Bayesian Spatial Binary Regression for Label Fusion in Structural Neuroimaging

Many analyses of neuroimaging data involve studying one or more regions of interest (ROIs) in a brain image. In order to do so, each ROI must first be identified. Since every brain is unique, the location, size, and shape of each ROI varies across subjects. Thus, each ROI in a brain image must either be manually identified or (semi-) automatically delineated, a task referred to as segmentation. Automatic segmentation often involves mapping a previously manually segmented image to a new brain image and propagating the labels to obtain an estimate of where each ROI is located in the new image. A more recent approach to this problem is to propagate labels from multiple manually segmented atlases and combine the results using a process known as label fusion. To date, most label fusion algorithms either employ voting procedures or impose prior structure and subsequently find the maximum a posteriori estimator (i.e., the posterior mode) through optimization. We propose using a fully Bayesian spatial regression model for label fusion that facilitates direct incorporation of covariate information while making accessible the entire posterior distribution. We discuss the implementation of our model via Markov chain Monte Carlo and illustrate the procedure through both simulation and application to segmentation of the hippocampus, an anatomical structure known to be associated with Alzheimer's disease.Comment: 24 pages, 10 figure

Informative Group Testing for Multiplex Assays

Infectious disease testing frequently takes advantage of two tools–group testing and multiplex assays–to make testing timely and cost effective. Until the work of Tebbs et al. (2013) and Hou et al. (2017), there was no research available to understand how best to apply these tools simultaneously. This recent work focused on applications where each individual is considered to be identical in terms of the probability of disease. However, risk-factor information, such as past behavior and presence of symptoms, is very often available on each individual to allow one to estimate individual-specific probabilities. The purpose of our paper is to propose the first group testing algorithms for multiplex assays that take advantage of individual risk-factor information as expressed by these probabilities. We show that our methods significantly reduce the number of tests required while preserving accuracy. Throughout this paper, we focus on applying our methods with the Aptima Combo 2 Assay that is used worldwide for chlamydia and gonorrhea screening

Estimating the prevalence of two or more diseases using outcomes from multiplex group testing

When screening a population for infectious diseases, pooling individual specimens (e.g., blood, swabs, urine, etc.) can provide enormous cost savings when compared to testing specimens individually. In the biostatistics literature, testing pools of specimens is commonly known as group testing or pooled testing. Although estimating a population-level prevalence with group testing data has received a large amount of attention, most of this work has focused on applications involving a single disease, such as human immunodeficiency virus. Modern methods of screening now involve testing pools and individuals for multiple diseases simultaneously through the use of multiplex assays. Hou et al. (2017, Biometrics, 73, 656–665) and Hou et al. (2020, Biostatistics, 21, 417–431) recently proposed group testing protocols for multiplex assays and derived relevant case identification characteristics, including the expected number of tests and those which quantify classification accuracy. In this article, we describe Bayesian methods to estimate population-level disease probabilities from implementing these protocols or any other multiplex group testing protocol which might be carried out in practice. Our estimation methods can be used with multiplex assays for two or more diseases while incorporating the possibility of test misclassification for each disease. We use chlamydia and gonorrhea testing data collected at the State Hygienic Laboratory at the University of Iowa to illustrate our work. We also provide an online R resource practitioners can use to implement the methods in this article

A Gamma-frailty proportional hazards model for bivariate interval-censored data

Correlated survival data naturally arise from many clinical and epidemiological studies. For the analysis of such data, the Gamma-frailty proportional hazards (PH) model is a popular choice because the regression parameters have marginal interpretations and the statistical association between the failure times can be explicitly quantified via Kendall’s tau. Despite their popularity, Gamma-frailty PH models for correlated interval-censored data have not received as much attention as analogous models for right-censored data. A Gamma-frailty PH model for bivariate interval-censored data is presented and an easy to implement expectation–maximization (EM) algorithm for model fitting is developed. The proposed model adopts a monotone spline representation for the purposes of approximating the unknown conditional cumulative baseline hazard functions, significantly reducing the number of unknown parameters while retaining modeling flexibility. The EM algorithm was derived from a data augmentation procedure involving latent Poisson random variables. Extensive numerical studies illustrate that the proposed method can provide reliable estimation and valid inference, and is moreover robust to the misspecification of the frailty distribution. To further illustrate its use, the proposed method is used to analyze data from an epidemiological study of sexually transmitted infections

Group testing models with unknown link function

Group testing through the use of pooling has proven to be an efficient method of reducing the time and cost associated with screening for a binary characteristic of interest such as infection status. A topic of key interest in this area involves the development of regression models that relate the individual level covariates to the binary pool testing responses. The research in this area has primarily focused on parametric regression models. In this poster, we will introduce a new estimation method which can handle multi-dimensional covariates while assuming the link is unknown. The asymptotic properties of our estimators are also presented. We investigate the performance of our method through simulation and by applying it to a hepatitis data set obtained from the National Health and Nutrition Examination Survey

binGroup2: Statistical Tools for Infection Identification via Group Testing

Group testing is the process of testing items as an amalgamation, rather than separately, to determine the binary status for each item. Its use was especially important during the COVID-19 pandemic through testing specimens for SARS-CoV-2. The adoption of group testing for this and many other applications is because members of a negative testing group can be declared negative with potentially only one test. This subsequently leads to significant increases in laboratory testing capacity. Whenever a group testing algorithm is put into practice, it is critical for laboratories to understand the algorithm’s operating characteristics, such as the expected number of tests. Our paper presents the binGroup2 package that provides the statistical tools for this purpose. This R package is the first to address the identification aspect of group testing for a wide variety of algorithms. We illustrate its use through COVID-19 and chlamydia/gonorrhea applications of group testing

A flexible, computationally efficient method for fitting the proportional hazards model to interval-censored data: A Novel Method for Fitting the Proportional Hazards Model to Interval-Censored Data

The proportional hazards model (PH) is currently the most popular regression model for analyzing time-to-event data. Despite its popularity, the analysis of interval-censored data under the PH model can be challenging using many available techniques. This paper presents a new method for analyzing interval-censored data under the PH model. The proposed approach uses a monotone spline representation to approximate the unknown nondecreasing cumulative baseline hazard function. Formulating the PH model in this fashion results in a finite number of parameters to estimate while maintaining substantial modeling flexibility. A novel expectation-maximization (EM) algorithm is developed for finding the maximum likelihood estimates of the parameters. The derivation of the EM algorithm relies on a two-stage data augmentation involving latent Poisson random variables. The resulting algorithm is easy to implement, robust to initialization, enjoys quick convergence, and provides closed-form variance estimates. The performance of the proposed regression methodology is evaluated through a simulation study, and is further illustrated using data from a large population-based randomized trial designed and sponsored by the United States National Cancer Institute

Quantifying the relationship between human Lyme disease and Borrelia burgdorferi exposure in domestic dogs

Lyme disease (LD) is the most common vector-borne disease in the United States. Early confirmatory diagnosis remains a challenge, while the disease can be debilitating if left untreated. Further, the decision to test is complicated by under-reporting, low positive predictive values of testing in non-endemic areas and travel, which together exacerbate the difficulty in identification of newly endemic areas or areas of emerging concern. Spatio-temporal analyses at the national scale are critical to establishing a baseline human LD risk assessment tool that would allow for the detection of changes in these areas. A well-established surrogate for human LD incidence is canine LD seroprevalence, making it a strong candidate covariate for use in such analyses. In this paper, Bayesian statistical methods were used to fit a spatio-temporal spline regression model to estimate the relationship between human LD incidence and canine seroprevalence, treating the latter as an explanatory covariate. A strong non-linear monotonically increasing association was found. That is, this analysis suggests that mean incidence in humans increases with canine seroprevalence until the seroprevalence in dogs reaches approximately 30%. This finding reinforces the use of canines as sentinels for human LD risk, especially with respect to identifying geographic areas of concern for potential human exposure