A novel approach to malware classification is introduced based on analysis of instruction traces that are collected dynamically from the program in question. The method has been implemented online in a sandbox environment (i.e., a security mechanism for separating running programs) at Los Alamos National Laboratory, and is intended for eventual host-based use, provided the issue of sampling the instructions executed by a given process without disruption to the user can be satisfactorily addressed. The procedure represents an instruction trace with a Markov chain structure in which the transition matrix, $\mathbf{P} $, has rows modeled as Dirichlet vectors. The malware class (malicious or benign) is modeled using a flexible spline logistic regression model with variable selection on the elements of $\mathbf{P} $, which are observed with error. The utility of the method is illustrated on a sample of traces from malware and nonmalware programs, and the results are compared to other leading detection schemes (both signature and classification based). This article also has supplementary materials available online.

ANOVA decompositions are a standard method for describing and estimating heterogeneity among the means of a response variable across levels of multiple categorical factors. In such a decomposition, the complete set of main effects and interaction terms can be viewed as a collection of vectors, matrices and arrays that share various index sets defined by the factor levels. For many types of categorical factors, it is plausible that an ANOVA decomposition exhibits some consistency across orders of effects, in that the levels of a factor that have similar main-effect coefficients may also have similar coefficients in higher-order interaction terms. In such a case, estimation of the higher-order interactions should be improved by borrowing information from the main effects and lower-order interactions. To take advantage of such patterns, this article introduces a class of hierarchical prior distributions for collections of interaction arrays that can adapt to the presence of such interactions. These prior distributions are based on a type of array-variate normal distribution, for which a covariance matrix for each factor is estimated. This prior is able to adapt to potential similarities among the levels of a factor, and incorporate any such information into the estimation of the effects in which the factor appears. In the presence of such similarities, this prior is able to borrow information from well-estimated main effects and lower-order interactions to assist in the estimation of higher-order terms for which data information is limited.

Understanding how effective high-level NICUs (neonatal intensive care units that have the capacity for sustained mechanical assisted ventilation and high volume) are compared to low-level NICUs is important and valuable for both individual mothers and for public policy decisions. The goal of this paper is to estimate the effect on mortality of premature babies being delivered in a high-level NICU vs. a low-level NICU through an observational study where there are unmeasured confounders as well as nonignorable missing covariates. We consider the use of excess travel time as an instrumental variable (IV) to control for unmeasured confounders. In order for an IV to be valid, we must condition on confounders of the IV—outcome relationship, for example, month prenatal care started must be conditioned on for excess travel time to be a valid IV. However, sometimes month prenatal care started is missing, and the missingness may be nonignorable because it is related to the not fully measured mother’s/infant’s risk of complications. We develop a method to estimate the causal effect of a treatment using an IV when there are nonignorable missing covariates as in our data, where we allow the missingness to depend on the fully observed outcome as well as the partially observed compliance class, which is a proxy for the unmeasured risk of complications. A simulation study shows that under our nonignorable missingness assumption, the commonly used estimation methods, complete-case analysis and multiple imputation by chained equations assuming missingness at random, provide biased estimates, while our method provides approximately unbiased estimates. We apply our method to the NICU study and find evidence that high-level NICUs significantly reduce deaths for babies of small gestational age, whereas for almost mature babies like 37 weeks, the level of NICUs makes little difference. A sensitivity analysis is conducted to assess the sensitivity of our conclusions to key assumptions about the missing covariates. The method we develop in this paper may be useful for many observational studies facing similar issues of unmeasured confounders and nonignorable missing data as ours.

Bounded time series consisting of rates or proportions are often encountered in applications. This manuscript proposes a practical approach to analyze bounded time series, through a beta regression model. The method allows the direct interpretation of the regression parameters on the original response scale, while properly accounting for the heteroskedasticity typical of bounded variables. The serial dependence is modeled by a Gaussian copula, with a correlation matrix corresponding to a stationary autoregressive and moving average process. It is shown that inference, prediction, and control can be carried out straightforwardly, with minor modifications to standard analysis of autoregressive and moving average models. The methodology is motivated by an application to the influenza-like-illness incidence estimated by the Google^® Flu Trends project.

Many man-made and natural phenomena, including the intensity of earthquakes, population of cities and size of international wars, are believed to follow power-law distributions. The accurate identification of power-law patterns has significant consequences for correctly understanding and modeling complex systems. However, statistical evidence for or against the power-law hypothesis is complicated by large fluctuations in the empirical distribution’s tail, and these are worsened when information is lost from binning the data. We adapt the statistically principled framework for testing the power-law hypothesis, developed by Clauset, Shalizi and Newman, to the case of binned data. This approach includes maximum-likelihood fitting, a hypothesis test based on the Kolmogorov–Smirnov goodness-of-fit statistic and likelihood ratio tests for comparing against alternative explanations. We evaluate the effectiveness of these methods on synthetic binned data with known structure, quantify the loss of statistical power due to binning, and apply the methods to twelve real-world binned data sets with heavy-tailed patterns.

Human mortality data sets can be expressed as multiway data arrays, the dimensions of which correspond to categories by which mortality rates are reported, such as age, sex, country and year. Regression models for such data typically assume an independent error distribution or an error model that allows for dependence along at most one or two dimensions of the data array. However, failing to account for other dependencies can lead to inefficient estimates of regression parameters, inaccurate standard errors and poor predictions. An alternative to assuming independent errors is to allow for dependence along each dimension of the array using a separable covariance model. However, the number of parameters in this model increases rapidly with the dimensions of the array and, for many arrays, maximum likelihood estimates of the covariance parameters do not exist. In this paper, we propose a submodel of the separable covariance model that estimates the covariance matrix for each dimension as having factor analytic structure. This model can be viewed as an extension of factor analysis to array-valued data, as it uses a factor model to estimate the covariance along each dimension of the array. We discuss properties of this model as they relate to ordinary factor analysis, describe maximum likelihood and Bayesian estimation methods, and provide a likelihood ratio testing procedure for selecting the factor model ranks. We apply this methodology to the analysis of data from the Human Mortality Database, and show in a cross-validation experiment how it outperforms simpler methods. Additionally, we use this model to impute mortality rates for countries that have no mortality data for several years. Unlike other approaches, our methodology is able to estimate similarities between the mortality rates of countries, time periods and sexes, and use this information to assist with the imputations.

A number of statistical models have been successfully developed for the analysis of high-throughput data from a single source, but few methods are available for integrating data from different sources. Here we focus on integrating gene expression levels with comparative genomic hybridization (CGH) array measurements collected on the same subjects. We specify a measurement error model that relates the gene expression levels to latent copy number states which, in turn, are related to the observed surrogate CGH measurements via a hidden Markov model. We employ selection priors that exploit the dependencies across adjacent copy number states and investigate MCMC stochastic search techniques for posterior inference. Our approach results in a unified modeling framework for simultaneously inferring copy number variants (CNV) and identifying their significant associations with mRNA transcripts abundance. We show performance on simulated data and illustrate an application to data from a genomic study on human cancer cell lines.

Genetic association analyses often involve data from multiple potentially-heterogeneous subgroups. The expected amount of heterogeneity can vary from modest (e.g., a typical meta-analysis) to large (e.g., a strong gene–environment interaction). However, existing statistical tools are limited in their ability to address such heterogeneity. Indeed, most genetic association meta-analyses use a “fixed effects” analysis, which assumes no heterogeneity. Here we develop and apply Bayesian association methods to address this problem. These methods are easy to apply (in the simplest case, requiring only a point estimate for the genetic effect and its standard error, from each subgroup) and effectively include standard frequentist meta-analysis methods, including the usual “fixed effects” analysis, as special cases. We apply these tools to two large genetic association studies: one a meta-analysis of genome-wide association studies from the Global Lipids consortium, and the second a cross-population analysis for expression quantitative trait loci (eQTLs). In the Global Lipids data we find, perhaps surprisingly, that effects are generally quite homogeneous across studies. In the eQTL study we find that eQTLs are generally shared among different continental groups, and discuss consequences of this for study design.

Conventionally, the construction of a pair-matched sample selects treated and control units and pairs them in a single step with a view to balancing observed covariates $\mathbf{x}$ and reducing the heterogeneity or dispersion of treated-minus-control response differences, $Y$. In contrast, the method of cardinality matching developed here first selects the maximum number of units subject to covariate balance constraints and, with a balanced sample for $\mathbf{x}$ in hand, then separately pairs the units to minimize heterogeneity in $Y$. Reduced heterogeneity of pair differences in responses $Y$ is known to reduce sensitivity to unmeasured biases, so one might hope that cardinality matching would succeed at both tasks, balancing $\mathbf{x}$, stabilizing $Y$. We use cardinality matching in an observational study of the effectiveness of for-profit and not-for-profit private high schools in Chile—a controversial subject in Chile—focusing on students who were in government run primary schools in 2004 but then switched to private high schools. By pairing to minimize heterogeneity in a cardinality match that has balanced covariates, a meaningful reduction in sensitivity to unmeasured biases is obtained.

The issue of using informative priors for estimation of mixtures at multiple time points is examined. Several different informative priors and an independent prior are compared using samples of actual and simulated aerosol particle size distribution (PSD) data. Measurements of aerosol PSDs refer to the concentration of aerosol particles in terms of their size, which is typically multimodal in nature and collected at frequent time intervals. The use of informative priors is found to better identify component parameters at each time point and more clearly establish patterns in the parameters over time. Some caveats to this finding are discussed.

Cryo-electron microscopy (cryo-EM) has recently emerged as a powerful tool for obtaining three-dimensional (3D) structures of biological macromolecules in native states. A minimum cryo-EM image data set for deriving a meaningful reconstruction is comprised of thousands of randomly orientated projections of identical particles photographed with a small number of electrons. The computation of 3D structure from 2D projections requires clustering, which aims to enhance the signal to noise ratio in each view by grouping similarly oriented images. Nevertheless, the prevailing clustering techniques are often compromised by three characteristics of cryo-EM data: high noise content, high dimensionality and large number of clusters. Moreover, since clustering requires registering images of similar orientation into the same pixel coordinates by 2D alignment, it is desired that the clustering algorithm can label misaligned images as outliers. Herein, we introduce a clustering algorithm $\gamma$-SUP to model the data with a $q$-Gaussian mixture and adopt the minimum $\gamma$-divergence for estimation, and then use a self-updating procedure to obtain the numerical solution. We apply $\gamma$-SUP to the cryo-EM images of two benchmark macromolecules, RNA polymerase II and ribosome. In the former case, simulated images were chosen to decouple clustering from alignment to demonstrate $\gamma$-SUP is more robust to misalignment outliers than the existing clustering methods used in the cryo-EM community. In the latter case, the clustering of real cryo-EM data by our $\gamma$-SUP method eliminates noise in many views to reveal true structure features of ribosome at the projection level.

The study of vegetation fluctuations gives valuable information toward effective land use and development. We consider this problem for the East African region based on the Normalized Difference Vegetation Index (NDVI) series from satellite remote sensing data collected between 1982 and 2006 over 8-kilometer grid points. We detect areas with significant increasing or decreasing monotonic vegetation changes using a multiple testing procedure controlling the mixed directional false discovery rate (mdFDR). Specifically, we use a three-stage directional Benjamini–Hochberg (BH) procedure with proven mdFDR control under independence and a suitable adaptive version of it. The performance of these procedures is studied through simulations before applying them to the vegetation data. Our analysis shows increasing vegetation in the Northern hemisphere as well as coastal Tanzania and generally decreasing Southern hemisphere vegetation trends, which are consistent with historical evidence.

RNA-sequencing has revolutionized biomedical research and, in particular, our ability to study gene alternative splicing. The problem has important implications for human health, as alternative splicing may be involved in malfunctions at the cellular level and multiple diseases. However, the high-dimensional nature of the data and the existence of experimental biases pose serious data analysis challenges. We find that the standard data summaries used to study alternative splicing are severely limited, as they ignore a substantial amount of valuable information. Current data analysis methods are based on such summaries and are hence suboptimal. Further, they have limited flexibility in accounting for technical biases. We propose novel data summaries and a Bayesian modeling framework that overcome these limitations and determine biases in a nonparametric, highly flexible manner. These summaries adapt naturally to the rapid improvements in sequencing technology. We provide efficient point estimates and uncertainty assessments. The approach allows to study alternative splicing patterns for individual samples and can also be the basis for downstream analyses. We found a severalfold improvement in estimation mean square error compared popular approaches in simulations, and substantially higher consistency between replicates in experimental data. Our findings indicate the need for adjusting the routine summarization and analysis of alternative splicing RNA-seq studies. We provide a software implementation in the R package casper.

Periodontal probing depth is a measure of periodontitis severity. We develop a Bayesian hierarchical model linking true pocket depth to both observed and recorded values of periodontal probing depth, while permitting correlation among measures obtained from the same mouth and between duplicate examiners’ measures obtained at the same periodontal site. Periodontal site-specific examiner effects are modeled as arising from a Dirichlet process mixture, facilitating identification of classes of sites that are measured with similar bias. Using simulated data, we demonstrate the model’s ability to recover examiner site-specific bias and variance heterogeneity and to provide cluster-adjusted point and interval agreement estimates. We conclude with an analysis of data from a probing depth calibration training exercise.

Genetic association studies have been a popular approach for assessing the association between common Single Nucleotide Polymorphisms (SNPs) and complex diseases. However, other genomic data involved in the mechanism from SNPs to disease, for example, gene expressions, are usually neglected in these association studies. In this paper, we propose to exploit gene expression information to more powerfully test the association between SNPs and diseases by jointly modeling the relations among SNPs, gene expressions and diseases. We propose a variance component test for the total effect of SNPs and a gene expression on disease risk. We cast the test within the causal mediation analysis framework with the gene expression as a potential mediator. For eQTL SNPs, the use of gene expression information can enhance power to test for the total effect of a SNP-set, which is the combined direct and indirect effects of the SNPs mediated through the gene expression, on disease risk. We show that the test statistic under the null hypothesis follows a mixture of $\chi^{2}$ distributions, which can be evaluated analytically or empirically using the resampling-based perturbation method. We construct tests for each of three disease models that are determined by SNPs only, SNPs and gene expression, or include also their interactions. As the true disease model is unknown in practice, we further propose an omnibus test to accommodate different underlying disease models. We evaluate the finite sample performance of the proposed methods using simulation studies, and show that our proposed test performs well and the omnibus test can almost reach the optimal power where the disease model is known and correctly specified. We apply our method to reanalyze the overall effect of the SNP-set and expression of the ORMDL3 gene on the risk of asthma.

In the last two decades many random graph models have been proposed to extract knowledge from networks. Most of them look for communities or, more generally, clusters of vertices with homogeneous connection profiles. While the first models focused on networks with binary edges only, extensions now allow to deal with valued networks. Recently, new models were also introduced in order to characterize connection patterns in networks through mixed memberships. This work was motivated by the need of analyzing a historical network where a partition of the vertices is given and where edges are typed. A known partition is seen as a decomposition of a network into subgraphs that we propose to model using a stochastic model with unknown latent clusters. Each subgraph has its own mixing vector and sees its vertices associated to the clusters. The vertices then connect with a probability depending on the subgraphs only, while the types of edges are assumed to be sampled from the latent clusters. A variational Bayes expectation-maximization algorithm is proposed for inference as well as a model selection criterion for the estimation of the cluster number. Experiments are carried out on simulated data to assess the approach. The proposed methodology is then applied to an ecclesiastical network in Merovingian Gaul. An R code, called Rambo, implementing the inference algorithm is available from the authors upon request.

We present a new method based on Functional Data Analysis (FDA) for detecting associations between one or more scalar covariates and a longitudinal response, while correcting for other variables. Our methods exploit the temporal structure of longitudinal data in ways that are otherwise difficult with a multivariate approach. Our procedure, from an FDA perspective, is a departure from more established methods in two key aspects. First, the raw longitudinal phenotypes are assembled into functional trajectories prior to analysis. Second, we explore an association test that is not directly based on principal components. We instead focus on quantifying the reduction in $L^{2}$ variability as a means of detecting associations. Our procedure is motivated by longitudinal genome wide association studies and, in particular, the childhood asthma management program (CAMP) which explores the long term effects of daily asthma treatments. We conduct a simulation study to better understand the advantages (and/or disadvantages) of an FDA approach compared to a traditional multivariate one. We then apply our methodology to data coming from CAMP. We find a potentially new association with a SNP negatively affecting lung function. Furthermore, this SNP seems to have an interaction effect with one of the treatments.

We propose a new parametric time-varying shared frailty model to represent changes over time in population heterogeneity, for use with bivariate current status data. The model uses a power transformation of a time-invariant frailty $U$, and is particularly convenient when $U$ is a member of the generalized gamma family. This model avoids some shortcomings of a previously suggested time-varying frailty model, notably time-dependent support. We describe some key properties of the model, including its relative frailty variance function in different settings and how the model can be fitted to data. We describe several applications to shared frailty modeling of bivariate current status data on infectious diseases, in which the frailty represents age-dependent heterogeneity in contact rates or susceptibility to infection.

Inferring time-varying networks is important to understand the development and evolution of interactions over time. However, the vast majority of currently used models assume direct measurements of node states, which are often difficult to obtain, especially in fields like cell biology, where perturbation experiments often only provide indirect information of network structure. Here we propose hidden Markov nested effects models (HM-NEMs) to model the evolving network by a Markov chain on a state space of signalling networks, which are derived from nested effects models (NEMs) of indirect perturbation data. To infer the hidden network evolution and unknown parameter, a Gibbs sampler is developed, in which sampling network structure is facilitated by a novel structural Metropolis–Hastings algorithm. We demonstrate the potential of HM-NEMs by simulations on synthetic time-series perturbation data. We also show the applicability of HM-NEMs in two real biological case studies, in one capturing dynamic crosstalk during the progression of neutrophil polarisation, and in the other inferring an evolving network underlying early differentiation of mouse embryonic stem cells.

The paramount importance of replicating associations is well recognized in the genome-wide associaton (GWA) research community, yet methods for assessing replicability of associations are scarce. Published GWA studies often combine separately the results of primary studies and of the follow-up studies. Informally, reporting the two separate meta-analyses, that of the primary studies and follow-up studies, gives a sense of the replicability of the results. We suggest a formal empirical Bayes approach for discovering whether results have been replicated across studies, in which we estimate the optimal rejection region for discovering replicated results. We demonstrate, using realistic simulations, that the average false discovery proportion of our method remains small. We apply our method to six type two diabetes (T2D) GWA studies. Out of 803 SNPs discovered to be associated with T2D using a typical meta-analysis, we discovered 219 SNPs with replicated associations with T2D. We recommend complementing a meta-analysis with a replicability analysis for GWA studies.

In this paper we propose a general framework for topic-specific summarization of large text corpora and illustrate how it can be used for the analysis of news databases. Our framework, concise comparative summarization (CCS), is built on sparse classification methods. CCS is a lightweight and flexible tool that offers a compromise between simple word frequency based methods currently in wide use and more heavyweight, model-intensive methods such as latent Dirichlet allocation (LDA). We argue that sparse methods have much to offer for text analysis and hope CCS opens the door for a new branch of research in this important field.

For a particular topic of interest (e.g., China or energy), CSS automatically labels documents as being either on- or off-topic (usually via keyword search), and then uses sparse classification methods to predict these labels with the high-dimensional counts of all the other words and phrases in the documents. The resulting small set of phrases found as predictive are then harvested as the summary.

To validate our tool, we, using news articles from the New York Times international section, designed and conducted a human survey to compare the different summarizers with human understanding. We demonstrate our approach with two case studies, a media analysis of the framing of “Egypt” in the New York Times throughout the Arab Spring and an informal comparison of the New York Times’ and Wall Street Journal’s coverage of “energy.” Overall, we find that the Lasso with $L^{2}$ normalization can be effectively and usefully used to summarize large corpora, regardless of document size.

We consider the statistical analysis of trajectories on Riemannian manifolds that are observed under arbitrary temporal evolutions. Past methods rely on cross-sectional analysis, with the given temporal registration, and consequently may lose the mean structure and artificially inflate observed variances. We introduce a quantity that provides both a cost function for temporal registration and a proper distance for comparison of trajectories. This distance is used to define statistical summaries, such as sample means and covariances, of synchronized trajectories and “Gaussian-type” models to capture their variability at discrete times. It is invariant to identical time-warpings (or temporal reparameterizations) of trajectories. This is based on a novel mathematical representation of trajectories, termed transported square-root vector field (TSRVF), and the $\mathbb{L}^{2}$ norm on the space of TSRVFs. We illustrate this framework using three representative manifolds—$\mathbb{S}^{2}$, $\mathrm{SE}(2)$ and shape space of planar contours—involving both simulated and real data. In particular, we demonstrate: (1) improvements in mean structures and significant reductions in cross-sectional variances using real data sets, (2) statistical modeling for capturing variability in aligned trajectories, and (3) evaluating random trajectories under these models. Experimental results concern bird migration, hurricane tracking and video surveillance.

Nuclear-weapon-material detection via gamma-ray sensing is routinely applied, for example, in monitoring cross-border traffic. Natural or deliberate shielding both attenuates and distorts the shape of the gamma-ray spectra of specific radionuclides, thereby making such routine applications challenging. We develop a Lagrange multiplier (LM) test for shielding. A strong advantage of the LM test is that it only requires fitting a much simpler model that assumes no shielding. We show that, under the null hypothesis and some mild regularity conditions and as the detection time increases, LM test statistic for (composite) shielding is asymptotically Chi-square with the degree of freedom equal to the presumed number of shielding materials. We also derive the local power of the LM test. Extensive simulation studies suggest that the test is robust to the number and nature of the intervening materials, which owes to the fact that common intervening materials have broadly similar attenuation functions.

Researchers have constantly asked whether stock returns can be predicted by some macroeconomic data. However, it is known that macroeconomic data may exhibit nonstationarity and/or heavy tails, which complicates existing testing procedures for predictability. In this paper we propose novel empirical likelihood methods based on some weighted score equations to test whether the monthly CRSP value-weighted index can be predicted by the log dividend-price ratio or the log earnings-price ratio. The new methods work well both theoretically and empirically regardless of the predicting variables being stationary or nonstationary or having an infinite variance.

Predictions are issued on the basis of certain information. If the forecasting mechanisms are correctly specified, a larger amount of available information should lead to better forecasts. For point forecasts, we show how the effect of increasing the information set can be quantified by using strictly consistent scoring functions, where it results in smaller average scores. Further, we show that the classical Diebold–Mariano test, based on strictly consistent scoring functions and asymptotically ideal forecasts, is a consistent test for the effect of an increase in a sequence of information sets on $h$-step point forecasts. For the value at risk (VaR), we show that the average score, which corresponds to the average quantile risk, directly relates to the expected shortfall. Thus, increasing the information set will result in VaR forecasts which lead on average to smaller expected shortfalls. We illustrate our results in simulations and applications to stock returns for unconditional versus conditional risk management as well as univariate modeling of portfolio returns versus multivariate modeling of individual risk factors. The role of the information set for evaluating probabilistic forecasts by using strictly proper scoring rules is also discussed.

This work is motivated by the analysis of the extremal behavior of buoy and satellite data describing wave conditions in the North Atlantic Ocean. The available data sets consist of time series of significant wave height (Hs) with irregular time sampling. In such a situation, the usual statistical methods for analyzing extreme values cannot be used directly. The method proposed in this paper is an extension of the peaks over threshold (POT) method, where the distribution of a process above a high threshold is approximated by a max-stable process whose parameters are estimated by maximizing a composite likelihood function. The efficiency of the proposed method is assessed on an extensive set of simulated data. It is shown, in particular, that the method is able to describe the extremal behavior of several common time series models with regular or irregular time sampling. The method is then used to analyze Hs data in the North Atlantic Ocean. The results indicate that it is possible to derive realistic estimates of the extremal properties of Hs from satellite data, despite its complex space–time sampling.