The New England Journal of Statistics in Data Science

The tumor microenvironment (TME) is a complex and dynamic ecosystem that involves interactions between different cell types, such as cancer cells, immune cells, and stromal cells. These interactions can promote or inhibit tumor growth and affect response to therapy. Multitype Gibbs point process (MGPP) models are statistical models used to study the spatial distribution and interaction of different types of objects, such as the distribution of cell types in a tissue sample. Such models are potentially useful for investigating the spatial relationships between different cell types in the tumor microenvironment, but so far studies of the TME using cell-resolution imaging have been largely limited to spatial descriptive statistics. However, MGPP models have many advantages over descriptive statistics, such as uncertainty quantification, incorporation of multiple covariates and the ability to make predictions. In this paper, we describe and apply a previously developed MGPP method, the saturated pairwise interaction Gibbs point process model, to a publicly available multiplexed imaging dataset obtained from colorectal cancer patients. Importantly, we show how these methods can be used as joint species distribution models (JSDMs) to precisely frame and answer many relevant questions related to the ecology of the tumor microenvironment.

Categorical data are prevalent in almost all research fields and business applications. Their statistical analysis and inference often rely on probit/logistic regression models. For these common models, however, there is no universally adopted measure for performing goodness-of-fit analysis. To this end, [26] proposed a so-called surrogate ${R^{2}}$ that resembles the ordinary least square (OLS) ${R^{2}}$ for linear regression models. The surrogate ${R^{2}}$ used the notion of surrogacy, namely, generating a continuous response S and using it as a surrogate of the original categorical response Y [24, 25, 8]. In this paper, we develop an R package $\mathbf{SurrogateRsq}$ to implement the surrogate ${R^{2}}$ method [43]. The package is compatible with existing model fitting functions (e.g., glm(), polr(), clm(), and vglm()), and its features are exhibited in a wine rating analysis. Our package can be used jointly with other R packages developed for variable selection and model diagnostics so as to form a complete model development process. This process is summarized and demonstrated in a categorical-data-modeling workflow that practitioners can follow. To exemplify an extended utility of the surrogate-${R^{2}}$-based goodness-of-fit analysis, we also use this package to illustrate how to compare different empirical models trained from different samples in the wine rating analysis. The result suggests that the package allows us to evaluate comparability across multiple samples/models/studies that address the same or similar scientific or business questions.

Meta-analysis is a powerful tool for assessing drug safety by combining treatment-related toxicological findings across multiple studies, as clinical trials are typically underpowered for detecting adverse drug effects. However, incomplete reporting of adverse events (AEs) in published clinical studies is frequently encountered, especially if the observed number of AEs is below a pre-specified study-dependent threshold. Ignoring the censored AE information, often found in lower frequency, can significantly bias the estimated incidence rate of AEs. Despite its importance, this prevalent issue in meta-analysis has received little statistical or analytic attention in the literature. To address this challenge, we propose a Bayesian approach to accommodating the censored and possibly rare AEs for meta-analysis of safety data. Through simulation studies, we demonstrate that the proposed method can improve accuracy in point and interval estimation of incidence probabilities, particularly in the presence of censored data. Overall, the proposed method provides a practical solution that can facilitate better-informed decisions regarding drug safety.

Multivariate testing is a popular method to improve the effectiveness of digital marketing in industry. Online campaigns are often conducted across multiple platforms, such as desktops, tablets, smart phones, and smart watches. We propose minimum sliced aberration designs to accommodate online experiments with four platforms. This approach provides important insights into how different sets of design factors work differently across the four platforms, which can be used by industry for optimizing many forms of digital marketing. The effectiveness of the proposed approach is illustrated by an industrial email campaign with four platforms.

Analyzing health effects associated with exposure to environmental chemical mixtures is a challenging problem in epidemiology, toxicology, and exposure science. In particular, when there are a large number of chemicals under consideration it is difficult to estimate the interactive effects without incorporating reasonable prior information. Based on substantive considerations, researchers believe that true interactions between chemicals need to incorporate their corresponding main effects. In this paper, we use this prior knowledge through a shrinkage prior that a priori assumes an interaction term can only occur when the corresponding main effects exist. Our initial development is for logistic regression with linear chemical effects. We extend this formulation to include non-linear exposure effects and to account for exposure subject to detection limit. We develop an MCMC algorithm using a shrinkage prior that shrinks the interaction terms closer to zero as the main effects get closer to zero. We examine the performance of our methodology through simulation studies and illustrate an analysis of chemical interactions in a case-control study in cancer.

We consider a formal statistical design that allows simultaneous enrollment of a main cohort and a backfill cohort of patients in a dose-finding trial. The goal is to accumulate more information at various doses to facilitate dose optimization. The proposed design, called Bi3+3, combines the simple dose-escalation algorithm in the i3+3 design and a model-based inference under the framework of probability of decisions (POD), both previously published. As a result, Bi3+3 provides a simple algorithm for backfilling patients to lower doses in a dose-finding trial once these doses exhibit safety profile in patients. The POD framework allows dosing decisions to be made when some backfill patients are still being followed with incomplete toxicity outcomes, thereby potentially expediting the clinical trial. At the end of the trial, Bi3+3 uses both toxicity and efficacy outcomes to estimate an optimal biological dose (OBD). The proposed inference is based on a dose-response model that takes into account either a monotone or plateau dose-efficacy relationship, which are frequently encountered in modern oncology drug development. Simulation studies show promising operating characteristics of the Bi3+3 design in comparison to existing designs.

Two-sample testing is a fundamental problem in statistics. While many powerful nonparametric methods exist for both the univariate and multivariate context, it is comparatively less common to see a framework for determining which data features lead to rejection of the null. In this paper, we propose a new nonparametric two-sample test named AUGUST, which incorporates a framework for interpretation while maintaining power comparable to existing methods. AUGUST tests for inequality in distribution up to a predetermined resolution using symmetry statistics from binary expansion. Designed for univariate and low to moderate-dimensional multivariate data, this construction allows us to understand distributional differences as a combination of fundamental orthogonal signals. Asymptotic theory for the test statistic facilitates p-value computation and power analysis, and an efficient algorithm enables computation on large data sets. In empirical studies, we show that our test has power comparable to that of popular existing methods, as well as greater power in some circumstances. We illustrate the interpretability of our method using NBA shooting data.

Cancer is the second leading cause of death in the world. Diagnosing cancer early on can save many lives. Pathologists have to look at tissue microarray (TMA) images manually to identify tumors, which can be time-consuming, inconsistent and subjective. Existing automatic algorithms either have not achieved the accuracy level of a pathologist or require substantial human involvements. A major challenge is that TMA images with different shapes, sizes, and locations can have the same score. Learning staining patterns in TMA images requires a huge number of images, which are severely limited due to privacy and regulation concerns in medical organizations. TMA images from different cancer types may share certain common characteristics, but combining them directly harms the accuracy due to heterogeneity in their staining patterns. Transfer learning is an emerging learning paradigm that allows borrowing strength from similar problems. However, existing approaches typically require a large sample from similar learning problems, while TMA images of different cancer types are often available in small sample size and further existing algorithms are limited to transfer learning from one similar problem. We propose a new transfer learning algorithm that could learn from multiple related problems, where each problem has a small sample and can have a substantially different distribution from the original one. The proposed algorithm has made it possible to break the critical accuracy barrier (the 75% accuracy level of pathologists), with a reported accuracy of 75.9% on breast cancer TMA images from the Stanford Tissue Microarray Database. It is supported by recent developments in transfer learning theory and empirical evidence in clustering technology. This will allow pathologists to confidently adopt automatic algorithms in recognizing tumors consistently with a higher accuracy in real time.

In this paper, we present the U.S. Mental Health Dashboard, an R Shiny web application that facilitates exploratory data analysis of U.S. mental health data collected through national surveys. Mental health affects almost every aspect of people’s lives including their social relationships, substance use, academic success, professional productivity, and physical wellness. Even so, mental illnesses are often perceived as less legitimate or serious than physical diseases, and as a result of this stigmatization, many people suffer in silence without access to proper treatment. To address the lack of accessible healthcare information related to mental illness, the U.S. Mental Health Dashboard presents dynamic visualizations, tables, and choropleth maps of the prevalence and geographic distribution of key mental health metrics based on data from the National Survey on Drug Use and Health (NSDUH) and Behavioral Risk Factor Surveillance System (BRFSS). National and state-level estimates are provided for the civilian, non-institutionalized adult population of the United States as well as within relevant demographic subpopulations. By demonstrating the pervasiveness of mental illness and stark health inequities between demographic groups, this application aims to raise mental health awareness and reduce self-blame and stigmatization, especially for individuals that may inherently be at high risk. The U.S. Mental Health Dashboard has a wide variety of potential use cases: to illustrate to individuals suffering from mental illness and those in close proximity to them that they are not alone, identify subpopulations with the biggest need for mental health care, and help epidemiologists planning studies identify the target population for specific mental illness symptoms.

Variable selection in large-dimensional data has been extensively studied in different settings over the past decades. In a recent article, Shokoohi et. al. [29, DOI:10.1214/18-AOAS1198] proposed a method for variable selection in finite mixture of accelerated failure time regression models for studies on time-to-event data to capture heterogeneity within the population and account for censoring. In this paper, we introduce the fmrs package, which implements the variable selection methodology for such models. Furthermore, as a byproduct, the fmrs package facilitates variable selection in finite mixture regression models. The package also incorporates a tuning parameter selection mechanism based on component-wise bic. Commonly used penalties, such as Least Absolute Shrinkage and Selection Operator, and Smoothly Clipped Absolute Deviation, are integrated into fmrs. Additionally, the package offers an option for non-mixture regression models. The C language is chosen to boost the optimization speed. We provide an overview of the fmrs principles and the strategies employed for optimization. Hands-on illustrations are presented to help users get acquainted with fmrs. Finally, we apply fmrs to a lung cancer dataset and observe that a two-component mixture model reveals a subgroup with a more aggressive form of the disease, displaying a lower survival time.