Searcharxiv⌕ Search

arXiv subjects

Christine B. Peterson

Publications and source records attributed to Christine B. Peterson.

At least 19 recordsLinked to original sources

Graph-Adaptive Horseshoe for Compositional Regression

Compositional predictors, such as microbiome abundances, pose unique challenges in variable selection due to their unit-sum constraint and inherent dependencies. Existing approaches often rely on fixed association graphs derived from phylogenetic or ecological distances, which may not reflect outcome-relevant relationships. We propose GRACE (GRaph-Adaptive horseshoe for Compositional rEgression), a fully Bayesian framework that enforces compositional constraints, performs variable selection, and adaptively learns an outcome-driven shrinkage graph. GRACE achieves compositionality through a novel linear reparameterization of regression coefficients, while a structured horseshoe prior induces sparsity and smooths coefficients along the learned graph. Graph learning is accomplished via scaled beta2 priors on edge weights, providing both outcome-specific adaptation and posterior uncertainty quantification. We develop an efficient Gibbs sampler incorporating elliptical slice sampling to ensure scalability in high dimensions. Through extensive simulations, GRACE demonstrates competitive predictive accuracy and improved graph recovery compared with existing methods, particularly under graph misspecification. Application to oral microbiome data from the ORIGINS study identifies taxa associated with insulin resistance and yields an outcome-driven graph summarizing how those taxa relate to the outcome, a structure that differs substantially from phylogenetic or co-occurrence networks. These findings highlight that fixed predictor graphs useful for regularization may not faithfully represent outcome-relevant feature relationships, underscoring the need for adaptive, outcome-informed approaches in compositional regression.

stat.ME↗

Flexible aggregation of compositional predictors with shared effects for microbiome association analysis

Ongoing advancements in microbiome profiling have provided unprecedented insights into the molecular dynamics of microbial communities, sparking a surge of interest in uncovering the microbiome's critical role in human health. Identifying microbial features linked to clinical outcomes, however, remains challenging due to the high-dimensional, sparse, and compositional nature of microbiome data. Additionally, many microbial taxa, although classified as distinct, may share functional roles, complicating traditional variable selection methods. To overcome these obstacles, we introduce Bayesian Regression with Agglomerated Compositional Effects (BRACE), a novel approach using a spike-and-cluster prior combining Bernoulli activity indicators, an Ewens exchangeable partition prior on the finite active set, and a projection-based constrained Gaussian prior on cluster effects to perform data-adaptive clustering and variable selection. The methodological innovation of our work lies in how we combine the Ewens partition prior with a projection-based constrained Gaussian on the cluster atoms to enforce the sum-to-zero constraint. BRACE groups microbial taxa with similar effects on the outcome, yielding more interpretable models while enabling effective dimension reduction. Through comprehensive simulations and a real-world application examining the influence of oral microbiome composition on insulin resistance, we demonstrate BRACE's superior performance over existing methods, particularly in identifying key features with shared effects on outcomes.

stat.ME↗

Bayesian Sparse Regression for Microbiome-Metabolite Data Integration

Numerous studies have shown that microbial metabolites, which represent the products of bacteria in the human gut, play a key role in shaping cancer risk and response to treatment. However, metabolite data typically contain a large proportion of missing values, which may result from either low abundance or technical challenges in data processing. Moreover, given the compositionality of microbiome data, where the observed abundances can only be interpreted on a relative scale, standard variable selection methods are not applicable. In this project, we propose a novel Bayesian regression method to address these challenges in the integration of metabolite and microbiome data. Key features of our proposed model include modeling the two different mechanisms of missingness for the metabolite data and adopting a Bayesian prior designed to address the compositional characteristics of microbiome data. We demonstrate on simulated data that our proposed model can accurately impute the unobserved true metabolite values and correctly select the relevant microbiome predictors. We further illustrate our method using real data from a study focused on understanding the interplay between the microbiome and metabolome in colorectal cancer.

stat.AP↗

Tree-Based Predictive Models for Noisy Input Data

Measurement error is prevalent across all domains of scientific research where only imprecise observations, rather than the true underlying values, can be obtained. For example, estimates of human microbiome diversity are based on small samples from a much larger, generally unobserved system and reflect both sampling error and technical variation. In high-noise settings like these, it becomes difficult to make accurate predictions and to summarize uncertainty. Methods have previously been proposed to accommodate measurement error in classic predictive models, such as linear regression. However, relatively little work has been done to address measurement error in more complex and flexible models. Bayesian additive regression trees (BART), a Bayesian nonparametric model that sums the output of many decision trees, offers robust predictions with built-in uncertainty quantification. In this work, we propose measurement error BART (meBART), a novel extension to the BART model that directly incorporates measurement error in the independent variable(s). Through simulation studies, we show that in the presence of measurement error, our model enables more accurate parameter estimation, more robust uncertainty quantification, and superior predictive performance. We illustrate the utility of our proposed approach through two biomedical applications where the predictors of interest are subject to measurement error.

stat.ME↗

Weighted Sum-of-Trees Model for Clustered Data

Clustered data, which arise when observations are nested within groups, are incredibly common in clinical, education, and social science research. Traditionally, a linear mixed model, which includes random effects to account for within-group correlation, would be used to model the observed data and make new predictions on unseen data. Some work has been done to extend the mixed model approach beyond linear regression into more complex and non-parametric models, such as decision trees and random forests. However, existing methods are limited to using the global fixed effects for prediction on data from out-of-sample groups, effectively assuming that all clusters share a common outcome model. We propose a lightweight sum-of-trees model in which we learn a decision tree for each sample group. We combine the predictions from these trees using weights so that out-of-sample group predictions are more closely aligned with the most similar groups in the training data. This strategy also allows for inference on the similarity across groups in the outcome prediction model, as the unique tree structures and variable importances for each group can be directly compared. We show our model outperforms traditional decision trees and random forests in a variety of simulation settings. Finally, we showcase our method on real-world data from the sarcoma cohort of The Cancer Genome Atlas, where patient samples are grouped by sarcoma subtype.

stat.ME↗

pared: Model selection using multi-objective optimization

Motivation: Model selection is a ubiquitous challenge in statistics. For penalized models, model selection typically entails tuning hyperparameters to maximize a measure of fit or minimize out-of-sample prediction error. However, these criteria fail to reflect other desirable characteristics, such as model sparsity, interpretability, or smoothness. Results: We present the R package pared to enable the use of multi-objective optimization for model selection. Our approach entails the use of Gaussian process-based optimization to efficiently identify solutions that represent desirable trade-offs. Our implementation includes popular models with multiple objectives including the elastic net, fused lasso, fused graphical lasso, and group graphical lasso. Our R package generates interactive graphics that allow the user to identify hyperparameter values that result in fitted models which lie on the Pareto frontier. Availability: We provide the R package pared and vignettes illustrating its application to both simulated and real data at https://github.com/priyamdas2/pared.

stat.ME↗

Shiny-MAGEC: A Bayesian R Shiny Application for Meta-analysis of Censored Adverse Events

Accurate assessment of adverse event (AE) incidence is critical in clinical cancer research for drug safety evaluation and regulatory approval. While meta-analysis serves as an essential tool to comprehensively synthesize the evidence across multiple studies, incomplete AE reporting in clinical trials remains a persistent challenge. In particular, AEs occurring below study-specific reporting thresholds are often omitted from publications, leading to left-censored data. Failure to account for these censored AE counts can result in biased AE incidence estimates. We present an R Shiny application that implements a one-stage Bayesian meta-analysis model specifically designed to incorporate censored AE data into the estimation process. This interactive tool provides a user-friendly interface for researchers to conduct AE meta-analyses and estimate the AE incidence probability following the bias-correction methods proposed by Qi et al. (2024). It also enables direct comparisons between models that either incorporate or ignore censoring, highlighting the biases introduced by conventional approaches. This tutorial demonstrates the Shiny application's functionality through an illustrative example on meta-analysis of PD-1/PD-L1 inhibitor safety and highlights the importance of this tool in improving AE risk assessment. Ultimately, the new Shiny app facilitates more accurate and transparent drug safety evaluations. The Shiny-MAGEC app is available at: https://zihanzhou98.shinyapps.io/Shiny-MAGEC/.

stat.ME↗

Bayesian network-guided sparse regression with flexible varying effects

In this paper, we propose Varying Effects Regression with Graph Estimation (VERGE), a novel Bayesian method for feature selection in regression. Our model has key aspects that allow it to leverage the complex structure of data sets arising from genomics or imaging studies. We distinguish between the predictors, which are the features utilized in the outcome prediction model, and the subject-level covariates, which modulate the effects of the predictors on the outcome. We construct a varying coefficients modeling framework where we infer a network among the predictor variables and utilize this network information to encourage the selection of related predictors. We employ variable selection spike-and-slab priors that enable the selection of both network-linked predictor variables and covariates that modify the predictor effects. We demonstrate through simulation studies that our method outperforms existing alternative methods in terms of both feature selection and predictive accuracy. We illustrate VERGE with an application to characterizing the influence of gut microbiome features on obesity, where we identify a set of microbial taxa and their ecological dependence relations. We allow subject-level covariates including sex and dietary intake variables to modify the coefficients of the microbiome predictors, providing additional insight into the interplay between these factors.

stat.ME↗

Bayesian Varying-Effects Vector Autoregressive Models for Inference of Brain Connectivity Networks and Covariate Effects in Pediatric Traumatic Brain Injury

In this paper, we develop an analytical approach for estimating brain connectivity networks that accounts for subject heterogeneity. More specifically, we consider a novel extension of a multi-subject Bayesian vector autoregressive model that estimates group-specific directed brain connectivity networks and accounts for the effects of covariates on the network edges. We adopt a flexible approach, allowing for (possibly) non-linear effects of the covariates on edge strength via a novel Bayesian nonparametric prior that employs a weighted mixture of Gaussian processes. For posterior inference, we achieve computational scalability by implementing a variational Bayes scheme. Our approach enables simultaneous estimation of group-specific networks and selection of relevant covariate effects. We show improved performance over competing two-stage approaches on simulated data. We apply our method on resting-state fMRI data from children with a history of traumatic brain injury and healthy controls to estimate the effects of age and sex on the group-level connectivities. Our results highlight differences in the distribution of parent nodes. They also suggest alteration in the relation of age, with peak edge strength in children with traumatic brain injury (TBI), and differences in effective connectivity strength between males and females.

stat.ME↗

Meta-analysis of Censored Adverse Events

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 a frequent issue, 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 common meta-analysis problem 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 improves 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.

stat.ME↗

survivalContour: Visualizing predicted survival via colored contour plots

Advances in survival analysis have facilitated unprecedented flexibility in data modeling, yet there remains a lack of tools for graphically illustrating the influence of continuous covariates on predicted survival outcomes. We propose the utilization of a colored contour plot to depict the predicted survival probabilities over time, and provide a Shiny app and R package as implementations of this tool. Our approach is capable of supporting conventional models, including the Cox and Fine-Gray models. However, its capability shines when coupled with cutting-edge machine learning models such as random survival forests and deep neural networks.

stat.AP↗

CAT: a conditional association test for microbiome data using a leave-out approach

In microbiome analysis, researchers often seek to identify taxonomic features associated with an outcome of interest. However, microbiome features are intercorrelated and linked by phylogenetic relationships, making it challenging to assess the association between an individual feature and an outcome. Researchers have developed global tests for the association of microbiome profiles with outcomes using beta diversity metrics which offer robustness to extreme values and can incorporate information on the phylogenetic tree structure. Despite the popularity of global association testing, most existing methods for follow-up testing of individual features only consider the marginal effect and do not provide relevant information for the design of microbiome interventions. This paper proposes a novel conditional association test, CAT, which can account for other features and phylogenetic relatedness when testing the association between a feature and an outcome. CAT adopts a leave-out method, measuring the importance of a feature in predicting the outcome by removing that feature from the data and quantifying how much the association with the outcome is weakened through the change in the coefficient of determination. By leveraging global tests including PERMANOVA and MiRKAT-based methods, CAT allows association testing for continuous, binary, categorical, count, survival, and correlated outcomes. Our simulation and real data application results illustrate the potential of CAT to inform the design of microbiome interventions aimed at improving clinical outcomes.

stat.ME↗

Deep Learning-Based Dose Prediction for Automated, Individualized Quality Assurance of Head and Neck Radiation Therapy Plans

Purpose: This study aimed to use deep learning-based dose prediction to assess head and neck (HN) plan quality and identify suboptimal plans. Methods: A total of 245 VMAT HN plans were created using RapidPlan knowledge-based planning (KBP). A subset of 112 high-quality plans was selected under the supervision of an HN radiation oncologist. We trained a 3D Dense Dilated U-Net architecture to predict 3-dimensional dose distributions using 3-fold cross-validation on 90 plans. Model inputs included CT images, target prescriptions, and contours for targets and organs at risk (OARs). The model's performance was assessed on the remaining 22 test plans. We then tested the application of the dose prediction model for automated review of plan quality. Dose distributions were predicted on 14 clinical plans. The predicted versus clinical OAR dose metrics were compared to flag OARs with suboptimal normal tissue sparing using a 2 Gy dose difference or 3% dose-volume threshold. OAR flags were compared to manual flags by 3 HN radiation oncologists. Results: The predicted dose distributions were of comparable quality to the KBP plans. The differences between the predicted and KBP-planned D1%, D95%, and D99% across the targets were within -2.53%(SD=1.34%), -0.42%(SD=1.27%), and -0.12%(SD=1.97%), respectively, and the OAR mean and maximum doses were within -0.33Gy(SD=1.40Gy) and -0.96Gy(SD=2.08Gy). For the plan quality assessment study, radiation oncologists flagged 47 OARs for possible plan improvement. There was high interphysician variability; 83% of physician-flagged OARs were flagged by only one of 3 physicians. The comparative dose prediction model flagged 63 OARs, including 30 of 47 physician-flagged OARs. Conclusion: Deep learning can predict high-quality dose distributions, which can be used as comparative dose distributions for automated, individualized assessment of HN plan quality.

physics.med-ph↗

Latent Network Estimation and Variable Selection for Compositional Data via Variational EM

Network estimation and variable selection have been extensively studied in the statistical literature, but only recently have those two challenges been addressed simultaneously. In this paper, we seek to develop a novel method to simultaneously estimate network interactions and associations to relevant covariates for count data, and specifically for compositional data, which have a fixed sum constraint. We use a hierarchical Bayesian model with latent layers and employ spike-and-slab priors for both edge and covariate selection. For posterior inference, we develop a novel variational inference scheme with an expectation maximization step, to enable efficient estimation. Through simulation studies, we demonstrate that the proposed model outperforms existing methods in its accuracy of network recovery. We show the practical utility of our model via an application to microbiome data. The human microbiome has been shown to contribute to many of the functions of the human body, and also to be linked with a number of diseases. In our application, we seek to better understand the interaction between microbes and relevant covariates, as well as the interaction of microbes with each other. We provide a Python implementation of our algorithm, called SINC (Simultaneous Inference for Networks and Covariates), available online.

stat.ME↗

Estimating the Optimal Linear Combination of Biomarkers using Spherically Constrained Optimization

In the context of a binary classification problem, the optimal linear combination of continuous predictors can be estimated by maximizing an empirical estimate of the area under the receiver operating characteristic (ROC) curve (AUC). For multi-category responses, the optimal predictor combination can similarly be obtained by maximization of the empirical hypervolume under the manifold (HUM). This problem is particularly relevant to medical research, where it may be of interest to diagnose a disease with various subtypes or predict a multi-category outcome. Since the empirical HUM is discontinuous, non-differentiable, and possibly multi-modal, solving this maximization problem requires a global optimization technique. Estimation of the optimal coefficient vector using existing global optimization techniques is computationally expensive, becoming prohibitive as the number of predictors and the number of outcome categories increases. We propose an efficient derivative-free black-box optimization technique based on pattern search to solve this problem. Through extensive simulation studies, we demonstrate that the proposed method achieves better performance compared to existing methods including the step-down algorithm. Finally, we illustrate the proposed method to predict swallowing difficulty after radiation therapy for oropharyngeal cancer based on radiation dose to various structures in the head and neck.

stat.ME↗

ProgPermute: Progressive permutation for a dynamic representation of the robustness of microbiome discoveries

Identification of features is a critical task in microbiome studies that is complicated by the fact that microbial data are high dimensional and heterogeneous. Masked by the complexity of the data, the problem of separating signals from noise becomes challenging and troublesome. For instance, when performing differential abundance tests, multiple testing adjustments tend to be overconservative, as the probability of a type I error (false positive) increases dramatically with the large numbers of hypotheses. Moreover, the grouping effect of interest can be obscured by heterogeneity. These factors can incorrectly lead to the conclusion that there are no differences in the microbiome compositions. We translate and represent the problem of identifying differential features as a dynamic layout of separating the signal from its random background. We propose progressive permutation as a method to achieve this process and show converging patterns. More specifically, we progressively permute the grouping factor labels of the microbiome samples and perform multiple differential abundance tests in each scenario. We then compare the signal strength of the top features from the original data with their performance in permutations, and observe an apparent decreasing trend if these top features are true positives identified from the data. We have developed this into a user-friendly RShiny tool and R package, which consist of functions that can convey the overall association between the microbiome and the grouping factor, rank the robustness of the discovered microbes, and list the discoveries, their effect sizes, and individual abundances.

stat.ME↗

Bayesian Modeling of Multiple Structural Connectivity Networks During the Progression of Alzheimer's Disease

Alzheimer's disease is the most common neurodegenerative disease. The aim of this study is to infer structural changes in brain connectivity resulting from disease progression using cortical thickness measurements from a cohort of participants who were either healthy control, or with mild cognitive impairment, or Alzheimer's disease patients. For this purpose, we develop a novel approach for inference of multiple networks with related edge values across groups. Specifically, we infer a Gaussian graphical model for each group within a joint framework, where we rely on Bayesian hierarchical priors to link the precision matrix entries across groups. Our proposal differs from existing approaches in that it flexibly learns which groups have the most similar edge values, and accounts for the strength of connection (rather than only edge presence or absence) when sharing information across groups. Our results identify key alterations in structural connectivity which may reflect disruptions to the healthy brain, such as decreased connectivity within the occipital lobe with increasing disease severity. We also illustrate the proposed method through simulations, where we demonstrate its performance in structure learning and precision matrix estimation with respect to alternative approaches.

stat.ME↗

Bayesian Inference of Networks Across Multiple Sample Groups and Data Types

In this paper, we develop a graphical modeling framework for the inference of networks across multiple sample groups and data types. In medical studies, this setting arises whenever a set of subjects, which may be heterogeneous due to differing disease stage or subtype, is profiled across multiple platforms, such as metabolomics, proteomics, or transcriptomics data. Our proposed Bayesian hierarchical model first links the network structures within each platform using a Markov random field prior to relate edge selection across sample groups, and then links the network similarity parameters across platforms. This enables joint estimation in a flexible manner, as we make no assumptions on the directionality of influence across the data types or the extent of network similarity across the sample groups and platforms. In addition, our model formulation allows the number of variables and number of subjects to differ across the data types, and only requires that we have data for the same set of groups. We illustrate the proposed approach through both simulation studies and an application to gene expression levels and metabolite abundances on subjects with varying severity levels of Chronic Obstructive Pulmonary Disease (COPD).

stat.ME↗