theory established. A goodness-of-fit procedure for the proposed model is developed. The performances of the estimation and the goodness-of-fit procedures for the quantile transition model are illustrated through simulations. The application of the proposed methodology to the PSFD survey data suggests that female, private-sector workers with higher age and education below postgraduate level suffer from more severe wage status stagnation than the others.

Zhenguo Gao, Pang Du, Ran Jin, John L. Robertson.

Source: The Annals of Applied Statistics, Volume 14, Number 1, 143--159.

Abstract:
Liver procurement experiments with surface-temperature monitoring motivated Gao et al. ( J. Amer. Statist. Assoc. 114 (2019) 773–781) to develop a variance change-point detection method under a smoothly-changing mean trend. However, the spotwise change points yielded from their method do not offer immediate information to surgeons since an organ is often transplanted as a whole or in part. We develop a new practical method that can analyze a defined portion of the organ surface at a time. It also provides a novel addition to the developing field of functional data monitoring. Furthermore, numerical challenge emerges for simultaneously modeling the variance functions of 2D locations and the mean function of location and time. The respective sample sizes in the scales of 10,000 and 1,000,000 for modeling these functions make standard spline estimation too costly to be useful. We introduce a multistage subsampling strategy with steps educated by quickly-computable preliminary statistical measures. Extensive simulations show that the new method can efficiently reduce the computational cost and provide reasonable parameter estimates. Application of the new method to our liver surface temperature monitoring data shows its effectiveness in providing accurate status change information for a selected portion of the organ in the experiment.

Arnab Chakraborty, Soumendra Nath Lahiri, Alyson Wilson.

Source: The Annals of Applied Statistics, Volume 14, Number 1, 116--142.

Abstract:
Spatial prediction of weather elements like temperature, precipitation, and barometric pressure are generally based on satellite imagery or data collected at ground stations. None of these data provide information at a more granular or “hyperlocal” resolution. On the other hand, crowdsourced weather data, which are captured by sensors installed on mobile devices and gathered by weather-related mobile apps like WeatherSignal and AccuWeather, can serve as potential data sources for analyzing environmental processes at a hyperlocal resolution. However, due to the low quality of the sensors and the nonlaboratory environment, the quality of the observations in crowdsourced data is compromised. This paper describes methods to improve hyperlocal spatial prediction using this varying-quality, noisy crowdsourced information. We introduce a reliability metric, namely Veracity Score (VS), to assess the quality of the crowdsourced observations using a coarser, but high-quality, reference data. A VS-based methodology to analyze noisy spatial data is proposed and evaluated through extensive simulations. The merits of the proposed approach are illustrated through case studies analyzing crowdsourced daily average ambient temperature readings for one day in the contiguous United States.

Bryan D. Martin, Daniela Witten, Amy D. Willis.

Source: The Annals of Applied Statistics, Volume 14, Number 1, 94--115.

Abstract:
Using a sample from a population to estimate the proportion of the population with a certain category label is a broadly important problem. In the context of microbiome studies, this problem arises when researchers wish to use a sample from a population of microbes to estimate the population proportion of a particular taxon, known as the taxon’s relative abundance . In this paper, we propose a beta-binomial model for this task. Like existing models, our model allows for a taxon’s relative abundance to be associated with covariates of interest. However, unlike existing models, our proposal also allows for the overdispersion in the taxon’s counts to be associated with covariates of interest. We exploit this model in order to propose tests not only for differential relative abundance, but also for differential variability. The latter is particularly valuable in light of speculation that dysbiosis , the perturbation from a normal microbiome that can occur in certain disease conditions, may manifest as a loss of stability, or increase in variability, of the counts associated with each taxon. We demonstrate the performance of our proposed model using a simulation study and an application to soil microbial data.

Paul J. Birrell, Lorenz Wernisch, Brian D. M. Tom, Leonhard Held, Gareth O. Roberts, Richard G. Pebody, Daniela De Angelis.

Source: The Annals of Applied Statistics, Volume 14, Number 1, 74--93.

Abstract:
A prompt public health response to a new epidemic relies on the ability to monitor and predict its evolution in real time as data accumulate. The 2009 A/H1N1 outbreak in the UK revealed pandemic data as noisy, contaminated, potentially biased and originating from multiple sources. This seriously challenges the capacity for real-time monitoring. Here, we assess the feasibility of real-time inference based on such data by constructing an analytic tool combining an age-stratified SEIR transmission model with various observation models describing the data generation mechanisms. As batches of data become available, a sequential Monte Carlo (SMC) algorithm is developed to synthesise multiple imperfect data streams, iterate epidemic inferences and assess model adequacy amidst a rapidly evolving epidemic environment, substantially reducing computation time in comparison to standard MCMC, to ensure timely delivery of real-time epidemic assessments. In application to simulated data designed to mimic the 2009 A/H1N1 epidemic, SMC is shown to have additional benefits in terms of assessing predictive performance and coping with parameter nonidentifiability.

Wenjie Wang, Robert Aseltine, Kun Chen, Jun Yan.

Source: The Annals of Applied Statistics, Volume 14, Number 1, 51--73.

Abstract:
The concept of integrating data from disparate sources to accelerate scientific discovery has generated tremendous excitement in many fields. The potential benefits from data integration, however, may be compromised by the uncertainty due to incomplete/imperfect record linkage. Motivated by a suicide risk study, we propose an approach for analyzing survival data with uncertain event times arising from data integration. Specifically, in our problem deaths identified from the hospital discharge records together with reported suicidal deaths determined by the Office of Medical Examiner may still not include all the death events of patients, and the missing deaths can be recovered from a complete database of death records. Since the hospital discharge data can only be linked to the death record data by matching basic patient characteristics, a patient with a censored death time from the first dataset could be linked to multiple potential event records in the second dataset. We develop an integrative Cox proportional hazards regression in which the uncertainty in the matched event times is modeled probabilistically. The estimation procedure combines the ideas of profile likelihood and the expectation conditional maximization algorithm (ECM). Simulation studies demonstrate that under realistic settings of imperfect data linkage the proposed method outperforms several competing approaches including multiple imputation. A marginal screening analysis using the proposed integrative Cox model is performed to identify risk factors associated with death following suicide-related hospitalization in Connecticut. The identified diagnostics codes are consistent with existing literature and provide several new insights on suicide risk, prediction and prevention.

Jennifer E. Starling, Jared S. Murray, Carlos M. Carvalho, Radek K. Bukowski, James G. Scott.

Source: The Annals of Applied Statistics, Volume 14, Number 1, 28--50.

Abstract:
This article introduces BART with Targeted Smoothing, or tsBART, a new Bayesian tree-based model for nonparametric regression. The goal of tsBART is to introduce smoothness over a single target covariate $t$ while not necessarily requiring smoothness over other covariates $x$. tsBART is based on the Bayesian Additive Regression Trees (BART) model, an ensemble of regression trees. tsBART extends BART by parameterizing each tree’s terminal nodes with smooth functions of $t$ rather than independent scalars. Like BART, tsBART captures complex nonlinear relationships and interactions among the predictors. But unlike BART, tsBART guarantees that the response surface will be smooth in the target covariate. This improves interpretability and helps to regularize the estimate. After introducing and benchmarking the tsBART model, we apply it to our motivating example—pregnancy outcomes data from the National Center for Health Statistics. Our aim is to provide patient-specific estimates of stillbirth risk across gestational age $(t)$ and based on maternal and fetal risk factors $(x)$. Obstetricians expect stillbirth risk to vary smoothly over gestational age but not necessarily over other covariates, and tsBART has been designed precisely to reflect this structural knowledge. The results of our analysis show the clear superiority of the tsBART model for quantifying stillbirth risk, thereby providing patients and doctors with better information for managing the risk of fetal mortality. All methods described here are implemented in the R package tsbart .

Francisco J. R. Ruiz, Susan Athey, David M. Blei.

Source: The Annals of Applied Statistics, Volume 14, Number 1, 1--27.

Abstract:
We develop SHOPPER, a sequential probabilistic model of shopping data. SHOPPER uses interpretable components to model the forces that drive how a customer chooses products; in particular, we designed SHOPPER to capture how items interact with other items. We develop an efficient posterior inference algorithm to estimate these forces from large-scale data, and we analyze a large dataset from a major chain grocery store. We are interested in answering counterfactual queries about changes in prices. We found that SHOPPER provides accurate predictions even under price interventions, and that it helps identify complementary and substitutable pairs of products.

Joe Watson, James V. Zidek, Gavin Shaddick.

Source: The Annals of Applied Statistics, Volume 13, Number 4, 2662--2700.

Abstract:
This paper presents a general model framework for detecting the preferential sampling of environmental monitors recording an environmental process across space and/or time. This is achieved by considering the joint distribution of an environmental process with a site-selection process that considers where and when sites are placed to measure the process. The environmental process may be spatial, temporal or spatio-temporal in nature. By sharing random effects between the two processes, the joint model is able to establish whether site placement was stochastically dependent of the environmental process under study. Furthermore, if stochastic dependence is identified between the two processes, then inferences about the probability distribution of the spatio-temporal process will change, as will predictions made of the process across space and time. The embedding into a spatio-temporal framework also allows for the modelling of the dynamic site-selection process itself. Real-world factors affecting both the size and location of the network can be easily modelled and quantified. Depending upon the choice of the population of locations considered for selection across space and time under the site-selection process, different insights about the precise nature of preferential sampling can be obtained. The general framework developed in the paper is designed to be easily and quickly fit using the R-INLA package. We apply this framework to a case study involving particulate air pollution over the UK where a major reduction in the size of a monitoring network through time occurred. It is demonstrated that a significant response-biased reduction in the air quality monitoring network occurred, namely the relocation of monitoring sites to locations with the highest pollution levels, and the routine removal of sites at locations with the lowest. We also show that the network was consistently unrepresenting levels of particulate matter seen across much of GB throughout the operating life of the network. Finally we show that this may have led to a severe overreporting of the population-average exposure levels experienced across GB. This could have great impacts on estimates of the health effects of black smoke levels.

Elizabeth Lorenzi, Ricardo Henao, Katherine Heller.

Source: The Annals of Applied Statistics, Volume 13, Number 4, 2637--2661.

Abstract:
Nearly a third of all surgeries performed in the United States occur for patients over the age of 65; these older adults experience a higher rate of postoperative morbidity and mortality. To improve the care for these patients, we aim to identify and characterize high risk geriatric patients to send to a specialized perioperative clinic while leveraging the overall surgical population to improve learning. To this end, we develop a hierarchical infinite latent factor model (HIFM) to appropriately account for the covariance structure across subpopulations in data. We propose a novel Hierarchical Dirichlet Process shrinkage prior on the loadings matrix that flexibly captures the underlying structure of our data while sharing information across subpopulations to improve inference and prediction. The stick-breaking construction of the prior assumes an infinite number of factors and allows for each subpopulation to utilize different subsets of the factor space and select the number of factors needed to best explain the variation. We develop the model into a latent factor regression method that excels at prediction and inference of regression coefficients. Simulations validate this strong performance compared to baseline methods. We apply this work to the problem of predicting surgical complications using electronic health record data for geriatric patients and all surgical patients at Duke University Health System (DUHS). The motivating application demonstrates the improved predictive performance when using HIFM in both area under the ROC curve and area under the PR Curve while providing interpretable coefficients that may lead to actionable interventions.

Li Zhu, Zhiguang Huo, Tianzhou Ma, Steffi Oesterreich, George C. Tseng.

Source: The Annals of Applied Statistics, Volume 13, Number 4, 2611--2636.

Abstract:
Variable selection is a pervasive problem in modern high-dimensional data analysis where the number of features often exceeds the sample size (a.k.a. small-n-large-p problem). Incorporation of group structure knowledge to improve variable selection has been widely studied. Here, we consider prior knowledge of a hierarchical overlapping group structure to improve variable selection in regression setting. In genomics applications, for instance, a biological pathway contains tens to hundreds of genes and a gene can be mapped to multiple experimentally measured features (such as its mRNA expression, copy number variation and methylation levels of possibly multiple sites). In addition to the hierarchical structure, the groups at the same level may overlap (e.g., two pathways can share common genes). Incorporating such hierarchical overlapping groups in traditional penalized regression setting remains a difficult optimization problem. Alternatively, we propose a Bayesian indicator model that can elegantly serve the purpose. We evaluate the model in simulations and two breast cancer examples, and demonstrate its superior performance over existing models. The result not only enhances prediction accuracy but also improves variable selection and model interpretation that lead to deeper biological insight of the disease.

Silvia Metelli, Nicholas Heard.

Source: The Annals of Applied Statistics, Volume 13, Number 4, 2586--2610.

Abstract:
Monitoring computer network traffic for anomalous behaviour presents an important security challenge. Arrivals of new edges in a network graph represent connections between a client and server pair not previously observed, and in rare cases these might suggest the presence of intruders or malicious implants. We propose a Bayesian model and anomaly detection method for simultaneously characterising existing network structure and modelling likely new edge formation. The method is demonstrated on real computer network authentication data and successfully identifies some machines which are known to be compromised.

Seth Flaxman, Michael Chirico, Pau Pereira, Charles Loeffler.

Source: The Annals of Applied Statistics, Volume 13, Number 4, 2564--2585.

Abstract:
We propose a generic spatiotemporal event forecasting method which we developed for the National Institute of Justice’s (NIJ) Real-Time Crime Forecasting Challenge (National Institute of Justice (2017)). Our method is a spatiotemporal forecasting model combining scalable randomized Reproducing Kernel Hilbert Space (RKHS) methods for approximating Gaussian processes with autoregressive smoothing kernels in a regularized supervised learning framework. While the smoothing kernels capture the two main approaches in current use in the field of crime forecasting, kernel density estimation (KDE) and self-exciting point process (SEPP) models, the RKHS component of the model can be understood as an approximation to the popular log-Gaussian Cox Process model. For inference, we discretize the spatiotemporal point pattern and learn a log-intensity function using the Poisson likelihood and highly efficient gradient-based optimization methods. Model hyperparameters including quality of RKHS approximation, spatial and temporal kernel lengthscales, number of autoregressive lags and bandwidths for smoothing kernels as well as cell shape, size and rotation, were learned using cross validation. Resulting predictions significantly exceeded baseline KDE estimates and SEPP models for sparse events.

Liberty Vittert, Adrian W. Bowman, Stanislav Katina.

Source: The Annals of Applied Statistics, Volume 13, Number 4, 2539--2563.

Abstract:
One of the data structures generated by medical imaging technology is high resolution point clouds representing anatomical surfaces. Stereophotogrammetry and laser scanning are two widely available sources of this kind of data. A standardised surface representation is required to provide a meaningful correspondence across different images as a basis for statistical analysis. Point locations with anatomical definitions, referred to as landmarks, have been the traditional approach. Landmarks can also be taken as the starting point for more general surface representations, often using templates which are warped on to an observed surface by matching landmark positions and subsequent local adjustment of the surface. The aim of the present paper is to provide a new approach which places anatomical curves at the heart of the surface representation and its analysis. Curves provide intermediate structures which capture the principal features of the manifold (surface) of interest through its ridges and valleys. As landmarks are often available these are used as anchoring points, but surface curvature information is the principal guide in estimating the curve locations. The surface patches between these curves are relatively flat and can be represented in a standardised manner by appropriate surface transects to give a complete surface model. This new approach does not require the use of a template, reference sample or any external information to guide the method and, when compared with a surface based approach, the estimation of curves is shown to have improved performance. In addition, examples involving applications to mussel shells and human faces show that the analysis of curve information can deliver more targeted and effective insight than the use of full surface information.

Armin Schwartzman, Andrew J. Schork, Rong Zablocki, Wesley K. Thompson.

Source: The Annals of Applied Statistics, Volume 13, Number 4, 2509--2538.

Abstract:
Analysis of genome-wide association studies (GWAS) is characterized by a large number of univariate regressions where a quantitative trait is regressed on hundreds of thousands to millions of single-nucleotide polymorphism (SNP) allele counts, one at a time. This article proposes an estimator of the SNP heritability of the trait, defined here as the fraction of the variance of the trait explained by the SNPs in the study. The proposed GWAS heritability (GWASH) estimator is easy to compute, highly interpretable and is consistent as the number of SNPs and the sample size increase. More importantly, it can be computed from summary statistics typically reported in GWAS, not requiring access to the original data. The estimator takes full account of the linkage disequilibrium (LD) or correlation between the SNPs in the study through moments of the LD matrix, estimable from auxiliary datasets. Unlike other proposed estimators in the literature, we establish the theoretical properties of the GWASH estimator and obtain analytical estimates of the precision, allowing for power and sample size calculations for SNP heritability estimates and forming a firm foundation for future methodological development.

Gianluca Mastrantonio, Clara Grazian, Sara Mancinelli, Enrico Bibbona.

Source: The Annals of Applied Statistics, Volume 13, Number 4, 2483--2508.

Abstract:
Improved communication systems, shrinking battery sizes and the price drop of tracking devices have led to an increasing availability of trajectory tracking data. These data are often analyzed to understand animal behavior. In this work, we propose a new model for interpreting the animal movent as a mixture of characteristic patterns, that we interpret as different behaviors. The probability that the animal is behaving according to a specific pattern, at each time instant, is nonparametrically estimated using the Logistic-Gaussian process. Owing to a new formalization and the way we specify the coregionalization matrix of the associated multivariate Gaussian process, our model is invariant with respect to the choice of the reference element and of the ordering of the probability vector components. We fit the model under a Bayesian framework, and show that the Markov chain Monte Carlo algorithm we propose is straightforward to implement. We perform a simulation study with the aim of showing the ability of the estimation procedure to retrieve the model parameters. We also test the performance of the information criterion we used to select the number of behaviors. The model is then applied to a real dataset where a wolf has been observed before and after procreation. The results are easy to interpret, and clear differences emerge in the two phases.

Kun Liang.

Source: The Annals of Applied Statistics, Volume 13, Number 4, 2452--2482.

Abstract:
Finding differentially expressed genes is a common task in high-throughput transcriptome studies. While traditional statistical methods rank the genes by their test statistics alone, we analyze an RNA sequencing dataset using the auxiliary information of gene length and the test statistics from a related microarray study. Given the auxiliary information, we propose a novel nonparametric empirical Bayes procedure to estimate the posterior probability of differential expression for each gene. We demonstrate the advantage of our procedure in extensive simulation studies and a psoriasis RNA sequencing study. The companion R package calm is available at Bioconductor.

Dale L. Zimmerman, Jun Tang, Rui Huang.

Source: The Annals of Applied Statistics, Volume 13, Number 4, 2416--2451.

Abstract:
We extend statistical shape analytic methods known as outline analysis for application to the strike zone, a central feature of the game of baseball. Although the strike zone is rigorously defined by Major League Baseball’s official rules, umpires make mistakes in calling pitches as strikes (and balls) and may even adhere to a strike zone somewhat different than that prescribed by the rule book. Our methods yield inference on geometric attributes (centroid, dimensions, orientation and shape) of this “called strike zone” (CSZ) and on the effects that years, umpires, player attributes, game situation factors and their interactions have on those attributes. The methodology consists of first using kernel discriminant analysis to determine a noisy outline representing the CSZ corresponding to each factor combination, then fitting existing elliptic Fourier and new generalized superelliptic models for closed curves to that outline and finally analyzing the fitted model coefficients using standard methods of regression analysis, factorial analysis of variance and variance component estimation. We apply these methods to PITCHf/x data comprising more than three million called pitches from the 2008–2016 Major League Baseball seasons to address numerous questions about the CSZ. We find that all geometric attributes of the CSZ, except its size, became significantly more like those of the rule-book strike zone from 2008–2016 and that several player attribute/game situation factors had statistically and practically significant effects on many of them. We also establish that the variation in the horizontal center, width and area of an individual umpire’s CSZ from pitch to pitch is smaller than their variation among CSZs from different umpires.

Fan Li, Fan Li.

Source: The Annals of Applied Statistics, Volume 13, Number 4, 2389--2415.

Abstract:
Causal or unconfounded descriptive comparisons between multiple groups are common in observational studies. Motivated from a racial disparity study in health services research, we propose a unified propensity score weighting framework, the balancing weights, for estimating causal effects with multiple treatments. These weights incorporate the generalized propensity scores to balance the weighted covariate distribution of each treatment group, all weighted toward a common prespecified target population. The class of balancing weights include several existing approaches such as the inverse probability weights and trimming weights as special cases. Within this framework, we propose a set of target estimands based on linear contrasts. We further develop the generalized overlap weights, constructed as the product of the inverse probability weights and the harmonic mean of the generalized propensity scores. The generalized overlap weighting scheme corresponds to the target population with the most overlap in covariates across the multiple treatments. These weights are bounded and thus bypass the problem of extreme propensities. We show that the generalized overlap weights minimize the total asymptotic variance of the moment weighting estimators for the pairwise contrasts within the class of balancing weights. We consider two balance check criteria and propose a new sandwich variance estimator for estimating the causal effects with generalized overlap weights. We apply these methods to study the racial disparities in medical expenditure between several racial groups using the 2009 Medical Expenditure Panel Survey (MEPS) data. Simulations were carried out to compare with existing methods.

John R. Tipton, Mevin B. Hooten, Connor Nolan, Robert K. Booth, Jason McLachlan.

Source: The Annals of Applied Statistics, Volume 13, Number 4, 2363--2388.

Abstract:
Multivariate compositional count data arise in many applications including ecology, microbiology, genetics and paleoclimate. A frequent question in the analysis of multivariate compositional count data is what underlying values of a covariate(s) give rise to the observed composition. Learning the relationship between covariates and the compositional count allows for inverse prediction of unobserved covariates given compositional count observations. Gaussian processes provide a flexible framework for modeling functional responses with respect to a covariate without assuming a functional form. Many scientific disciplines use Gaussian process approximations to improve prediction and make inference on latent processes and parameters. When prediction is desired on unobserved covariates given realizations of the response variable, this is called inverse prediction. Because inverse prediction is often mathematically and computationally challenging, predicting unobserved covariates often requires fitting models that are different from the hypothesized generative model. We present a novel computational framework that allows for efficient inverse prediction using a Gaussian process approximation to generative models. Our framework enables scientific learning about how the latent processes co-vary with respect to covariates while simultaneously providing predictions of missing covariates. The proposed framework is capable of efficiently exploring the high dimensional, multi-modal latent spaces that arise in the inverse problem. To demonstrate flexibility, we apply our method in a generalized linear model framework to predict latent climate states given multivariate count data. Based on cross-validation, our model has predictive skill competitive with current methods while simultaneously providing formal, statistical inference on the underlying community dynamics of the biological system previously not available.

Susheela P. Singh, Ana-Maria Staicu, Robert R. Dunn, Noah Fierer, Brian J. Reich.

Source: The Annals of Applied Statistics, Volume 13, Number 4, 2341--2362.

Abstract:
The advent of high-throughput sequencing technologies has made data from DNA material readily available, leading to a surge of microbiome-related research establishing links between markers of microbiome health and specific outcomes. However, to harness the power of microbial communities we must understand not only how they affect us, but also how they can be influenced to improve outcomes. This area has been dominated by methods that reduce community composition to summary metrics, which can fail to fully exploit the complexity of community data. Recently, methods have been developed to model the abundance of taxa in a community, but they can be computationally intensive and do not account for spatial effects underlying microbial settlement. These spatial effects are particularly relevant in the microbiome setting because we expect communities that are close together to be more similar than those that are far apart. In this paper, we propose a flexible Bayesian spike-and-slab variable selection model for presence-absence indicators that accounts for spatial dependence and cross-dependence between taxa while reducing dimensionality in both directions. We show by simulation that in the presence of spatial dependence, popular distance-based hypothesis testing methods fail to preserve their advertised size, and the proposed method improves variable selection. Finally, we present an application of our method to an indoor fungal community found within homes across the contiguous United States.

Stephen Berg, Jun Zhu, Murray K. Clayton, Monika E. Shea, David J. Mladenoff.

Source: The Annals of Applied Statistics, Volume 13, Number 4, 2312--2340.

Abstract:
The Wisconsin Public Land Survey database describes historical forest composition at high spatial resolution and is of interest in ecological studies of forest composition in Wisconsin just prior to significant Euro-American settlement. For such studies it is useful to identify recurring subpopulations of tree species known as communities, but standard clustering approaches for subpopulation identification do not account for dependence between spatially nearby observations. Here, we develop and fit a latent discrete Markov random field model for the purpose of identifying and classifying historical forest communities based on spatially referenced multivariate tree species counts across Wisconsin. We show empirically for the actual dataset and through simulation that our latent Markov random field modeling approach improves prediction and parameter estimation performance. For model fitting we introduce a new stochastic approximation algorithm which enables computationally efficient estimation and classification of large amounts of spatial multivariate count data.

Federico Castelletti, Guido Consonni.

Source: The Annals of Applied Statistics, Volume 13, Number 4, 2289--2311.

Abstract:
A signalling pathway is a sequence of chemical reactions initiated by a stimulus which in turn affects a receptor, and then through some intermediate steps cascades down to the final cell response. Based on the technique of flow cytometry, samples of cell-by-cell measurements are collected under each experimental condition, resulting in a collection of interventional data (assuming no latent variables are involved). Usually several external interventions are applied at different points of the pathway, the ultimate aim being the structural recovery of the underlying signalling network which we model as a causal Directed Acyclic Graph (DAG) using intervention calculus. The advantage of using interventional data, rather than purely observational one, is that identifiability of the true data generating DAG is enhanced. More technically a Markov equivalence class of DAGs, whose members are statistically indistinguishable based on observational data alone, can be further decomposed, using additional interventional data, into smaller distinct Interventional Markov equivalence classes. We present a Bayesian methodology for structural learning of Interventional Markov equivalence classes based on observational and interventional samples of multivariate Gaussian observations. Our approach is objective, meaning that it is based on default parameter priors requiring no personal elicitation; some flexibility is however allowed through a tuning parameter which regulates sparsity in the prior on model space. Based on an analytical expression for the marginal likelihood of a given Interventional Essential Graph, and a suitable MCMC scheme, our analysis produces an approximate posterior distribution on the space of Interventional Markov equivalence classes, which can be used to provide uncertainty quantification for features of substantive scientific interest, such as the posterior probability of inclusion of selected edges, or paths.

Ningshan Zhang, Kyle Schmaus, Patrick O. Perry.

Source: The Annals of Applied Statistics, Volume 13, Number 4, 2260--2288.

Abstract:
We consider a particular instance of a common problem in recommender systems, using a database of book reviews to inform user-targeted recommendations. In our dataset, books are categorized into genres and subgenres. To exploit this nested taxonomy, we use a hierarchical model that enables information pooling across across similar items at many levels within the genre hierarchy. The main challenge in deploying this model is computational. The data sizes are large and fitting the model at scale using off-the-shelf maximum likelihood procedures is prohibitive. To get around this computational bottleneck, we extend a moment-based fitting procedure proposed for fitting single-level hierarchical models to the general case of arbitrarily deep hierarchies. This extension is an order of magnitude faster than standard maximum likelihood procedures. The fitting method can be deployed beyond recommender systems to general contexts with deeply nested hierarchical generalized linear mixed models.

Cecilia Balocchi, Shane T. Jensen.

Source: The Annals of Applied Statistics, Volume 13, Number 4, 2235--2259.

Abstract:
Understanding the relationship between change in crime over time and the geography of urban areas is an important problem for urban planning. Accurate estimation of changing crime rates throughout a city would aid law enforcement as well as enable studies of the association between crime and the built environment. Bayesian modeling is a promising direction since areal data require principled sharing of information to address spatial autocorrelation between proximal neighborhoods. We develop several Bayesian approaches to spatial sharing of information between neighborhoods while modeling trends in crime counts over time. We apply our methodology to estimate changes in crime throughout Philadelphia over the 2006-15 period while also incorporating spatially-varying economic and demographic predictors. We find that the local shrinkage imposed by a conditional autoregressive model has substantial benefits in terms of out-of-sample predictive accuracy of crime. We also explore the possibility of spatial discontinuities between neighborhoods that could represent natural barriers or aspects of the built environment.

Ian L. Dryden, Kwang-Rae Kim, Charles A. Laughton, Huiling Le.

Source: The Annals of Applied Statistics, Volume 13, Number 4, 2213--2234.

Abstract:
Molecular dynamics simulations produce huge datasets of temporal sequences of molecules. It is of interest to summarize the shape evolution of the molecules in a succinct, low-dimensional representation. However, Euclidean techniques such as principal components analysis (PCA) can be problematic as the data may lie far from in a flat manifold. Principal nested spheres gives a fundamentally different decomposition of data from the usual Euclidean subspace based PCA [ Biometrika 99 (2012) 551–568]. Subspaces of successively lower dimension are fitted to the data in a backwards manner with the aim of retaining signal and dispensing with noise at each stage. We adapt the methodology to 3D subshape spaces and provide some practical fitting algorithms. The methodology is applied to cluster analysis of peptides, where different states of the molecules can be identified. Also, the temporal transitions between cluster states are explored.

Carolyn M. Rutter, Jonathan Ozik, Maria DeYoreo, Nicholson Collier.

Source: The Annals of Applied Statistics, Volume 13, Number 4, 2189--2212.

Abstract:
Microsimulation models (MSMs) are used to inform policy by predicting population-level outcomes under different scenarios. MSMs simulate individual-level event histories that mark the disease process (such as the development of cancer) and the effect of policy actions (such as screening) on these events. MSMs often have many unknown parameters; calibration is the process of searching the parameter space to select parameters that result in accurate MSM prediction of a wide range of targets. We develop Incremental Mixture Approximate Bayesian Computation (IMABC) for MSM calibration which results in a simulated sample from the posterior distribution of model parameters given calibration targets. IMABC begins with a rejection-based ABC step, drawing a sample of points from the prior distribution of model parameters and accepting points that result in simulated targets that are near observed targets. Next, the sample is iteratively updated by drawing additional points from a mixture of multivariate normal distributions and accepting points that result in accurate predictions. Posterior estimates are obtained by weighting the final set of accepted points to account for the adaptive sampling scheme. We demonstrate IMABC by calibrating CRC-SPIN 2.0, an updated version of a MSM for colorectal cancer (CRC) that has been used to inform national CRC screening guidelines.

Emily Berg, Danhyang Lee.

Source: The Annals of Applied Statistics, Volume 13, Number 4, 2158--2188.

Abstract:
Quantiles of the distributions of several measures of erosion are important parameters in the Conservation Effects Assessment Project, a survey intended to quantify soil and nutrient loss on crop fields. Because sample sizes for domains of interest are too small to support reliable direct estimators, model based methods are needed. Quantile regression is appealing for CEAP because finding a single family of parametric models that adequately describes the distributions of all variables is difficult and small area quantiles are parameters of interest. We construct empirical Bayes predictors and bootstrap mean squared error estimators based on the linearly interpolated generalized Pareto distribution (LIGPD). We apply the procedures to predict county-level quantiles for four types of erosion in Wisconsin and validate the procedures through simulation.

Hongbin Zhang, Lang Wu.

Source: The Annals of Applied Statistics, Volume 13, Number 4, 2140--2157.

Abstract:
For a time-to-event outcome with censored time-varying covariates, a joint Cox model with a linear mixed effects model is the standard modeling approach. In some applications such as AIDS studies, mechanistic nonlinear models are available for some covariate process such as viral load during anti-HIV treatments, derived from the underlying data-generation mechanisms and disease progression. Such a mechanistic nonlinear covariate model may provide better-predicted values when the covariates are left censored or mismeasured. When the focus is on the impact of the time-varying covariate process on the survival outcome, an accelerated failure time (AFT) model provides an excellent alternative to the Cox proportional hazard model since an AFT model is formulated to allow the influence of the outcome by the entire covariate process. In this article, we consider a nonlinear mixed effects model for the censored covariates in an AFT model, implemented using a Monte Carlo EM algorithm, under the framework of a joint model for simultaneous inference. We apply the joint model to an HIV/AIDS data to gain insights for assessing the association between viral load and immunological restoration during antiretroviral therapy. Simulation is conducted to compare model performance when the covariate model and the survival model are misspecified.

Jose Ameijeiras-Alonso, Akli Benali, Rosa M. Crujeiras, Alberto Rodríguez-Casal, José M. C. Pereira.

Source: The Annals of Applied Statistics, Volume 13, Number 4, 2120--2139.

Abstract:
Understanding the role of vegetation fires in the Earth system is an important environmental problem. Although fire occurrence is influenced by natural factors, human activity related to land use and management has altered the temporal patterns of fire in several regions of the world. Hence, for a better insight into fires regimes it is of special interest to analyze where human activity has altered fire seasonality. For doing so, multimodality tests are a useful tool for determining the number of annual fire peaks. The periodicity of fires and their complex distributional features motivate the use of nonparametric circular statistics. The unsatisfactory performance of previous circular nonparametric proposals for testing multimodality justifies the introduction of a new approach, considering an adapted version of the excess mass statistic, jointly with a bootstrap calibration algorithm. A systematic application of the test on the Russia–Kazakhstan area is presented in order to determine how many fire peaks can be identified in this region. A False Discovery Rate correction, accounting for the spatial dependence of the data, is also required.

Jason Xu, Samson Koelle, Peter Guttorp, Chuanfeng Wu, Cynthia Dunbar, Janis L. Abkowitz, Vladimir N. Minin.

Source: The Annals of Applied Statistics, Volume 13, Number 4, 2091--2119.

Abstract:
Single-cell lineage tracking strategies enabled by recent experimental technologies have produced significant insights into cell fate decisions, but lack the quantitative framework necessary for rigorous statistical analysis of mechanistic models describing cell division and differentiation. In this paper, we develop such a framework with corresponding moment-based parameter estimation techniques for continuous-time, multi-type branching processes. Such processes provide a probabilistic model of how cells divide and differentiate, and we apply our method to study hematopoiesis , the mechanism of blood cell production. We derive closed-form expressions for higher moments in a general class of such models. These analytical results allow us to efficiently estimate parameters of much richer statistical models of hematopoiesis than those used in previous statistical studies. To our knowledge, the method provides the first rate inference procedure for fitting such models to time series data generated from cellular barcoding experiments. After validating the methodology in simulation studies, we apply our estimator to hematopoietic lineage tracking data from rhesus macaques. Our analysis provides a more complete understanding of cell fate decisions during hematopoiesis in nonhuman primates, which may be more relevant to human biology and clinical strategies than previous findings from murine studies. For example, in addition to previously estimated hematopoietic stem cell self-renewal rate, we are able to estimate fate decision probabilities and to compare structurally distinct models of hematopoiesis using cross validation. These estimates of fate decision probabilities and our model selection results should help biologists compare competing hypotheses about how progenitor cells differentiate. The methodology is transferrable to a large class of stochastic compartmental and multi-type branching models, commonly used in studies of cancer progression, epidemiology and many other fields.

Gabriela V. Cohen Freue, David Kepplinger, Matías Salibián-Barrera, Ezequiel Smucler.

Source: The Annals of Applied Statistics, Volume 13, Number 4, 2065--2090.

Abstract:
In large-scale quantitative proteomic studies, scientists measure the abundance of thousands of proteins from the human proteome in search of novel biomarkers for a given disease. Penalized regression estimators can be used to identify potential biomarkers among a large set of molecular features measured. Yet, the performance and statistical properties of these estimators depend on the loss and penalty functions used to define them. Motivated by a real plasma proteomic biomarkers study, we propose a new class of penalized robust estimators based on the elastic net penalty, which can be tuned to keep groups of correlated variables together in the selected model and maintain robustness against possible outliers. We also propose an efficient algorithm to compute our robust penalized estimators and derive a data-driven method to select the penalty term. Our robust penalized estimators have very good robustness properties and are also consistent under certain regularity conditions. Numerical results show that our robust estimators compare favorably to other robust penalized estimators. Using our proposed methodology for the analysis of the proteomics data, we identify new potentially relevant biomarkers of cardiac allograft vasculopathy that are not found with nonrobust alternatives. The selected model is validated in a new set of 52 test samples and achieves an area under the receiver operating characteristic (AUC) of 0.85.

Hannah Worthington, Rachel McCrea, Ruth King, Richard Griffiths.

Source: The Annals of Applied Statistics, Volume 13, Number 4, 2043--2064.

Abstract:
Capture-recapture studies often involve collecting data on numerous capture occasions over a relatively short period of time. For many study species this process is repeated, for example, annually, resulting in capture information spanning multiple sampling periods. To account for the different temporal scales, the robust design class of models have traditionally been applied providing a framework in which to analyse all of the available capture data in a single likelihood expression. However, these models typically require strong constraints, either the assumption of closure within a sampling period (the closed robust design) or conditioning on the number of individuals captured within a sampling period (the open robust design). For real datasets these assumptions may not be appropriate. We develop a general modelling structure that requires neither assumption by explicitly modelling the movement of individuals into the population both within and between the sampling periods, which in turn permits the estimation of abundance within a single consistent framework. The flexibility of the novel model structure is further demonstrated by including the computationally challenging case of multi-state data where there is individual time-varying discrete covariate information. We derive an efficient likelihood expression for the new multi-state multi-period stopover model using the hidden Markov model framework. We demonstrate the significant improvement in parameter estimation using our new modelling approach in terms of both the multi-period and multi-state components through both a simulation study and a real dataset relating to the protected species of great crested newts, Triturus cristatus .

Ye Zhang, Zhigang Yao, Patrik Forssén, Torgny Fornstedt.

Source: The Annals of Applied Statistics, Volume 13, Number 4, 2011--2042.

Abstract:
The means to obtain the rate constants of a chemical reaction is a fundamental open problem in both science and the industry. Traditional techniques for finding rate constants require either chemical modifications of the reactants or indirect measurements. The rate constant map method is a modern technique to study binding equilibrium and kinetics in chemical reactions. Finding a rate constant map from biosensor data is an ill-posed inverse problem that is usually solved by regularization. In this work, rather than finding a deterministic regularized rate constant map that does not provide uncertainty quantification of the solution, we develop an adaptive variational Bayesian approach to estimate the distribution of the rate constant map, from which some intrinsic properties of a chemical reaction can be explored, including information about rate constants. Our new approach is more realistic than the existing approaches used for biosensors and allows us to estimate the dynamics of the interactions, which are usually hidden in a deterministic approximate solution. We verify the performance of the new proposed method by numerical simulations, and compare it with the Markov chain Monte Carlo algorithm. The results illustrate that the variational method can reliably capture the posterior distribution in a computationally efficient way. Finally, the developed method is also tested on the real biosensor data (parathyroid hormone), where we provide two novel analysis tools—the thresholding contour map and the high order moment map—to estimate the number of interactions as well as their rate constants.

Bret Zeldow, Vincent Lo Re III, Jason Roy.

Source: The Annals of Applied Statistics, Volume 13, Number 3, 1989--2010.

Abstract:
Bayesian Additive Regression Trees (BART) is a flexible machine learning algorithm capable of capturing nonlinearities between an outcome and covariates and interactions among covariates. We extend BART to a semiparametric regression framework in which the conditional expectation of an outcome is a function of treatment, its effect modifiers, and confounders. The confounders are allowed to have unspecified functional form, while treatment and effect modifiers that are directly related to the research question are given a linear form. The result is a Bayesian semiparametric linear regression model where the posterior distribution of the parameters of the linear part can be interpreted as in parametric Bayesian regression. This is useful in situations where a subset of the variables are of substantive interest and the others are nuisance variables that we would like to control for. An example of this occurs in causal modeling with the structural mean model (SMM). Under certain causal assumptions, our method can be used as a Bayesian SMM. Our methods are demonstrated with simulation studies and an application to dataset involving adults with HIV/Hepatitis C coinfection who newly initiate antiretroviral therapy. The methods are available in an R package called semibart.

Youyi Zhang, Jeffrey S. Morris, Shivali Narang Aerry, Arvind U. K. Rao, Veerabhadran Baladandayuthapani.

Source: The Annals of Applied Statistics, Volume 13, Number 3, 1957--1988.

Abstract:
Technological innovations have produced large multi-modal datasets that include imaging and multi-platform genomics data. Integrative analyses of such data have the potential to reveal important biological and clinical insights into complex diseases like cancer. In this paper, we present Bayesian approaches for integrative analysis of radiological imaging and multi-platform genomic data, where-in our goals are to simultaneously identify genomic and radiomic, that is, radiology-based imaging markers, along with the latent associations between these two modalities, and to detect the overall prognostic relevance of the combined markers. For this task, we propose Radio-iBAG: Radiomics-based Integrative Bayesian Analysis of Multiplatform Genomic Data , a multi-scale Bayesian hierarchical model that involves several innovative strategies: it incorporates integrative analysis of multi-platform genomic data sets to capture fundamental biological relationships; explores the associations between radiomic markers accompanying genomic information with clinical outcomes; and detects genomic and radiomic markers associated with clinical prognosis. We also introduce the use of sparse Principal Component Analysis (sPCA) to extract a sparse set of approximately orthogonal meta-features each containing information from a set of related individual radiomic features, reducing dimensionality and combining like features. Our methods are motivated by and applied to The Cancer Genome Atlas glioblastoma multiforme data set, where-in we integrate magnetic resonance imaging-based biomarkers along with genomic, epigenomic and transcriptomic data. Our model identifies important magnetic resonance imaging features and the associated genomic platforms that are related with patient survival times.

Chanmin Kim, Michael J. Daniels, Joseph W. Hogan, Christine Choirat, Corwin M. Zigler.

Source: The Annals of Applied Statistics, Volume 13, Number 3, 1927--1956.

Abstract:
Emission control technologies installed on power plants are a key feature of many air pollution regulations in the US. While such regulations are predicated on the presumed relationships between emissions, ambient air pollution and human health, many of these relationships have never been empirically verified. The goal of this paper is to develop new statistical methods to quantify these relationships. We frame this problem as one of mediation analysis to evaluate the extent to which the effect of a particular control technology on ambient pollution is mediated through causal effects on power plant emissions. Since power plants emit various compounds that contribute to ambient pollution, we develop new methods for multiple intermediate variables that are measured contemporaneously, may interact with one another, and may exhibit joint mediating effects. Specifically, we propose new methods leveraging two related frameworks for causal inference in the presence of mediating variables: principal stratification and causal mediation analysis. We define principal effects based on multiple mediators, and also introduce a new decomposition of the total effect of an intervention on ambient pollution into the natural direct effect and natural indirect effects for all combinations of mediators. Both approaches are anchored to the same observed-data models, which we specify with Bayesian nonparametric techniques. We provide assumptions for estimating principal causal effects, then augment these with an additional assumption required for causal mediation analysis. The two analyses, interpreted in tandem, provide the first empirical investigation of the presumed causal pathways that motivate important air quality regulatory policies.

Jeffrey Regier, Andrew C. Miller, David Schlegel, Ryan P. Adams, Jon D. McAuliffe, Prabhat.

Source: The Annals of Applied Statistics, Volume 13, Number 3, 1884--1926.

Abstract:
We present a new, fully generative model for constructing astronomical catalogs from optical telescope image sets. Each pixel intensity is treated as a random variable with parameters that depend on the latent properties of stars and galaxies. These latent properties are themselves modeled as random. We compare two procedures for posterior inference. One procedure is based on Markov chain Monte Carlo (MCMC) while the other is based on variational inference (VI). The MCMC procedure excels at quantifying uncertainty, while the VI procedure is 1000 times faster. On a supercomputer, the VI procedure efficiently uses 665,000 CPU cores to construct an astronomical catalog from 50 terabytes of images in 14.6 minutes, demonstrating the scaling characteristics necessary to construct catalogs for upcoming astronomical surveys.

Byron C. Jaeger, D. Leann Long, Dustin M. Long, Mario Sims, Jeff M. Szychowski, Yuan-I Min, Leslie A. Mcclure, George Howard, Noah Simon.

Source: The Annals of Applied Statistics, Volume 13, Number 3, 1847--1883.

Abstract:
We introduce and evaluate the oblique random survival forest (ORSF). The ORSF is an ensemble method for right-censored survival data that uses linear combinations of input variables to recursively partition a set of training data. Regularized Cox proportional hazard models are used to identify linear combinations of input variables in each recursive partitioning step. Benchmark results using simulated and real data indicate that the ORSF’s predicted risk function has high prognostic value in comparison to random survival forests, conditional inference forests, regression and boosting. In an application to data from the Jackson Heart Study, we demonstrate variable and partial dependence using the ORSF and highlight characteristics of its ten-year predicted risk function for atherosclerotic cardiovascular disease events (ASCVD; stroke, coronary heart disease). We present visualizations comparing variable and partial effect estimation according to the ORSF, the conditional inference forest, and the Pooled Cohort Risk equations. The obliqueRSF R package, which provides functions to fit the ORSF and create variable and partial dependence plots, is available on the comprehensive R archive network (CRAN).

Jessica K. Hargreaves, Marina I. Knight, Jon W. Pitchford, Rachael J. Oakenfull, Sangeeta Chawla, Jack Munns, Seth J. Davis.

Source: The Annals of Applied Statistics, Volume 13, Number 3, 1817--1846.

Abstract:
Rhythmic data are ubiquitous in the life sciences. Biologists need reliable statistical tests to identify whether a particular experimental treatment has caused a significant change in a rhythmic signal. When these signals display nonstationary behaviour, as is common in many biological systems, the established methodologies may be misleading. Therefore, there is a real need for new methodology that enables the formal comparison of nonstationary processes. As circadian behaviour is best understood in the spectral domain, here we develop novel hypothesis testing procedures in the (wavelet) spectral domain, embedding replicate information when available. The data are modelled as realisations of locally stationary wavelet processes, allowing us to define and rigorously estimate their evolutionary wavelet spectra. Motivated by three complementary applications in circadian biology, our new methodology allows the identification of three specific types of spectral difference. We demonstrate the advantages of our methodology over alternative approaches, by means of a comprehensive simulation study and real data applications, using both published and newly generated circadian datasets. In contrast to the current standard methodologies, our method successfully identifies differences within the motivating circadian datasets, and facilitates wider ranging analyses of rhythmic biological data in general.

Arkaprava Roy, Subhashis Ghosal, Jeffrey Prescott, Kingshuk Roy Choudhury.

Source: The Annals of Applied Statistics, Volume 13, Number 3, 1791--1816.

Abstract:
We study possible relations between Alzheimer’s disease progression and the structure of the connectome which is white matter connecting different regions of the brain. Regression models in covariates including age, gender and disease status for the extent of white matter connecting each pair of regions of the brain are proposed. Subject inhomogeneity is also incorporated in the model through random effects with an unknown distribution. As there is a large number of pairs of regions, we also adopt a dimension reduction technique through graphon ( J. Combin. Theory Ser. B 96 (2006) 933–957) functions which reduces the functions of pairs of regions to functions of regions. The connecting graphon functions are considered unknown but the assumed smoothness allows putting priors of low complexity on these functions. We pursue a nonparametric Bayesian approach by assigning a Dirichlet process scale mixture of zero to mean normal prior on the distributions of the random effects and finite random series of tensor products of B-splines priors on the underlying graphon functions. We develop efficient Markov chain Monte Carlo techniques for drawing samples for the posterior distributions using Hamiltonian Monte Carlo (HMC). The proposed Bayesian method overwhelmingly outperforms a competing method based on ANCOVA models in the simulation setup. The proposed Bayesian approach is applied on a dataset of 100 subjects and 83 brain regions and key regions implicated in the changing connectome are identified.