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Jere Koskela, Paul A. Jenkins, Adam M. Johansen, Dario Spanò.

Source: The Annals of Statistics, Volume 48, Number 1, 560--583.

Abstract:
We study weighted particle systems in which new generations are resampled from current particles with probabilities proportional to their weights. This covers a broad class of sequential Monte Carlo (SMC) methods, widely-used in applied statistics and cognate disciplines. We consider the genealogical tree embedded into such particle systems, and identify conditions, as well as an appropriate time-scaling, under which they converge to the Kingman $n$-coalescent in the infinite system size limit in the sense of finite-dimensional distributions. Thus, the tractable $n$-coalescent can be used to predict the shape and size of SMC genealogies, as we illustrate by characterising the limiting mean and variance of the tree height. SMC genealogies are known to be connected to algorithm performance, so that our results are likely to have applications in the design of new methods as well. Our conditions for convergence are strong, but we show by simulation that they do not appear to be necessary.

Søren Wengel Mogensen, Niels Richard Hansen.

Source: The Annals of Statistics, Volume 48, Number 1, 539--559.

Abstract:
Symmetric independence relations are often studied using graphical representations. Ancestral graphs or acyclic directed mixed graphs with $m$-separation provide classes of symmetric graphical independence models that are closed under marginalization. Asymmetric independence relations appear naturally for multivariate stochastic processes, for instance, in terms of local independence. However, no class of graphs representing such asymmetric independence relations, which is also closed under marginalization, has been developed. We develop the theory of directed mixed graphs with $mu $-separation and show that this provides a graphical independence model class which is closed under marginalization and which generalizes previously considered graphical representations of local independence. Several graphs may encode the same set of independence relations and this means that in many cases only an equivalence class of graphs can be identified from observational data. For statistical applications, it is therefore pivotal to characterize graphs that induce the same independence relations. Our main result is that for directed mixed graphs with $mu $-separation each equivalence class contains a maximal element which can be constructed from the independence relations alone. Moreover, we introduce the directed mixed equivalence graph as the maximal graph with dashed and solid edges. This graph encodes all information about the edges that is identifiable from the independence relations, and furthermore it can be computed efficiently from the maximal graph.

Han Hong, Jessie Li.

Source: The Annals of Statistics, Volume 48, Number 1, 397--412.

Abstract:
This paper proposes a numerical bootstrap method that is consistent in many cases where the standard bootstrap is known to fail and where the $m$-out-of-$n$ bootstrap and subsampling have been the most commonly used inference approaches. We provide asymptotic analysis under both fixed and drifting parameter sequences, and we compare the approximation error of the numerical bootstrap with that of the $m$-out-of-$n$ bootstrap and subsampling. Finally, we discuss applications of the numerical bootstrap, such as constrained and unconstrained M-estimators converging at both regular and nonstandard rates, Laplace-type estimators, and test statistics for partially identified models.

Michael Schweinberger, Jonathan Stewart.

Source: The Annals of Statistics, Volume 48, Number 1, 374--396.

Abstract:
Statistical inference for exponential-family models of random graphs with dependent edges is challenging. We stress the importance of additional structure and show that additional structure facilitates statistical inference. A simple example of a random graph with additional structure is a random graph with neighborhoods and local dependence within neighborhoods. We develop the first concentration and consistency results for maximum likelihood and $M$-estimators of a wide range of canonical and curved exponential-family models of random graphs with local dependence. All results are nonasymptotic and applicable to random graphs with finite populations of nodes, although asymptotic consistency results can be obtained as well. In addition, we show that additional structure can facilitate subgraph-to-graph estimation, and present concentration results for subgraph-to-graph estimators. As an application, we consider popular curved exponential-family models of random graphs, with local dependence induced by transitivity and parameter vectors whose dimensions depend on the number of nodes.

Stephen M. S. Lee, Puyudi Yang.

Source: The Annals of Statistics, Volume 48, Number 1, 274--299.

Abstract:
Suppose that a confidence region is desired for a subvector $ heta $ of a multidimensional parameter $xi =( heta ,psi )$, based on an M-estimator $hat{xi }_{n}=(hat{ heta }_{n},hat{psi }_{n})$ calculated from a random sample of size $n$. Under nonstandard conditions $hat{xi }_{n}$ often converges at a nonregular rate $r_{n}$, in which case consistent estimation of the distribution of $r_{n}(hat{ heta }_{n}- heta )$, a pivot commonly chosen for confidence region construction, is most conveniently effected by the $m$ out of $n$ bootstrap. The above choice of pivot has three drawbacks: (i) the shape of the region is either subjectively prescribed or controlled by a computationally intensive depth function; (ii) the region is not transformation equivariant; (iii) $hat{xi }_{n}$ may not be uniquely defined. To resolve the above difficulties, we propose a one-dimensional pivot derived from the criterion function, and prove that its distribution can be consistently estimated by the $m$ out of $n$ bootstrap, or by a modified version of the perturbation bootstrap. This leads to a new method for constructing confidence regions which are transformation equivariant and have shapes driven solely by the criterion function. A subsampling procedure is proposed for selecting $m$ in practice. Empirical performance of the new method is illustrated with examples drawn from different nonstandard M-estimation settings. Extension of our theory to row-wise independent triangular arrays is also explored.

Adityanand Guntuboyina, Donovan Lieu, Sabyasachi Chatterjee, Bodhisattva Sen.

Source: The Annals of Statistics, Volume 48, Number 1, 205--229.

Abstract:
We study trend filtering, a relatively recent method for univariate nonparametric regression. For a given integer $rgeq1$, the $r$th order trend filtering estimator is defined as the minimizer of the sum of squared errors when we constrain (or penalize) the sum of the absolute $r$th order discrete derivatives of the fitted function at the design points. For $r=1$, the estimator reduces to total variation regularization which has received much attention in the statistics and image processing literature. In this paper, we study the performance of the trend filtering estimator for every $rgeq1$, both in the constrained and penalized forms. Our main results show that in the strong sparsity setting when the underlying function is a (discrete) spline with few “knots,” the risk (under the global squared error loss) of the trend filtering estimator (with an appropriate choice of the tuning parameter) achieves the parametric $n^{-1}$-rate, up to a logarithmic (multiplicative) factor. Our results therefore provide support for the use of trend filtering, for every $rgeq1$, in the strong sparsity setting.

Kai Tan, Lei Shi, Zhou Yu.

Source: The Annals of Statistics, Volume 48, Number 1, 64--85.

Abstract:
Sliced inverse regression (SIR) is an innovative and effective method for sufficient dimension reduction and data visualization. Recently, an impressive range of penalized SIR methods has been proposed to estimate the central subspace in a sparse fashion. Nonetheless, few of them considered the sparse sufficient dimension reduction from a decision-theoretic point of view. To address this issue, we in this paper establish the minimax rates of convergence for estimating the sparse SIR directions under various commonly used loss functions in the literature of sufficient dimension reduction. We also discover the possible trade-off between statistical guarantee and computational performance for sparse SIR. We finally propose an adaptive estimation scheme for sparse SIR which is computationally tractable and rate optimal. Numerical studies are carried out to confirm the theoretical properties of our proposed methods.

Holger Dette, Weichi Wu.

Source: The Annals of Statistics, Volume 47, Number 6, 3578--3608.

Abstract:
This paper considers the problem of testing if a sequence of means $(mu_{t})_{t=1,ldots ,n}$ of a nonstationary time series $(X_{t})_{t=1,ldots ,n}$ is stable in the sense that the difference of the means $mu_{1}$ and $mu_{t}$ between the initial time $t=1$ and any other time is smaller than a given threshold, that is $|mu_{1}-mu_{t}|leq c$ for all $t=1,ldots ,n$. A test for hypotheses of this type is developed using a bias corrected monotone rearranged local linear estimator and asymptotic normality of the corresponding test statistic is established. As the asymptotic variance depends on the location of the roots of the equation $|mu_{1}-mu_{t}|=c$ a new bootstrap procedure is proposed to obtain critical values and its consistency is established. As a consequence we are able to quantitatively describe relevant deviations of a nonstationary sequence from its initial value. The results are illustrated by means of a simulation study and by analyzing data examples.

Monika Bhattacharjee, Arup Bose.

Source: The Annals of Statistics, Volume 47, Number 6, 3470--3503.

Abstract:
Consider a high-dimensional linear time series model where the dimension $p$ and the sample size $n$ grow in such a way that $p/n o 0$. Let $hat{Gamma }_{u}$ be the $u$th order sample autocovariance matrix. We first show that the LSD of any symmetric polynomial in ${hat{Gamma }_{u},hat{Gamma }_{u}^{*},ugeq 0}$ exists under independence and moment assumptions on the driving sequence together with weak assumptions on the coefficient matrices. This LSD result, with some additional effort, implies the asymptotic normality of the trace of any polynomial in ${hat{Gamma }_{u},hat{Gamma }_{u}^{*},ugeq 0}$. We also study similar results for several independent MA processes. We show applications of the above results to statistical inference problems such as in estimation of the unknown order of a high-dimensional MA process and in graphical and significance tests for hypotheses on coefficient matrices of one or several such independent processes.

Alessandro Rinaldo, Larry Wasserman, Max G’Sell.

Source: The Annals of Statistics, Volume 47, Number 6, 3438--3469.

Abstract:
Several new methods have been recently proposed for performing valid inference after model selection. An older method is sample splitting: use part of the data for model selection and the rest for inference. In this paper, we revisit sample splitting combined with the bootstrap (or the Normal approximation). We show that this leads to a simple, assumption-lean approach to inference and we establish results on the accuracy of the method. In fact, we find new bounds on the accuracy of the bootstrap and the Normal approximation for general nonlinear parameters with increasing dimension which we then use to assess the accuracy of regression inference. We define new parameters that measure variable importance and that can be inferred with greater accuracy than the usual regression coefficients. Finally, we elucidate an inference-prediction trade-off: splitting increases the accuracy and robustness of inference but can decrease the accuracy of the predictions.

Benjamin Eltzner, Stephan F. Huckemann.

Source: The Annals of Statistics, Volume 47, Number 6, 3360--3381.

Abstract:
The (CLT) central limit theorems for generalized Fréchet means (data descriptors assuming values in manifolds, such as intrinsic means, geodesics, etc.) on manifolds from the literature are only valid if a certain empirical process of Hessians of the Fréchet function converges suitably, as in the proof of the prototypical BP-CLT [ Ann. Statist. 33 (2005) 1225–1259]. This is not valid in many realistic scenarios and we provide for a new very general CLT. In particular, this includes scenarios where, in a suitable chart, the sample mean fluctuates asymptotically at a scale $n^{alpha }$ with exponents $alpha <1/2$ with a nonnormal distribution. As the BP-CLT yields only fluctuations that are, rescaled with $n^{1/2}$, asymptotically normal, just as the classical CLT for random vectors, these lower rates, somewhat loosely called smeariness, had to date been observed only on the circle. We make the concept of smeariness on manifolds precise, give an example for two-smeariness on spheres of arbitrary dimension, and show that smeariness, although “almost never” occurring, may have serious statistical implications on a continuum of sample scenarios nearby. In fact, this effect increases with dimension, striking in particular in high dimension low sample size scenarios.

Victor Veitch, Daniel M. Roy.

Source: The Annals of Statistics, Volume 47, Number 6, 3274--3299.

Abstract:
Sparse exchangeable graphs on $mathbb{R}_{+}$, and the associated graphex framework for sparse graphs, generalize exchangeable graphs on $mathbb{N}$, and the associated graphon framework for dense graphs. We develop the graphex framework as a tool for statistical network analysis by identifying the sampling scheme that is naturally associated with the models of the framework, formalizing two natural notions of consistent estimation of the parameter (the graphex) underlying these models, and identifying general consistent estimators in each case. The sampling scheme is a modification of independent vertex sampling that throws away vertices that are isolated in the sampled subgraph. The estimators are variants of the empirical graphon estimator, which is known to be a consistent estimator for the distribution of dense exchangeable graphs; both can be understood as graph analogues to the empirical distribution in the i.i.d. sequence setting. Our results may be viewed as a generalization of consistent estimation via the empirical graphon from the dense graph regime to also include sparse graphs.

Xin Bing, Marten H. Wegkamp.

Source: The Annals of Statistics, Volume 47, Number 6, 3157--3184.

Abstract:
We consider the multivariate response regression problem with a regression coefficient matrix of low, unknown rank. In this setting, we analyze a new criterion for selecting the optimal reduced rank. This criterion differs notably from the one proposed in Bunea, She and Wegkamp ( Ann. Statist. 39 (2011) 1282–1309) in that it does not require estimation of the unknown variance of the noise, nor does it depend on a delicate choice of a tuning parameter. We develop an iterative, fully data-driven procedure, that adapts to the optimal signal-to-noise ratio. This procedure finds the true rank in a few steps with overwhelming probability. At each step, our estimate increases, while at the same time it does not exceed the true rank. Our finite sample results hold for any sample size and any dimension, even when the number of responses and of covariates grow much faster than the number of observations. We perform an extensive simulation study that confirms our theoretical findings. The new method performs better and is more stable than the procedure of Bunea, She and Wegkamp ( Ann. Statist. 39 (2011) 1282–1309) in both low- and high-dimensional settings.

Aryeh Kontorovich, Iosif Pinelis.

Source: The Annals of Statistics, Volume 47, Number 5, 2822--2854.

Abstract:
We provide an exact nonasymptotic lower bound on the minimax expected excess risk (EER) in the agnostic probably-approximately-correct (PAC) machine learning classification model and identify minimax learning algorithms as certain maximally symmetric and minimally randomized “voting” procedures. Based on this result, an exact asymptotic lower bound on the minimax EER is provided. This bound is of the simple form $c_{infty}/sqrt{ u}$ as $ u oinfty$, where $c_{infty}=0.16997dots$ is a universal constant, $ u=m/d$, $m$ is the size of the training sample and $d$ is the Vapnik–Chervonenkis dimension of the hypothesis class. It is shown that the differences between these asymptotic and nonasymptotic bounds, as well as the differences between these two bounds and the maximum EER of any learning algorithms that minimize the empirical risk, are asymptotically negligible, and all these differences are due to ties in the mentioned “voting” procedures. A few easy to compute nonasymptotic lower bounds on the minimax EER are also obtained, which are shown to be close to the exact asymptotic lower bound $c_{infty}/sqrt{ u}$ even for rather small values of the ratio $ u=m/d$. As an application of these results, we substantially improve existing lower bounds on the tail probability of the excess risk. Among the tools used are Bayes estimation and apparently new identities and inequalities for binomial distributions.

Robert A. Vandermeulen, Clayton D. Scott.

Source: The Annals of Statistics, Volume 47, Number 5, 2704--2733.

Abstract:
When estimating finite mixture models, it is common to make assumptions on the mixture components, such as parametric assumptions. In this work, we make no distributional assumptions on the mixture components and instead assume that observations from the mixture model are grouped, such that observations in the same group are known to be drawn from the same mixture component. We precisely characterize the number of observations $n$ per group needed for the mixture model to be identifiable, as a function of the number $m$ of mixture components. In addition to our assumption-free analysis, we also study the settings where the mixture components are either linearly independent or jointly irreducible. Furthermore, our analysis considers two kinds of identifiability, where the mixture model is the simplest one explaining the data, and where it is the only one. As an application of these results, we precisely characterize identifiability of multinomial mixture models. Our analysis relies on an operator-theoretic framework that associates mixture models in the grouped-sample setting with certain infinite-dimensional tensors. Based on this framework, we introduce a general spectral algorithm for recovering the mixture components.

Joshua Cape, Minh Tang, Carey E. Priebe.

Source: The Annals of Statistics, Volume 47, Number 5, 2405--2439.

Abstract:
The singular value matrix decomposition plays a ubiquitous role throughout statistics and related fields. Myriad applications including clustering, classification, and dimensionality reduction involve studying and exploiting the geometric structure of singular values and singular vectors. This paper provides a novel collection of technical and theoretical tools for studying the geometry of singular subspaces using the two-to-infinity norm. Motivated by preliminary deterministic Procrustes analysis, we consider a general matrix perturbation setting in which we derive a new Procrustean matrix decomposition. Together with flexible machinery developed for the two-to-infinity norm, this allows us to conduct a refined analysis of the induced perturbation geometry with respect to the underlying singular vectors even in the presence of singular value multiplicity. Our analysis yields singular vector entrywise perturbation bounds for a range of popular matrix noise models, each of which has a meaningful associated statistical inference task. In addition, we demonstrate how the two-to-infinity norm is the preferred norm in certain statistical settings. Specific applications discussed in this paper include covariance estimation, singular subspace recovery, and multiple graph inference. Both our Procrustean matrix decomposition and the technical machinery developed for the two-to-infinity norm may be of independent interest.

Marianna Pensky.

Source: The Annals of Statistics, Volume 47, Number 4, 2378--2403.

Abstract:
In the present paper, we consider a dynamic stochastic network model. The objective is estimation of the tensor of connection probabilities $mathbf{{Lambda}}$ when it is generated by a Dynamic Stochastic Block Model (DSBM) or a dynamic graphon. In particular, in the context of the DSBM, we derive a penalized least squares estimator $widehat{oldsymbol{Lambda}}$ of $mathbf{{Lambda}}$ and show that $widehat{oldsymbol{Lambda}}$ satisfies an oracle inequality and also attains minimax lower bounds for the risk. We extend those results to estimation of $mathbf{{Lambda}}$ when it is generated by a dynamic graphon function. The estimators constructed in the paper are adaptive to the unknown number of blocks in the context of the DSBM or to the smoothness of the graphon function. The technique relies on the vectorization of the model and leads to much simpler mathematical arguments than the ones used previously in the stationary set up. In addition, all results in the paper are nonasymptotic and allow a variety of extensions.

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.

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.

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.

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.

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.

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.

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.

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

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

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

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

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

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

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.

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

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

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