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Efficient real-time monitoring of an emerging influenza pandemic: How feasible?

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.




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Integrative survival analysis with uncertain event times in application to a suicide risk study

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.




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BART with targeted smoothing: An analysis of patient-specific stillbirth risk

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 .




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A general theory for preferential sampling in environmental networks

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.




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Hierarchical infinite factor models for improving the prediction of surgical complications for geriatric patients

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.




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Bayesian indicator variable selection to incorporate hierarchical overlapping group structure in multi-omics applications

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.




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On Bayesian new edge prediction and anomaly detection in computer networks

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.




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Scalable high-resolution forecasting of sparse spatiotemporal events with kernel methods: A winning solution to the NIJ “Real-Time Crime Forecasting Challenge”

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.




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A hierarchical curve-based approach to the analysis of manifold data

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.




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New formulation of the logistic-Gaussian process to analyze trajectory tracking data

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.




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Empirical Bayes analysis of RNA sequencing experiments with auxiliary information

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.




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Outline analyses of the called strike zone in Major League Baseball

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.




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Propensity score weighting for causal inference with multiple treatments

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.




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Predicting paleoclimate from compositional data using multivariate Gaussian process inverse prediction

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.




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A nonparametric spatial test to identify factors that shape a microbiome

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.




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A latent discrete Markov random field approach to identifying and classifying historical forest communities based on spatial multivariate tree species counts

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.




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Objective Bayes model selection of Gaussian interventional essential graphs for the identification of signaling pathways

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.




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Fitting a deeply nested hierarchical model to a large book review dataset using a moment-based estimator

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.




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Spatial modeling of trends in crime over time in Philadelphia

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.




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Principal nested shape space analysis of molecular dynamics data

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.




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Microsimulation model calibration using incremental mixture approximate Bayesian computation

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.




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Prediction of small area quantiles for the conservation effects assessment project using a mixed effects quantile regression model

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.




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Fire seasonality identification with multimodality tests

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.




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Statistical inference for partially observed branching processes with application to cell lineage tracking of in vivo hematopoiesis

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.




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Estimating the rate constant from biosensor data via an adaptive variational Bayesian approach

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.




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A semiparametric modeling approach using Bayesian Additive Regression Trees with an application to evaluate heterogeneous treatment effects

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.




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Radio-iBAG: Radiomics-based integrative Bayesian analysis of multiplatform genomic data

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.




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Bayesian methods for multiple mediators: Relating principal stratification and causal mediation in the analysis of power plant emission controls

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.




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Approximate inference for constructing astronomical catalogs from images

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.




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Oblique random survival forests

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).




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Wavelet spectral testing: Application to nonstationary circadian rhythms

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.




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Bayesian modeling of the structural connectome for studying Alzheimer’s disease

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.




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Incorporating conditional dependence in latent class models for probabilistic record linkage: Does it matter?

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.




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A hierarchical Bayesian model for single-cell clustering using RNA-sequencing data

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.




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A Bayesian mark interaction model for analysis of tumor pathology images

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.




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Sequential decision model for inference and prediction on nonuniform hypergraphs with application to knot matching from computational forestry

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.




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RCRnorm: An integrated system of random-coefficient hierarchical regression models for normalizing NanoString nCounter data

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.




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Modeling seasonality and serial dependence of electricity price curves with warping functional autoregressive dynamics

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.




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Distributional regression forests for probabilistic precipitation forecasting in complex terrain

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.




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Network modelling of topological domains using Hi-C data

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.




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Spatio-temporal short-term wind forecast: A calibrated regime-switching method

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.




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The classification permutation test: A flexible approach to testing for covariate imbalance in observational studies

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.




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Identifying multiple changes for a functional data sequence with application to freeway traffic segmentation

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.




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Imputation and post-selection inference in models with missing data: An application to colorectal cancer surveillance guidelines

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.




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Introduction to papers on the modeling and analysis of network data—II

Stephen E. Fienberg

Source: Ann. Appl. Stat., Volume 4, Number 2, 533--534.




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Stratonovich type integration with respect to fractional Brownian motion with Hurst parameter less than $1/2$

Jorge A. León.

Source: Bernoulli, Volume 26, Number 3, 2436--2462.

Abstract:
Let $B^{H}$ be a fractional Brownian motion with Hurst parameter $Hin (0,1/2)$ and $p:mathbb{R} ightarrow mathbb{R}$ a polynomial function. The main purpose of this paper is to introduce a Stratonovich type stochastic integral with respect to $B^{H}$, whose domain includes the process $p(B^{H})$. That is, an integral that allows us to integrate $p(B^{H})$ with respect to $B^{H}$, which does not happen with the symmetric integral given by Russo and Vallois ( Probab. Theory Related Fields 97 (1993) 403–421) in general. Towards this end, we combine the approaches utilized by León and Nualart ( Stochastic Process. Appl. 115 (2005) 481–492), and Russo and Vallois ( Probab. Theory Related Fields 97 (1993) 403–421), whose aims are to extend the domain of the divergence operator for Gaussian processes and to define some stochastic integrals, respectively. Then, we study the relation between this Stratonovich integral and the extension of the divergence operator (see León and Nualart ( Stochastic Process. Appl. 115 (2005) 481–492)), an Itô formula and the existence of a unique solution of some Stratonovich stochastic differential equations. These last results have been analyzed by Alòs, León and Nualart ( Taiwanese J. Math. 5 (2001) 609–632), where the Hurst paramert $H$ belongs to the interval $(1/4,1/2)$.




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Local law and Tracy–Widom limit for sparse stochastic block models

Jong Yun Hwang, Ji Oon Lee, Wooseok Yang.

Source: Bernoulli, Volume 26, Number 3, 2400--2435.

Abstract:
We consider the spectral properties of sparse stochastic block models, where $N$ vertices are partitioned into $K$ balanced communities. Under an assumption that the intra-community probability and inter-community probability are of similar order, we prove a local semicircle law up to the spectral edges, with an explicit formula on the deterministic shift of the spectral edge. We also prove that the fluctuation of the extremal eigenvalues is given by the GOE Tracy–Widom law after rescaling and centering the entries of sparse stochastic block models. Applying the result to sparse stochastic block models, we rigorously prove that there is a large gap between the outliers and the spectral edge without centering.




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Frequency domain theory for functional time series: Variance decomposition and an invariance principle

Piotr Kokoszka, Neda Mohammadi Jouzdani.

Source: Bernoulli, Volume 26, Number 3, 2383--2399.

Abstract:
This paper is concerned with frequency domain theory for functional time series, which are temporally dependent sequences of functions in a Hilbert space. We consider a variance decomposition, which is more suitable for such a data structure than the variance decomposition based on the Karhunen–Loéve expansion. The decomposition we study uses eigenvalues of spectral density operators, which are functional analogs of the spectral density of a stationary scalar time series. We propose estimators of the variance components and derive convergence rates for their mean square error as well as their asymptotic normality. The latter is derived from a frequency domain invariance principle for the estimators of the spectral density operators. This principle is established for a broad class of linear time series models. It is a main contribution of the paper.




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A refined Cramér-type moderate deviation for sums of local statistics

Xiao Fang, Li Luo, Qi-Man Shao.

Source: Bernoulli, Volume 26, Number 3, 2319--2352.

Abstract:
We prove a refined Cramér-type moderate deviation result by taking into account of the skewness in normal approximation for sums of local statistics of independent random variables. We apply the main result to $k$-runs, U-statistics and subgraph counts in the Erdős–Rényi random graph. To prove our main result, we develop exponential concentration inequalities and higher-order tail probability expansions via Stein’s method.




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Weighted Lépingle inequality

Pavel Zorin-Kranich.

Source: Bernoulli, Volume 26, Number 3, 2311--2318.

Abstract:
We prove an estimate for weighted $p$th moments of the pathwise $r$-variation of a martingale in terms of the $A_{p}$ characteristic of the weight. The novelty of the proof is that we avoid real interpolation techniques.