Alex Diana, Eleni Matechou, Jim Griffin, Alison Johnston.

Source: The Annals of Applied Statistics, Volume 14, Number 1, 473--493.

Abstract:
Environmental changes in recent years have been linked to phenological shifts which in turn are linked to the survival of species. The work in this paper is motivated by capture-recapture data on blackcaps collected by the British Trust for Ornithology as part of the Constant Effort Sites monitoring scheme. Blackcaps overwinter abroad and migrate to the UK annually for breeding purposes. We propose a novel Bayesian nonparametric approach for expressing the bivariate density of individual arrival and departure times at different sites across a number of years as a mixture model. The new model combines the ideas of the hierarchical and the dependent Dirichlet process, allowing the estimation of site-specific weights and year-specific mixture locations, which are modelled as functions of environmental covariates using a multivariate extension of the Gaussian process. The proposed modelling framework is extremely general and can be used in any context where multivariate density estimation is performed jointly across different groups and in the presence of a continuous covariate.

Yicheng Li, Adrian E. Raftery.

Source: The Annals of Applied Statistics, Volume 14, Number 1, 381--408.

Abstract:
Smoking is one of the leading preventable threats to human health and a major risk factor for lung cancer, upper aerodigestive cancer and chronic obstructive pulmonary disease. Estimating and forecasting the smoking attributable fraction (SAF) of mortality can yield insights into smoking epidemics and also provide a basis for more accurate mortality and life expectancy projection. Peto et al. ( Lancet 339 (1992) 1268–1278) proposed a method to estimate the SAF using the lung cancer mortality rate as an indicator of exposure to smoking in the population of interest. Here, we use the same method to estimate the all-age SAF (ASAF) for both genders for over 60 countries. We document a strong and cross-nationally consistent pattern of the evolution of the SAF over time. We use this as the basis for a new Bayesian hierarchical model to project future male and female ASAF from over 60 countries simultaneously. This gives forecasts as well as predictive distributions that can be used to find uncertainty intervals for any quantity of interest. We assess the model using out-of-sample predictive validation and find that it provides good forecasts and well-calibrated forecast intervals, comparing favorably with other methods.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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).

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.

Huiping Xu, Xiaochun Li, Changyu Shen, Siu L. Hui, Shaun Grannis.

Source: The Annals of Applied Statistics, Volume 13, Number 3, 1753--1790.

Abstract:
The conditional independence assumption of the Felligi and Sunter (FS) model in probabilistic record linkage is often violated when matching real-world data. Ignoring conditional dependence has been shown to seriously bias parameter estimates. However, in record linkage, the ultimate goal is to inform the match status of record pairs and therefore, record linkage algorithms should be evaluated in terms of matching accuracy. In the literature, more flexible models have been proposed to relax the conditional independence assumption, but few studies have assessed whether such accommodations improve matching accuracy. In this paper, we show that incorporating the conditional dependence appropriately yields comparable or improved matching accuracy than the FS model using three real-world data linkage examples. Through a simulation study, we further investigate when conditional dependence models provide improved matching accuracy. Our study shows that the FS model is generally robust to the conditional independence assumption and provides comparable matching accuracy as the more complex conditional dependence models. However, when the match prevalence approaches 0% or 100% and conditional dependence exists in the dominating class, it is necessary to address conditional dependence as the FS model produces suboptimal matching accuracy. The need to address conditional dependence becomes less important when highly discriminating fields are used. Our simulation study also shows that conditional dependence models with misspecified dependence structure could produce less accurate record matching than the FS model and therefore we caution against the blind use of conditional dependence models.

Yiyi Liu, Joshua L. Warren, Hongyu Zhao.

Source: The Annals of Applied Statistics, Volume 13, Number 3, 1733--1752.

Abstract:
Understanding the heterogeneity of cells is an important biological question. The development of single-cell RNA-sequencing (scRNA-seq) technology provides high resolution data for such inquiry. A key challenge in scRNA-seq analysis is the high variability of measured RNA expression levels and frequent dropouts (missing values) due to limited input RNA compared to bulk RNA-seq measurement. Existing clustering methods do not perform well for these noisy and zero-inflated scRNA-seq data. In this manuscript we propose a Bayesian hierarchical model, called BasClu, to appropriately characterize important features of scRNA-seq data in order to more accurately cluster cells. We demonstrate the effectiveness of our method with extensive simulation studies and applications to three real scRNA-seq datasets.

Qiwei Li, Xinlei Wang, Faming Liang, Guanghua Xiao.

Source: The Annals of Applied Statistics, Volume 13, Number 3, 1708--1732.

Abstract:
With the advance of imaging technology, digital pathology imaging of tumor tissue slides is becoming a routine clinical procedure for cancer diagnosis. This process produces massive imaging data that capture histological details in high resolution. Recent developments in deep-learning methods have enabled us to identify and classify individual cells from digital pathology images at large scale. Reliable statistical approaches to model the spatial pattern of cells can provide new insight into tumor progression and shed light on the biological mechanisms of cancer. We consider the problem of modeling spatial correlations among three commonly seen cells observed in tumor pathology images. A novel geostatistical marking model with interpretable underlying parameters is proposed in a Bayesian framework. We use auxiliary variable MCMC algorithms to sample from the posterior distribution with an intractable normalizing constant. We demonstrate how this model-based analysis can lead to sharper inferences than ordinary exploratory analyses, by means of application to three benchmark datasets and a case study on the pathology images of $188$ lung cancer patients. The case study shows that the spatial correlation between tumor and stromal cells predicts patient prognosis. This statistical methodology not only presents a new model for characterizing spatial correlations in a multitype spatial point pattern conditioning on the locations of the points, but also provides a new perspective for understanding the role of cell–cell interactions in cancer progression.

Seong-Hwan Jun, Samuel W. K. Wong, James V. Zidek, Alexandre Bouchard-Côté.

Source: The Annals of Applied Statistics, Volume 13, Number 3, 1678--1707.

Abstract:
In this paper, we consider the knot-matching problem arising in computational forestry. The knot-matching problem is an important problem that needs to be solved to advance the state of the art in automatic strength prediction of lumber. We show that this problem can be formulated as a quadripartite matching problem and develop a sequential decision model that admits efficient parameter estimation along with a sequential Monte Carlo sampler on graph matching that can be utilized for rapid sampling of graph matching. We demonstrate the effectiveness of our methods on 30 manually annotated boards and present findings from various simulation studies to provide further evidence supporting the efficacy of our methods.

Jesús D. Arroyo Relión, Daniel Kessler, Elizaveta Levina, Stephan F. Taylor.

Source: The Annals of Applied Statistics, Volume 13, Number 3, 1648--1677.

Abstract:
While statistical analysis of a single network has received a lot of attention in recent years, with a focus on social networks, analysis of a sample of networks presents its own challenges which require a different set of analytic tools. Here we study the problem of classification of networks with labeled nodes, motivated by applications in neuroimaging. Brain networks are constructed from imaging data to represent functional connectivity between regions of the brain, and previous work has shown the potential of such networks to distinguish between various brain disorders, giving rise to a network classification problem. Existing approaches tend to either treat all edge weights as a long vector, ignoring the network structure, or focus on graph topology as represented by summary measures while ignoring the edge weights. Our goal is to design a classification method that uses both the individual edge information and the network structure of the data in a computationally efficient way, and that can produce a parsimonious and interpretable representation of differences in brain connectivity patterns between classes. We propose a graph classification method that uses edge weights as predictors but incorporates the network nature of the data via penalties that promote sparsity in the number of nodes, in addition to the usual sparsity penalties that encourage selection of edges. We implement the method via efficient convex optimization and provide a detailed analysis of data from two fMRI studies of schizophrenia.

Gaoxiang Jia, Xinlei Wang, Qiwei Li, Wei Lu, Ximing Tang, Ignacio Wistuba, Yang Xie.

Source: The Annals of Applied Statistics, Volume 13, Number 3, 1617--1647.

Abstract:
Formalin-fixed paraffin-embedded (FFPE) samples have great potential for biomarker discovery, retrospective studies and diagnosis or prognosis of diseases. Their application, however, is hindered by the unsatisfactory performance of traditional gene expression profiling techniques on damaged RNAs. NanoString nCounter platform is well suited for profiling of FFPE samples and measures gene expression with high sensitivity which may greatly facilitate realization of scientific and clinical values of FFPE samples. However, methodological development for normalization, a critical step when analyzing this type of data, is far behind. Existing methods designed for the platform use information from different types of internal controls separately and rely on an overly-simplified assumption that expression of housekeeping genes is constant across samples for global scaling. Thus, these methods are not optimized for the nCounter system, not mentioning that they were not developed for FFPE samples. We construct an integrated system of random-coefficient hierarchical regression models to capture main patterns and characteristics observed from NanoString data of FFPE samples and develop a Bayesian approach to estimate parameters and normalize gene expression across samples. Our method, labeled RCRnorm, incorporates information from all aspects of the experimental design and simultaneously removes biases from various sources. It eliminates the unrealistic assumption on housekeeping genes and offers great interpretability. Furthermore, it is applicable to freshly frozen or like samples that can be generally viewed as a reduced case of FFPE samples. Simulation and applications showed the superior performance of RCRnorm.

Ying Chen, J. S. Marron, Jiejie Zhang.

Source: The Annals of Applied Statistics, Volume 13, Number 3, 1590--1616.

Abstract:
Electricity prices are high dimensional, serially dependent and have seasonal variations. We propose a Warping Functional AutoRegressive (WFAR) model that simultaneously accounts for the cross time-dependence and seasonal variations of the large dimensional data. In particular, electricity price curves are obtained by smoothing over the $24$ discrete hourly prices on each day. In the functional domain, seasonal phase variations are separated from level amplitude changes in a warping process with the Fisher–Rao distance metric, and the aligned (season-adjusted) electricity price curves are modeled in the functional autoregression framework. In a real application, the WFAR model provides superior out-of-sample forecast accuracy in both a normal functioning market, Nord Pool, and an extreme situation, the California market. The forecast performance as well as the relative accuracy improvement are stable for different markets and different time periods.

Lisa Schlosser, Torsten Hothorn, Reto Stauffer, Achim Zeileis.

Source: The Annals of Applied Statistics, Volume 13, Number 3, 1564--1589.

Abstract:
To obtain a probabilistic model for a dependent variable based on some set of explanatory variables, a distributional approach is often adopted where the parameters of the distribution are linked to regressors. In many classical models this only captures the location of the distribution but over the last decade there has been increasing interest in distributional regression approaches modeling all parameters including location, scale and shape. Notably, so-called nonhomogeneous Gaussian regression (NGR) models both mean and variance of a Gaussian response and is particularly popular in weather forecasting. Moreover, generalized additive models for location, scale and shape (GAMLSS) provide a framework where each distribution parameter is modeled separately capturing smooth linear or nonlinear effects. However, when variable selection is required and/or there are nonsmooth dependencies or interactions (especially unknown or of high-order), it is challenging to establish a good GAMLSS. A natural alternative in these situations would be the application of regression trees or random forests but, so far, no general distributional framework is available for these. Therefore, a framework for distributional regression trees and forests is proposed that blends regression trees and random forests with classical distributions from the GAMLSS framework as well as their censored or truncated counterparts. To illustrate these novel approaches in practice, they are employed to obtain probabilistic precipitation forecasts at numerous sites in a mountainous region (Tyrol, Austria) based on a large number of numerical weather prediction quantities. It is shown that the novel distributional regression forests automatically select variables and interactions, performing on par or often even better than GAMLSS specified either through prior meteorological knowledge or a computationally more demanding boosting approach.

Y. X. Rachel Wang, Purnamrita Sarkar, Oana Ursu, Anshul Kundaje, Peter J. Bickel.

Source: The Annals of Applied Statistics, Volume 13, Number 3, 1511--1536.

Abstract:
Chromosome conformation capture experiments such as Hi-C are used to map the three-dimensional spatial organization of genomes. One specific feature of the 3D organization is known as topologically associating domains (TADs), which are densely interacting, contiguous chromatin regions playing important roles in regulating gene expression. A few algorithms have been proposed to detect TADs. In particular, the structure of Hi-C data naturally inspires application of community detection methods. However, one of the drawbacks of community detection is that most methods take exchangeability of the nodes in the network for granted; whereas the nodes in this case, that is, the positions on the chromosomes, are not exchangeable. We propose a network model for detecting TADs using Hi-C data that takes into account this nonexchangeability. In addition, our model explicitly makes use of cell-type specific CTCF binding sites as biological covariates and can be used to identify conserved TADs across multiple cell types. The model leads to a likelihood objective that can be efficiently optimized via relaxation. We also prove that when suitably initialized, this model finds the underlying TAD structure with high probability. Using simulated data, we show the advantages of our method and the caveats of popular community detection methods, such as spectral clustering, in this application. Applying our method to real Hi-C data, we demonstrate the domains identified have desirable epigenetic features and compare them across different cell types.

Ahmed Aziz Ezzat, Mikyoung Jun, Yu Ding.

Source: The Annals of Applied Statistics, Volume 13, Number 3, 1484--1510.

Abstract:
Accurate short-term forecasts are indispensable for the integration of wind energy in power grids. On a wind farm, local wind conditions exhibit sizeable variations at a fine temporal resolution. Existing statistical models may capture the in-sample variations in wind behavior, but are often shortsighted to those occurring in the near future, that is, in the forecast horizon. The calibrated regime-switching method proposed in this paper introduces an action of regime dependent calibration on the predictand (here the wind speed variable), which helps correct the bias resulting from out-of-sample variations in wind behavior. This is achieved by modeling the calibration as a function of two elements: the wind regime at the time of the forecast (and the calibration is therefore regime dependent), and the runlength, which is the time elapsed since the last observed regime change. In addition to regime-switching dynamics, the proposed model also accounts for other features of wind fields: spatio-temporal dependencies, transport effect of wind and nonstationarity. Using one year of turbine-specific wind data, we show that the calibrated regime-switching method can offer a wide margin of improvement over existing forecasting methods in terms of both wind speed and power.

Johann Gagnon-Bartsch, Yotam Shem-Tov.

Source: The Annals of Applied Statistics, Volume 13, Number 3, 1464--1483.

Abstract:
The gold standard for identifying causal relationships is a randomized controlled experiment. In many applications in the social sciences and medicine, the researcher does not control the assignment mechanism and instead may rely upon natural experiments or matching methods as a substitute to experimental randomization. The standard testable implication of random assignment is covariate balance between the treated and control units. Covariate balance is commonly used to validate the claim of as good as random assignment. We propose a new nonparametric test of covariate balance. Our Classification Permutation Test (CPT) is based on a combination of classification methods (e.g., random forests) with Fisherian permutation inference. We revisit four real data examples and present Monte Carlo power simulations to demonstrate the applicability of the CPT relative to other nonparametric tests of equality of multivariate distributions.

Jeng-Min Chiou, Yu-Ting Chen, Tailen Hsing.

Source: The Annals of Applied Statistics, Volume 13, Number 3, 1430--1463.

Abstract:
Motivated by the study of road segmentation partitioned by shifts in traffic conditions along a freeway, we introduce a two-stage procedure, Dynamic Segmentation and Backward Elimination (DSBE), for identifying multiple changes in the mean functions for a sequence of functional data. The Dynamic Segmentation procedure searches for all possible changepoints using the derived global optimality criterion coupled with the local strategy of at-most-one-changepoint by dividing the entire sequence into individual subsequences that are recursively adjusted until convergence. Then, the Backward Elimination procedure verifies these changepoints by iteratively testing the unlikely changes to ensure their significance until no more changepoints can be removed. By combining the local strategy with the global optimal changepoint criterion, the DSBE algorithm is conceptually simple and easy to implement and performs better than the binary segmentation-based approach at detecting small multiple changes. The consistency property of the changepoint estimators and the convergence of the algorithm are proved. We apply DSBE to detect changes in traffic streams through real freeway traffic data. The practical performance of DSBE is also investigated through intensive simulation studies for various scenarios.

Lekha Patel, Nils Gustafsson, Yu Lin, Raimund Ober, Ricardo Henriques, Edward Cohen.

Source: The Annals of Applied Statistics, Volume 13, Number 3, 1397--1429.

Abstract:
Fluorescing molecules (fluorophores) that stochastically switch between photon-emitting and dark states underpin some of the most celebrated advancements in super-resolution microscopy. While this stochastic behavior has been heavily exploited, full characterization of the underlying models can potentially drive forward further imaging methodologies. Under the assumption that fluorophores move between fluorescing and dark states as continuous time Markov processes, the goal is to use a sequence of images to select a model and estimate the transition rates. We use a hidden Markov model to relate the observed discrete time signal to the hidden continuous time process. With imaging involving several repeat exposures of the fluorophore, we show the observed signal depends on both the current and past states of the hidden process, producing emission probabilities that depend on the transition rate parameters to be estimated. To tackle this unusual coupling of the transition and emission probabilities, we conceive transmission (transition-emission) matrices that capture all dependencies of the model. We provide a scheme of computing these matrices and adapt the forward-backward algorithm to compute a likelihood which is readily optimized to provide rate estimates. When confronted with several model proposals, combining this procedure with the Bayesian Information Criterion provides accurate model selection.

Lin Liu, Yuqi Qiu, Loki Natarajan, Karen Messer.

Source: The Annals of Applied Statistics, Volume 13, Number 3, 1370--1396.

Abstract:
It is common to encounter missing data among the potential predictor variables in the setting of model selection. For example, in a recent study we attempted to improve the US guidelines for risk stratification after screening colonoscopy ( Cancer Causes Control 27 (2016) 1175–1185), with the aim to help reduce both overuse and underuse of follow-on surveillance colonoscopy. The goal was to incorporate selected additional informative variables into a neoplasia risk-prediction model, going beyond the three currently established risk factors, using a large dataset pooled from seven different prospective studies in North America. Unfortunately, not all candidate variables were collected in all studies, so that one or more important potential predictors were missing on over half of the subjects. Thus, while variable selection was a main focus of the study, it was necessary to address the substantial amount of missing data. Multiple imputation can effectively address missing data, and there are also good approaches to incorporate the variable selection process into model-based confidence intervals. However, there is not consensus on appropriate methods of inference which address both issues simultaneously. Our goal here is to study the properties of model-based confidence intervals in the setting of imputation for missing data followed by variable selection. We use both simulation and theory to compare three approaches to such post-imputation-selection inference: a multiple-imputation approach based on Rubin’s Rules for variance estimation ( Comput. Statist. Data Anal. 71 (2014) 758–770); a single imputation-selection followed by bootstrap percentile confidence intervals; and a new bootstrap model-averaging approach presented here, following Efron ( J. Amer. Statist. Assoc. 109 (2014) 991–1007). We investigate relative strengths and weaknesses of each method. The “Rubin’s Rules” multiple imputation estimator can have severe undercoverage, and is not recommended. The imputation-selection estimator with bootstrap percentile confidence intervals works well. The bootstrap-model-averaged estimator, with the “Efron’s Rules” estimated variance, may be preferred if the true effect sizes are moderate. We apply these results to the colorectal neoplasia risk-prediction problem which motivated the present work.