The assassination of President John Fitzgerald Kennedy (JFK) traumatized the nation. In this paper we show that evidence used to rule out a second assassin is fundamentally flawed. This paper discusses new compositional analyses of bullets reportedly to have been derived from the same batch as those used in the assassination. The new analyses show that the bullet fragments involved in the assassination are not nearly as rare as previously reported. In particular, the new test results are compared to key bullet composition testimony presented before the House Select Committee on Assassinations (HSCA). Matches of bullets within the same box of bullets are shown to be much more likely than indicated in the House Select Committee on Assassinations’ testimony. Additionally, we show that one of the ten test bullets is considered a match to one or more assassination fragments. This finding means that the bullet fragments from the assassination that match could have come from three or more separate bullets. Finally, this paper presents a case for reanalyzing the assassination bullet fragments and conducting the necessary supporting scientific studies. These analyses will shed light on whether the five bullet fragments constitute three or more separate bullets. If the assassination fragments are derived from three or more separate bullets, then a second assassin is likely, as the additional bullet would not easily be attributable to the main suspect, Mr. Oswald, under widely accepted shooting scenarios [see Posner (1993), Case Closed, Bantam, New York].

We consider “one-at-a-time” coordinate-wise descent algorithms for a class of convex optimization problems. An algorithm of this kind has been proposed for the L₁-penalized regression (lasso) in the literature, but it seems to have been largely ignored. Indeed, it seems that coordinate-wise algorithms are not often used in convex optimization. We show that this algorithm is very competitive with the well-known LARS (or homotopy) procedure in large lasso problems, and that it can be applied to related methods such as the garotte and elastic net. It turns out that coordinate-wise descent does not work in the “fused lasso,” however, so we derive a generalized algorithm that yields the solution in much less time that a standard convex optimizer. Finally, we generalize the procedure to the two-dimensional fused lasso, and demonstrate its performance on some image smoothing problems.

In microarray technology, a number of critical steps are required to convert the raw measurements into the data relied upon by biologists and clinicians. These data manipulations, referred to as preprocessing, influence the quality of the ultimate measurements and studies that rely upon them. Standard operating procedure for microarray researchers is to use preprocessed data as the starting point for the statistical analyses that produce reported results. This has prevented many researchers from carefully considering their choice of preprocessing methodology. Furthermore, the fact that the preprocessing step affects the stochastic properties of the final statistical summaries is often ignored. In this paper we propose a statistical framework that permits the integration of preprocessing into the standard statistical analysis flow of microarray data. This general framework is relevant in many microarray platforms and motivates targeted analysis methods for specific applications. We demonstrate its usefulness by applying the idea in three different applications of the technology.

It is now widely accepted that forensic DNA profiles are rare, so it was a surprise to some people that different people represented in offender databases are being found to have the same profile. In the first place this is just an illustration of the birthday problem, but a deeper analysis must take into account dependencies among profiles caused by family or population membership.

Several different types of statistical interaction are defined and distinguished, primarily on the basis of the nature of the factors defining the interaction. Illustrative examples, mostly epidemiological, are given. The emphasis is primarily on interpretation rather than on methods for detecting interactions.

Recently there has been much interest in data that, in statistical language, may be described as having a large crossed and severely unbalanced random effects structure. Such data sets arise for recommender engines and information retrieval problems. Many large bipartite weighted graphs have this structure too. We would like to assess the stability of algorithms fit to such data. Even for linear statistics, a naive form of bootstrap sampling can be seriously misleading and McCullagh [Bernoulli 6 (2000) 285–301] has shown that no bootstrap method is exact. We show that an alternative bootstrap separately resampling rows and columns of the data matrix satisfies a mean consistency property even in heteroscedastic crossed unbalanced random effects models. This alternative does not require the user to fit a crossed random effects model to the data.

The arrival process of bidders and bids in online auctions is important for studying and modeling supply and demand in the online marketplace. A popular assumption in the online auction literature is that a Poisson bidder arrival process is a reasonable approximation. This approximation underlies theoretical derivations, statistical models and simulations used in field studies. However, when it comes to the bid arrivals, empirical research has shown that the process is far from Poisson, with early bidding and last-moment bids taking place. An additional feature that has been reported by various authors is an apparent self-similarity in the bid arrival process. Despite the wide evidence for the changing bidding intensities and the self-similarity, there has been no rigorous attempt at developing a model that adequately approximates bid arrivals and accounts for these features. The goal of this paper is to introduce a family of distributions that well-approximate the bid time distribution in hard-close auctions. We call this the BARISTA process (Bid ARrivals In STAges) because of its ability to generate different intensities at different stages. We describe the properties of this model, show how to simulate bid arrivals from it, and how to use it for estimation and inference. We illustrate its power and usefulness by fitting simulated and real data from eBay.com. Finally, we show how a Poisson bidder arrival process relates to a BARISTA bid arrival process.

CD8 T cells are specialized immune cells that play an important role in the regulation of antiviral immune response and the generation of protective immunity. In this paper we investigate the differentiation of memory CD8 T cells in the immune response using a short time course microarray experiment. Structurally, this experiment is similar to many in that it involves measurements taken on independent samples, in one biological group, at a small number of irregularly spaced time points, and exhibiting patterns of temporal nonstationarity. To analyze this CD8 T-cell experiment, we develop a hierarchical state space model so that we can: (1) detect temporally differentially expressed genes, (2) identify the direction of successive changes over time, and (3) assess the magnitude of successive changes over time. We incorporate hidden Markov models into our model to utilize the information embedded in the time series and set up the proposed hierarchical state space model in an empirical Bayes framework to utilize the population information from the large-scale data. Analysis of the CD8 T-cell experiment using the proposed model results in biologically meaningful findings. Temporal patterns involved in the differentiation of memory CD8 T cells are summarized separately and performance of the proposed model is illustrated in a simulation study.

Estimation of the allele frequency at genetic markers is a key ingredient in biological and biomedical research, such as studies of human genetic variation or of the genetic etiology of heritable traits. As genetic data becomes increasingly available, investigators face a dilemma: when should data from other studies and population subgroups be pooled with the primary data? Pooling additional samples will generally reduce the variance of the frequency estimates; however, used inappropriately, pooled estimates can be severely biased due to population stratification. Because of this potential bias, most investigators avoid pooling, even for samples with the same ethnic background and residing on the same continent. Here, we propose an empirical Bayes approach for estimating allele frequencies of single nucleotide polymorphisms. This procedure adaptively incorporates genotypes from related samples, so that more similar samples have a greater influence on the estimates. In every example we have considered, our estimator achieves a mean squared error (MSE) that is smaller than either pooling or not, and sometimes substantially improves over both extremes. The bias introduced is small, as is shown by a simulation study that is carefully matched to a real data example. Our method is particularly useful when small groups of individuals are genotyped at a large number of markers, a situation we are likely to encounter in a genome-wide association study.

A significant problem with most functional data analyses is that of misaligned curves. Without adjustment, even an analysis as simple as estimation of the mean will fail. One common method to synchronize a set of curves involves equating “landmarks” such as peaks or troughs. The landmarks method can work well but will fail if marker events can not be identified or are missing from some curves. An alternative approach, the “continuous monotone registration” method, works by transforming the curves so that they are as close as possible to a target function. This method can also perform well but is highly dependent on identifying an accurate target function. We develop an alignment method based on equating the “moments” of a given set of curves. These moments are intended to capture the locations of important features which may represent local behavior, such as maximums and minimums, or more global characteristics, such as the slope of the curve averaged over time. Our method works by equating the moments of the curves while also shrinking toward a common shape. This allows us to capture the advantages of both the landmark and continuous monotone registration approaches. The method is illustrated on several data sets and a simulation study is performed.

Data on functional disability are of widespread policy interest in the United States, especially with respect to planning for Medicare and Social Security for a growing population of elderly adults. We consider an extract of functional disability data from the National Long Term Care Survey (NLTCS) and attempt to develop disability profiles using variations of the Grade of Membership (GoM) model. We first describe GoM as an individual-level mixture model that allows individuals to have partial membership in several mixture components simultaneously. We then prove the equivalence between individual-level and population-level mixture models, and use this property to develop a Markov Chain Monte Carlo algorithm for Bayesian estimation of the model. We use our approach to analyze functional disability data from the NLTCS.

It is well known that correlations in microarray data represent a serious nuisance deteriorating the performance of gene selection procedures. This paper is intended to demonstrate that the correlation structure of microarray data provides a rich source of useful information. We discuss distinct correlation substructures revealed in microarray gene expression data by an appropriate ordering of genes. These substructures include stochastic proportionality of expression signals in a large percentage of all gene pairs, negative correlations hidden in ordered gene triples, and a long sequence of weakly dependent random variables associated with ordered pairs of genes. The reported striking regularities are of general biological interest and they also have far-reaching implications for theory and practice of statistical methods of microarray data analysis. We illustrate the latter point with a method for testing differential expression of nonoverlapping gene pairs. While designed for testing a different null hypothesis, this method provides an order of magnitude more accurate control of type 1 error rate compared to conventional methods of individual gene expression profiling. In addition, this method is robust to the technical noise. Quantitative inference of the correlation structure has the potential to extend the analysis of microarray data far beyond currently practiced methods.

The spatial scan statistic is widely used in epidemiology and medical studies as a tool to identify hotspots of diseases. The classical spatial scan statistic assumes the number of disease cases in different locations have independent Poisson distributions, while in practice the data may exhibit overdispersion and spatial correlation. In this work, we examine the behavior of the spatial scan statistic when overdispersion and spatial correlation are present, and propose a modified spatial scan statistic to account for that. Some theoretical results are provided to demonstrate that ignoring the overdispersion and spatial correlation leads to an increased rate of false positives, which is verified through a simulation study. Simulation studies also show that our modified procedure can substantially reduce the rate of false alarms. Two data examples involving brain cancer cases in New Mexico and chickenpox incidence data in France are used to illustrate the practical relevance of the modified procedure.

This paper gives a method for computing distributions associated with patterns in the state sequence of a hidden Markov model, conditional on observing all or part of the observation sequence. Probabilities are computed for very general classes of patterns (competing patterns and generalized later patterns), and thus, the theory includes as special cases results for a large class of problems that have wide application. The unobserved state sequence is assumed to be Markovian with a general order of dependence. An auxiliary Markov chain is associated with the state sequence and is used to simplify the computations. Two examples are given to illustrate the use of the methodology. Whereas the first application is more to illustrate the basic steps in applying the theory, the second is a more detailed application to DNA sequences, and shows that the methods can be adapted to include restrictions related to biological knowledge.

A substantial focus of research in molecular biology are gene regulatory networks: the set of transcription factors and target genes which control the involvement of different biological processes in living cells. Previous statistical approaches for identifying gene regulatory networks have used gene expression data, ChIP binding data or promoter sequence data, but each of these resources provides only partial information. We present a Bayesian hierarchical model that integrates all three data types in a principled variable selection framework. The gene expression data are modeled as a function of the unknown gene regulatory network which has an informed prior distribution based upon both ChIP binding and promoter sequence data. We also present a variable weighting methodology for the principled balancing of multiple sources of prior information. We apply our procedure to the discovery of gene regulatory relationships in Saccharomyces cerevisiae (Yeast) for which we can use several external sources of information to validate our results. Our inferred relationships show greater biological relevance on the external validation measures than previous data integration methods. Our model also estimates synergistic and antagonistic interactions between transcription factors, many of which are validated by previous studies. We also evaluate the results from our procedure for the weighting for multiple sources of prior information. Finally, we discuss our methodology in the context of previous approaches to data integration and Bayesian variable selection.