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Green criminology and green theories of justice : an introduction to a political economic view of eco-justice

Lynch, Michael J., author
9783030285739 (electronic bk.)




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Functional and preservative properties of phytochemicals

9780128196861 (electronic bk.)




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Fractures in the elderly : a guide to practical management

9783319722283 (electronic bk.)




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Extra-coronal restorations : concepts and clinical application

9783319790930 (electronic bk.)




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Early onset scoliosis : a clinical casebook

9783319715803 (electronic bk.)




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Development of biopharmaceutical drug-device products

9783030314156 (electronic bk.)




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Deep learning in medical image analysis : challenges and applications

9783030331283 (electronic bk.)




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Current microbiological research in Africa : selected applications for sustainable environmental management

9783030352967 (electronic bk.)




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Critical care : architecture and urbanism for a broken planet

9780262352871 (electronic bk.)




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Clinical manual of fever in children

El-Radhi, A. Sahib, author.
9783319923369 (electronic book)




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Clinical approaches in endodontic regeneration : current and emerging therapeutic perspectives

9783319968483 (electronic bk.)




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Clinical Manual of Dermatology

Huang, William W. author.
9783030239404




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Clinical Cases in Disorders of Melanocytes

9783030227579




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Cellular internet of things : from massive deployments to critical 5G applications

Liberg, Olof, 1943- author.
9780081029039 (electronic bk.)




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Biomedical product development : bench to bedside

9783030356262 (electronic bk.)




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Biology and physiology of freshwater neotropical fishes

9780128158739 (electronic bk.)




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Biological invasions in South Africa

9783030323943 (electronic bk.)




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Atlas of sexually transmitted diseases : clinical aspects and differential diagnosis

9783319574707 (electronic bk.)




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Apical periodontitis in root-filled teeth : endodontic retreatment and alternative approaches

9783319572505 (electronic bk.)




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Anomalies of the Developing Dentition : a Clinical Guide to Diagnosis and Management

Soxman, Jane A., author.
9783030031640 (electronic bk.)




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Anatomical chart company atlas of pathophysiology

Atlas of pathophysiology.
9781496370921




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A treatise on topical corticosteroids in dermatology : use, misuse and abuse

9789811046094




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100 cases in clinical pharmacology, therapeutics and prescribing

Layne, Kerry, author.
9780429624537 electronic book





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Penalized generalized empirical likelihood with a diverging number of general estimating equations for censored data

Niansheng Tang, Xiaodong Yan, Xingqiu Zhao.

Source: The Annals of Statistics, Volume 48, Number 1, 607--627.

Abstract:
This article considers simultaneous variable selection and parameter estimation as well as hypothesis testing in censored survival models where a parametric likelihood is not available. For the problem, we utilize certain growing dimensional general estimating equations and propose a penalized generalized empirical likelihood, where the general estimating equations are constructed based on the semiparametric efficiency bound of estimation with given moment conditions. The proposed penalized generalized empirical likelihood estimators enjoy the oracle properties, and the estimator of any fixed dimensional vector of nonzero parameters achieves the semiparametric efficiency bound asymptotically. Furthermore, we show that the penalized generalized empirical likelihood ratio test statistic has an asymptotic central chi-square distribution. The conditions of local and restricted global optimality of weighted penalized generalized empirical likelihood estimators are also discussed. We present a two-layer iterative algorithm for efficient implementation, and investigate its convergence property. The performance of the proposed methods is demonstrated by extensive simulation studies, and a real data example is provided for illustration.




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The numerical bootstrap

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.




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Concentration and consistency results for canonical and curved exponential-family models of random graphs

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.




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Statistical inference for model parameters in stochastic gradient descent

Xi Chen, Jason D. Lee, Xin T. Tong, Yichen Zhang.

Source: The Annals of Statistics, Volume 48, Number 1, 251--273.

Abstract:
The stochastic gradient descent (SGD) algorithm has been widely used in statistical estimation for large-scale data due to its computational and memory efficiency. While most existing works focus on the convergence of the objective function or the error of the obtained solution, we investigate the problem of statistical inference of true model parameters based on SGD when the population loss function is strongly convex and satisfies certain smoothness conditions. Our main contributions are twofold. First, in the fixed dimension setup, we propose two consistent estimators of the asymptotic covariance of the average iterate from SGD: (1) a plug-in estimator, and (2) a batch-means estimator, which is computationally more efficient and only uses the iterates from SGD. Both proposed estimators allow us to construct asymptotically exact confidence intervals and hypothesis tests. Second, for high-dimensional linear regression, using a variant of the SGD algorithm, we construct a debiased estimator of each regression coefficient that is asymptotically normal. This gives a one-pass algorithm for computing both the sparse regression coefficients and confidence intervals, which is computationally attractive and applicable to online data.




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Two-step semiparametric empirical likelihood inference

Francesco Bravo, Juan Carlos Escanciano, Ingrid Van Keilegom.

Source: The Annals of Statistics, Volume 48, Number 1, 1--26.

Abstract:
In both parametric and certain nonparametric statistical models, the empirical likelihood ratio satisfies a nonparametric version of Wilks’ theorem. For many semiparametric models, however, the commonly used two-step (plug-in) empirical likelihood ratio is not asymptotically distribution-free, that is, its asymptotic distribution contains unknown quantities, and hence Wilks’ theorem breaks down. This article suggests a general approach to restore Wilks’ phenomenon in two-step semiparametric empirical likelihood inferences. The main insight consists in using as the moment function in the estimating equation the influence function of the plug-in sample moment. The proposed method is general; it leads to a chi-squared limiting distribution with known degrees of freedom; it is efficient; it does not require undersmoothing; and it is less sensitive to the first-step than alternative methods, which is particularly appealing for high-dimensional settings. Several examples and simulation studies illustrate the general applicability of the procedure and its excellent finite sample performance relative to competing methods.




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Statistical inference for autoregressive models under heteroscedasticity of unknown form

Ke Zhu.

Source: The Annals of Statistics, Volume 47, Number 6, 3185--3215.

Abstract:
This paper provides an entire inference procedure for the autoregressive model under (conditional) heteroscedasticity of unknown form with a finite variance. We first establish the asymptotic normality of the weighted least absolute deviations estimator (LADE) for the model. Second, we develop the random weighting (RW) method to estimate its asymptotic covariance matrix, leading to the implementation of the Wald test. Third, we construct a portmanteau test for model checking, and use the RW method to obtain its critical values. As a special weighted LADE, the feasible adaptive LADE (ALADE) is proposed and proved to have the same efficiency as its infeasible counterpart. The importance of our entire methodology based on the feasible ALADE is illustrated by simulation results and the real data analysis on three U.S. economic data sets.




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Semiparametrically point-optimal hybrid rank tests for unit roots

Bo Zhou, Ramon van den Akker, Bas J. M. Werker.

Source: The Annals of Statistics, Volume 47, Number 5, 2601--2638.

Abstract:
We propose a new class of unit root tests that exploits invariance properties in the Locally Asymptotically Brownian Functional limit experiment associated to the unit root model. The invariance structures naturally suggest tests that are based on the ranks of the increments of the observations, their average and an assumed reference density for the innovations. The tests are semiparametric in the sense that they are valid, that is, have the correct (asymptotic) size, irrespective of the true innovation density. For a correctly specified reference density, our test is point-optimal and nearly efficient. For arbitrary reference densities, we establish a Chernoff–Savage-type result, that is, our test performs as well as commonly used tests under Gaussian innovations but has improved power under other, for example, fat-tailed or skewed, innovation distributions. To avoid nonparametric estimation, we propose a simplified version of our test that exhibits the same asymptotic properties, except for the Chernoff–Savage result that we are only able to demonstrate by means of simulations.




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Bayes and empirical-Bayes multiplicity adjustment in the variable-selection problem

James G. Scott, James O. Berger

Source: Ann. Statist., Volume 38, Number 5, 2587--2619.

Abstract:
This paper studies the multiplicity-correction effect of standard Bayesian variable-selection priors in linear regression. Our first goal is to clarify when, and how, multiplicity correction happens automatically in Bayesian analysis, and to distinguish this correction from the Bayesian Ockham’s-razor effect. Our second goal is to contrast empirical-Bayes and fully Bayesian approaches to variable selection through examples, theoretical results and simulations. Considerable differences between the two approaches are found. In particular, we prove a theorem that characterizes a surprising aymptotic discrepancy between fully Bayes and empirical Bayes. This discrepancy arises from a different source than the failure to account for hyperparameter uncertainty in the empirical-Bayes estimate. Indeed, even at the extreme, when the empirical-Bayes estimate converges asymptotically to the true variable-inclusion probability, the potential for a serious difference remains.




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A hierarchical dependent Dirichlet process prior for modelling bird migration patterns in the UK

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

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

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




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A hierarchical Bayesian model for predicting ecological interactions using scaled evolutionary relationships

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

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

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




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A statistical analysis of noisy crowdsourced weather data

Arnab Chakraborty, Soumendra Nath Lahiri, Alyson Wilson.

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

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




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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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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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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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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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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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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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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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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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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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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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Convergence of persistence diagrams for topological crackle

Takashi Owada, Omer Bobrowski.

Source: Bernoulli, Volume 26, Number 3, 2275--2310.

Abstract:
In this paper, we study the persistent homology associated with topological crackle generated by distributions with an unbounded support. Persistent homology is a topological and algebraic structure that tracks the creation and destruction of topological cycles (generalizations of loops or holes) in different dimensions. Topological crackle is a term that refers to topological cycles generated by random points far away from the bulk of other points, when the support is unbounded. We establish weak convergence results for persistence diagrams – a point process representation for persistent homology, where each topological cycle is represented by its $({mathit{birth},mathit{death}})$ coordinates. In this work, we treat persistence diagrams as random closed sets, so that the resulting weak convergence is defined in terms of the Fell topology. Using this framework, we show that the limiting persistence diagrams can be divided into two parts. The first part is a deterministic limit containing a densely-growing number of persistence pairs with a shorter lifespan. The second part is a two-dimensional Poisson process, representing persistence pairs with a longer lifespan.




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Directional differentiability for supremum-type functionals: Statistical applications

Javier Cárcamo, Antonio Cuevas, Luis-Alberto Rodríguez.

Source: Bernoulli, Volume 26, Number 3, 2143--2175.

Abstract:
We show that various functionals related to the supremum of a real function defined on an arbitrary set or a measure space are Hadamard directionally differentiable. We specifically consider the supremum norm, the supremum, the infimum, and the amplitude of a function. The (usually non-linear) derivatives of these maps adopt simple expressions under suitable assumptions on the underlying space. As an application, we improve and extend to the multidimensional case the results in Raghavachari ( Ann. Statist. 1 (1973) 67–73) regarding the limiting distributions of Kolmogorov–Smirnov type statistics under the alternative hypothesis. Similar results are obtained for analogous statistics associated with copulas. We additionally solve an open problem about the Berk–Jones statistic proposed by Jager and Wellner (In A Festschrift for Herman Rubin (2004) 319–331 IMS). Finally, the asymptotic distribution of maximum mean discrepancies over Donsker classes of functions is derived.




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Functional weak limit theorem for a local empirical process of non-stationary time series and its application

Ulrike Mayer, Henryk Zähle, Zhou Zhou.

Source: Bernoulli, Volume 26, Number 3, 1891--1911.

Abstract:
We derive a functional weak limit theorem for a local empirical process of a wide class of piece-wise locally stationary (PLS) time series. The latter result is applied to derive the asymptotics of weighted empirical quantiles and weighted V-statistics of non-stationary time series. The class of admissible underlying time series is illustrated by means of PLS linear processes and PLS ARCH processes.




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Interacting reinforced stochastic processes: Statistical inference based on the weighted empirical means

Giacomo Aletti, Irene Crimaldi, Andrea Ghiglietti.

Source: Bernoulli, Volume 26, Number 2, 1098--1138.

Abstract:
This work deals with a system of interacting reinforced stochastic processes , where each process $X^{j}=(X_{n,j})_{n}$ is located at a vertex $j$ of a finite weighted directed graph, and it can be interpreted as the sequence of “actions” adopted by an agent $j$ of the network. The interaction among the dynamics of these processes depends on the weighted adjacency matrix $W$ associated to the underlying graph: indeed, the probability that an agent $j$ chooses a certain action depends on its personal “inclination” $Z_{n,j}$ and on the inclinations $Z_{n,h}$, with $h eq j$, of the other agents according to the entries of $W$. The best known example of reinforced stochastic process is the Pólya urn. The present paper focuses on the weighted empirical means $N_{n,j}=sum_{k=1}^{n}q_{n,k}X_{k,j}$, since, for example, the current experience is more important than the past one in reinforced learning. Their almost sure synchronization and some central limit theorems in the sense of stable convergence are proven. The new approach with weighted means highlights the key points in proving some recent results for the personal inclinations $Z^{j}=(Z_{n,j})_{n}$ and for the empirical means $overline{X}^{j}=(sum_{k=1}^{n}X_{k,j}/n)_{n}$ given in recent papers (e.g. Aletti, Crimaldi and Ghiglietti (2019), Ann. Appl. Probab. 27 (2017) 3787–3844, Crimaldi et al. Stochastic Process. Appl. 129 (2019) 70–101). In fact, with a more sophisticated decomposition of the considered processes, we can understand how the different convergence rates of the involved stochastic processes combine. From an application point of view, we provide confidence intervals for the common limit inclination of the agents and a test statistics to make inference on the matrix $W$, based on the weighted empirical means. In particular, we answer a research question posed in Aletti, Crimaldi and Ghiglietti (2019).