arXiv subjects

Rahul Ghosal

Publications and source records attributed to Rahul Ghosal.

At least 19 recordsLinked to original sources

arXiv2026

Penalized Cox Regression with Graph-Structured Distribution-Valued Predictors

We propose the Graph-Fused Distributional Cox Model (GFDCM), a penalized survival analysis framework for distribution-valued predictors organized on a known graph. Modern neuroimaging studies collect high-dimensional voxel-level measurements across multiple regions of interest (ROIs) with rich spatial dependency structures. Rather than reducing these to scalar summaries, GFDCM models the full distribution of voxel intensities within each ROI, retaining region-specific interpretability while exploiting spatial relationships among adjacent ROIs. The distributional associations are modeled using penalized splines. To achieve simultaneous predictor selection and graph-based fusion, we introduce a structured Graph-Fused Group LASSO (GFGL) penalty that combines a group-sparsity term for discarding irrelevant predictors with a fusion term that enforces coefficient functions for graph-adjacent predictors to be identical. A flexible alternating direction method of multipliers (ADMM) algorithm is employed to optimize the penalized partial likelihood. Numerical simulations illustrate satisfactory selection, fusion, and estimation performance of GFDCM compared with unpenalized functional Cox regression and selection-only alternatives. Finally, we apply GFDCM to baseline T1-weighted MRI data collected from 308 patients in the Alzheimer's Disease Neuroimaging Initiative (ADNI-1) to identify brain regions associated with AD conversion. The results provide clinically meaningful insights and exhibit superior predictive performance compared to traditional ROI-level summary-based approaches.

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arXiv2026

Spatially-Indexed Longitudinal Distributional Outcome Regression for Environmental Monitoring

Characterizing longitudinal changes in region-specific distribution of environmental exposures, such as total nitrate (TNO$_3$) concentrations, is critical for understanding localized ecological risks that are otherwise obscured by standard mean-level modeling. However, modeling longitudinal distributional outcomes across spatial regions presents significant methodological challenges. The random objects are spatio-temporally dependent, and mathematical constraints are inherent to distributional representations, such as, monotonicity of quantile functions. To address this, we propose a novel spatially-indexed longitudinal distributional outcome regression model. The distributional coefficients corresponding to the fixed effects of covariates are modeled using Bernstein basis polynomials, while spatio-temporal random effects are flexibly captured via tensor product expansions of splines. We develop a scalable Markov Chain Monte Carlo (MCMC) algorithm to explicitly account for spatial dependencies, and introduce a fast two-stage projected-posterior approach to preserve the monotonicity of the predicted subject-specific quantile functions. Extensive simulation studies demonstrate that the proposed framework achieves superior estimation accuracy and predictive performance compared to standard non-spatial distributional outcome regression. We apply our methodology to predict monthly, site-specific distributions of TNO$_3$ concentrations across the contiguous United States. Accounting for spatial correlation provides substantially lower uncertainty in the estimated distributional effects and improves predictive performance over the non-spatial alternative, offering a robust, interpretable tool for spatio-temporal environmental monitoring.

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arXiv2026

Variable Selection in Functional Linear Quantile Regression for Identifying Associations between Daily Patterns of Physical Activity and Cognitive Function

Quantile regression is useful for characterizing the conditional distribution of a response variable and understanding heterogeneity in the covariate effects at different quantiles. The rise of high-dimensional physiological data in biomedical research through wearable and sensor devices underscores the need for effective variable selection methods for interpretable and accurate quantile regression, which can offer robust insights into heterogeneous and dynamic covariate effects. We develop a flexible variable selection approach for functional linear quantile regression with multiple functional and scalar predictors. We use a smooth approximation of the quantile loss function and integrate functional principal component analysis (FPCA) with a group minimax concave penalty (MCP) to impose sparsity on the functional coefficients. A computationally efficient group descent algorithm is employed for optimization. Through numerical simulations, we demonstrate a satisfactory selection, estimation, and prediction accuracy of the proposed method across different quantiles for both dense and sparsely observed functional data. The proposed method is applied to accelerometer data from the 2011-2014 National Health and Nutrition Examination Survey (NHANES) to identify key time-varying distributional patterns of physical activity and demographic predictors associated with cognitive function across different quantiles. Our analysis provides new insights into the complex relationship between the daily distributional patterns of physical activity and cognitive function among older adults, capturing heterogeneous associations across different quantiles.

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arXiv2026

Multivariate Functional Principal Component Analysis for Mixed-Type mHealth Data: An Application to Mood Disorders

Modern mobile health (mHealth) assessment combines self-reported measures of participants' health experiences with passively collected health behavior data throughout the day. These data are collected across multiple measurement scales, including continuous (physical activity), truncated (pain), ordinal (mood), and binary (daily life events). When indexed by time of day and stacked across assessment domains, these data structures can be treated as multivariate functional data comprising continuous, truncated, ordinal, and binary variables. Motivated by these applications, we propose a multivariate functional principal component analysis for mixed-type data ($M^2$FPCA). The approach is based on a semiparametric Gaussian copula model and assumes that the observed data arise from an underlying multivariate generalized latent nonparanormal functional process. Latent temporal and inter-variable dependence are estimated semiparametrically through Kendall's tau bridging method. Two covariance estimation procedures are developed: a fully multivariate block-wise estimator and a computationally efficient alternative based on partial separability that assumes shared principal components across domains. The proposed method yields interpretable latent functional principal component scores that can serve as participant-specific digital biomarkers. Simulation studies demonstrate the method's competitive performance under various complex dependence structures. The method is applied to mHealth data from 307 participants in the National Institute of Mental Health Family Study of Mood and Affective Spectrum Disorders. Our approach identifies time-of-day patterns shared across mood, anxiety, energy, and physical activity that meaningfully stratify mood disorder subtypes.

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arXiv2025

Variable Selection for Fixed and Random Effects in Multilevel Functional Mixed Effects Models

We develop a new method for simultaneously selecting fixed and random effects in a multilevel functional regression model. The proposed method is motivated by accelerometer-derived physical activity data from the 2011-12 cohort of the National Health and Nutrition Examination Survey (NHANES), where we are interested in identifying age and race-specific heterogeneity in covariate effects on the diurnal patterns of physical activity across the lifespan. Existing methods for variable selection in function-on-scalar regression have primarily been designed for fixed effect selection and for single-level functional data. In high-dimensional multilevel functional regression, the presence of cluster-specific heterogeneity in covariate effects could be detected through sparsity in fixed and random effects, and for this purpose, we propose a multilevel functional mixed effects selection (MuFuMES) method. The fixed and random functional effects are modelled using splines, with spike-and-slab group lasso (SSGL) priors on the unknown parameters of interest and a computationally efficient MAP estimation approach is employed for mixed effect selection through an Expectation Conditional Maximization (ECM) algorithm. Numerical analysis using simulation study illustrates the satisfactory selection accuracy of the variable selection method in having a negligible false-positive and false-negative rate. The proposed method is applied to the accelerometer data from the NHANES 2011-12 cohort, where it effectively identifies age and race-specific heterogeneity in covariate effects on the diurnal patterns of physical activity, recovering biologically meaningful insights.

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arXiv2025

ROC Analysis with Covariate Adjustment Using Neural Network Models: Evaluating the Role of Age in the Physical Activity-Mortality Association

The receiver operating characteristic (ROC) curve and its summary measure, the Area Under the Curve (AUC), are well-established tools for evaluating the efficacy of biomarkers in biomedical studies. Compared to the traditional ROC curve, the covariate-adjusted ROC curve allows for individual evaluation of the biomarker. However, the use of machine learning models has rarely been explored in this context, despite their potential to develop more powerful and sophisticated approaches for biomarker evaluation. The goal of this paper is to propose a framework for neural network-based covariate-adjusted ROC modeling that allows flexible and nonlinear evaluation of the effectiveness of a biomarker to discriminate between two reference populations. The finite-sample performance of our method is investigated through extensive simulation tests under varying dependency structures between biomarkers, covariates, and referenced populations. The methodology is further illustrated in a clinically case study that assesses daily physical activity - measured as total activity time (TAC), a proxy for daily step count-as a biomarker to predict mortality at three, five and eight years. Analyzes stratified by sex and adjusted for age and BMI reveal distinct covariate effects on mortality outcomes. These results underscore the importance of covariate-adjusted modeling in biomarker evaluation and highlight TAC's potential as a functional capacity biomarker based on specific individual characteristics.

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arXiv2025

Model-Free Kernel Conformal Depth Measures Algorithm for Uncertainty Quantification in Regression Models in Separable Hilbert Spaces

Depth measures are powerful tools for defining level sets in emerging, non--standard, and complex random objects such as high-dimensional multivariate data, functional data, and random graphs. Despite their favorable theoretical properties, the integration of depth measures into regression modeling to provide prediction regions remains a largely underexplored area of research. To address this gap, we propose a novel, model-free uncertainty quantification algorithm based on conditional depth measures--specifically, conditional kernel mean embeddings and an integrated depth measure. These new algorithms can be used to define prediction and tolerance regions when predictors and responses are defined in separable Hilbert spaces. The use of kernel mean embeddings ensures faster convergence rates in prediction region estimation. To enhance the practical utility of the algorithms with finite samples, we also introduce a conformal prediction variant that provides marginal, non-asymptotic guarantees for the derived prediction regions. Additionally, we establish both conditional and unconditional consistency results, as well as fast convergence rates in certain homoscedastic settings. We evaluate the finite--sample performance of our model in extensive simulation studies involving various types of functional data and traditional Euclidean scenarios. Finally, we demonstrate the practical relevance of our approach through a digital health application related to physical activity, aiming to provide personalized recommendations

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arXiv2025

Variable Selection in Functional Linear Cox Model

Modern biomedical studies frequently collect complex, high-dimensional physiological signals using wearables and sensors along with time-to-event outcomes, making efficient variable selection methods crucial for interpretation and improving the accuracy of survival models. We propose a novel variable selection method for a functional linear Cox model with multiple functional and scalar covariates measured at baseline. We utilize a spline-based semiparametric estimation approach for the functional coefficients and a group minimax concave type penalty (MCP), which effectively integrates smoothness and sparsity into the estimation of functional coefficients. An efficient group descent algorithm is used for optimization, and an automated procedure is provided to select optimal values of the smoothing and sparsity parameters. Through simulation studies, we demonstrate the method's ability to perform accurate variable selection and estimation. The method is applied to 2003-06 cohort of the National Health and Nutrition Examination Survey (NHANES) data, identifying the key temporally varying distributional patterns of physical activity and demographic predictors related to all-cause mortality. Our analysis sheds light on the intricate association between daily distributional patterns of physical activity and all-cause mortality among older US adults.

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arXiv2025

Screening for Diabetes Mellitus in the U.S. Population Using Neural Network Models and Complex Survey Designs

Complex survey designs are commonly employed in many medical cohorts. In such scenarios, developing case-specific predictive risk score models that reflect the unique characteristics of the study design is essential for minimizing selective biases in the statistical results. The objectives of this paper are to: (i) propose a general predictive framework for regression and classification using neural network (NN) modeling that incorporates survey weights into the estimation process; (ii) introduce an uncertainty quantification algorithm for model prediction tailored to data from complex survey designs; and (iii) apply this method to develop robust risk score models for assessing the risk of Diabetes Mellitus in the US population, utilizing data from the NHANES 2011-2014 cohort. The results indicate that models of varying complexity, each utilizing a different set of variables, demonstrate different discriminative power for predicting diabetes (with different economic cost), yet yield generalizable results at the population level. Although the focus is on diabetes, this NN predictive framework is adaptable for developing clinical models across a diverse range of diseases and medical cohorts. The software and data used in this paper are publicly available on GitHub.

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arXiv2024

Glucodensity Functional Profiles Outperform Traditional Continuous Glucose Monitoring Metrics

Continuous glucose monitoring (CGM) data has revolutionized the management of type 1 diabetes, particularly when integrated with insulin pumps to mitigate clinical events such as hypoglycemia. Recently, there has been growing interest in utilizing CGM devices in clinical studies involving healthy and diabetes populations. However, efficiently exploiting the high temporal resolution of CGM profiles remains a significant challenge. Numerous indices -- such as time-in-range metrics and glucose variability measures -- have been proposed, but evidence suggests these metrics overlook critical aspects of glucose dynamic homeostasis. As an alternative method, this paper explores the clinical value of glucodensity metrics in capturing glucose dynamics -- specifically the speed and acceleration of CGM time series -- as new biomarkers for predicting long-term glucose outcomes. Our results demonstrate significant information gains, exceeding 20\% in terms of adjusted $R^2$, in forecasting glycosylated hemoglobin (HbA1c) and fasting plasma glucose (FPG) at five and eight years from baseline AEGIS data, compared to traditional non-CGM and CGM glucose biomarkers. These findings underscore the importance of incorporating more complex CGM functional metrics, such as the glucodensity approach, to fully capture continuous glucose fluctuations across different time-scale resolutions.

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arXiv2024

Functional Time Transformation Model with Applications to Digital Health

The advent of wearable and sensor technologies now leads to functional predictors which are intrinsically infinite dimensional. While the existing approaches for functional data and survival outcomes lean on the well-established Cox model, the proportional hazard (PH) assumption might not always be suitable in real-world applications. Motivated by physiological signals encountered in digital medicine, we develop a more general and flexible functional time-transformation model for estimating the conditional survival function with both functional and scalar covariates. A partially functional regression model is used to directly model the survival time on the covariates through an unknown monotone transformation and a known error distribution. We use Bernstein polynomials to model the monotone transformation function and the smooth functional coefficients. A sieve method of maximum likelihood is employed for estimation. Numerical simulations illustrate a satisfactory performance of the proposed method in estimation and inference. We demonstrate the application of the proposed model through two case studies involving wearable data i) Understanding the association between diurnal physical activity pattern and all-cause mortality based on accelerometer data from the National Health and Nutrition Examination Survey (NHANES) 2011-2014 and ii) Modelling Time-to-Hypoglycemia events in a cohort of diabetic patients based on distributional representation of continuous glucose monitoring (CGM) data. The results provide important epidemiological insights into the direct association between survival times and the physiological signals and also exhibit superior predictive performance compared to traditional summary based biomarkers in the CGM study.

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arXiv2024

Conformal uncertainty quantification using kernel depth measures in separable Hilbert spaces

Depth measures have gained popularity in the statistical literature for defining level sets in complex data structures like multivariate data, functional data, and graphs. Despite their versatility, integrating depth measures into regression modeling for establishing prediction regions remains underexplored. To address this gap, we propose a novel method utilizing a model-free uncertainty quantification algorithm based on conditional depth measures and conditional kernel mean embeddings. This enables the creation of tailored prediction and tolerance regions in regression models handling complex statistical responses and predictors in separable Hilbert spaces. Our focus in this paper is exclusively on examples where the response is a functional data object. To enhance practicality, we introduce a conformal prediction algorithm, providing non-asymptotic guarantees in the derived prediction region. Additionally, we establish both conditional and unconditional consistency results and fast convergence rates in some special homoscedastic cases. We evaluate the model finite sample performance in extensive simulation studies with different function objects as probability distributions and functional data. Finally, we apply the approach in a digital health application related to physical activity, aiming to offer personalized recommendations in the US. population based on individuals' characteristics.

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arXiv2024

Personalized Imputation in metric spaces via conformal prediction: Applications in Predicting Diabetes Development with Continuous Glucose Monitoring Information

The challenge of handling missing data is widespread in modern data analysis, particularly during the preprocessing phase and in various inferential modeling tasks. Although numerous algorithms exist for imputing missing data, the assessment of imputation quality at the patient level often lacks personalized statistical approaches. Moreover, there is a scarcity of imputation methods for metric space based statistical objects. The aim of this paper is to introduce a novel two-step framework that comprises: (i) a imputation methods for statistical objects taking values in metrics spaces, and (ii) a criterion for personalizing imputation using conformal inference techniques. This work is motivated by the need to impute distributional functional representations of continuous glucose monitoring (CGM) data within the context of a longitudinal study on diabetes, where a significant fraction of patients do not have available CGM profiles. The importance of these methods is illustrated by evaluating the effectiveness of CGM data as new digital biomarkers to predict the time to diabetes onset in healthy populations. To address these scientific challenges, we propose: (i) a new regression algorithm for missing responses; (ii) novel conformal prediction algorithms tailored for metric spaces with a focus on density responses within the 2-Wasserstein geometry; (iii) a broadly applicable personalized imputation method criterion, designed to enhance both of the aforementioned strategies, yet valid across any statistical model and data structure. Our findings reveal that incorporating CGM data into diabetes time-to-event analysis, augmented with a novel personalization phase of imputation, significantly enhances predictive accuracy by over ten percent compared to traditional predictive models for time to diabetes.

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arXiv2024

Distributional outcome regression via quantile functions and its application to modelling continuously monitored heart rate and physical activity

Modern clinical and epidemiological studies widely employ wearables to record parallel streams of real-time data on human physiology and behavior. With recent advances in distributional data analysis, these high-frequency data are now often treated as distributional observations resulting in novel regression settings. Motivated by these modelling setups, we develop a distributional outcome regression via quantile functions (DORQF) that expands existing literature with three key contributions: i) handling both scalar and distributional predictors, ii) ensuring jointly monotone regression structure without enforcing monotonicity on individual functional regression coefficients, iii) providing statistical inference via asymptotic projection-based joint confidence bands and a statistical test of global significance to quantify uncertainty of the estimated functional regression coefficients. The method is motivated by and applied to Actiheart component of Baltimore Longitudinal Study of Aging that collected one week of minute-level heart rate (HR) and physical activity (PA) data on 781 older adults to gain deeper understanding of age-related changes in daily life heart rate reserve, defined as a distribution of daily HR, while accounting for daily distribution of physical activity, age, gender, and body composition. Intriguingly, the results provide novel insights in epidemiology of daily life heart rate reserve.

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arXiv2023

Multivariate Scalar on Multidimensional Distribution Regression

We develop a new method for multivariate scalar on multidimensional distribution regression. Traditional approaches typically analyze isolated univariate scalar outcomes or consider unidimensional distributional representations as predictors. However, these approaches are sub-optimal because: i) they fail to utilize the dependence between the distributional predictors: ii) neglect the correlation structure of the response. To overcome these limitations, we propose a multivariate distributional analysis framework that harnesses the power of multivariate density functions and multitask learning. We develop a computationally efficient semiparametric estimation method for modelling the effect of the latent joint density on multivariate response of interest. Additionally, we introduce a new conformal algorithm for quantifying the uncertainty of regression models with multivariate responses and distributional predictors, providing valuable insights into the conditional distribution of the response. We have validated the effectiveness of our proposed method through comprehensive numerical simulations, clearly demonstrating its superior performance compared to traditional methods. The application of the proposed method is demonstrated on tri-axial accelerometer data from the National Health and Nutrition Examination Survey (NHANES) 2011-2014 for modelling the association between cognitive scores across various domains and distributional representation of physical activity among older adult population. Our results highlight the advantages of the proposed approach, emphasizing the significance of incorporating complete spatial information derived from the accelerometer device.

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arXiv2023

Functional Principal Component Analysis for Continuous non-Gaussian, Truncated, and Discrete Functional Data

Mobile health studies often collect multiple within-day self-reported assessments of participants' behavior and well-being on different scales such as physical activity (continuous), pain levels (truncated), mood states (ordinal), and life events (binary). These assessments, when indexed by time of day, can be treated as functional data of different types - continuous, truncated, ordinal, and binary. We develop a functional principal component analysis that deals with all four types of functional data in a unified manner. It employs a semiparametric Gaussian copula model, assuming a generalized latent non-paranormal process as the underlying mechanism for these four types of functional data. We specify latent temporal dependence using a covariance estimated through Kendall's tau bridging method, incorporating smoothness during the bridging process. Simulation studies demonstrate the method's competitive performance under both dense and sparse sampling conditions. We then apply this approach to data from 497 participants in the National Institute of Mental Health Family Study of the Mood Disorder Spectrum to characterize within-day temporal patterns of mood differences among individuals with major mood disorder subtypes, including Major Depressive Disorder, Type 1, and Type 2 Bipolar Disorder.

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arXiv2023

Functional proportional hazards mixture cure model and its application to modelling the association between cancer mortality and physical activity in NHANES 2003-2006

We develop a functional proportional hazards mixture cure (FPHMC) model with scalar and functional covariates measured at the baseline. The mixture cure model, useful in studying populations with a cure fraction of a particular event of interest is extended to functional data. We employ the EM algorithm and develop a semiparametric penalized spline-based approach to estimate the dynamic functional coefficients of the incidence and the latency part. The proposed method is computationally efficient and simultaneously incorporates smoothness in the estimated functional coefficients via roughness penalty. Simulation studies illustrate a satisfactory performance of the proposed method in accurately estimating the model parameters and the baseline survival function. Finally, the clinical potential of the model is demonstrated in two real data examples that incorporate rich high-dimensional biomedical signals as functional covariates measured at the baseline and constitute novel domains to apply cure survival models in contemporary medical situations. In particular, we analyze i) minute-by-minute physical activity data from the National Health and Nutrition Examination Survey (NHANES) 2003-2006 to study the association between diurnal patterns of physical activity (PA) at baseline and all cancer mortality through 2019 while adjusting for other biological factors; ii) the impact of daily functional measures of disease severity collected in the intensive care unit on post ICU recovery and mortality event. Our findings provide novel epidemiological insights into the association between daily patterns of PA and cancer mortality. Software implementation and illustration of the proposed estimation method is provided in R.

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arXiv2022

Shape-constrained Estimation in Functional Regression with Bernstein Polynomials

Shape restrictions on functional regression coefficients such as non-negativity, monotonicity, convexity or concavity are often available in the form of a prior knowledge or required to maintain a structural consistency in functional regression models. A new estimation method is developed in shape-constrained functional regression models using Bernstein polynomials. Specifically, estimation approaches from nonparametric regression are extended to functional data, properly accounting for shape-constraints in a large class of functional regression models such as scalar-on-function regression (SOFR), function-on-scalar regression (FOSR), and function-on-function regression (FOFR). Theoretical results establish the asymptotic consistency of the constrained estimators under standard regularity conditions. A projection based approach provides point-wise asymptotic confidence intervals for the constrained estimators. A bootstrap test is developed facilitating testing of the shape constraints. Numerical analysis using simulations illustrate improvement in efficiency of the estimators from the use of the proposed method under shape constraints. Two applications include i) modeling a drug effect in a mental health study via shape-restricted FOSR and ii) modeling subject-specific quantile functions of accelerometry-estimated physical activity in the Baltimore Longitudinal Study of Aging (BLSA) as outcomes via shape-restricted quantile-function on scalar regression (QFOSR). R software implementation and illustration of the proposed estimation method and the test is provided.

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