arXiv subjects

Noirrit Kiran Chandra

Publications and source records attributed to Noirrit Kiran Chandra.

8 recordsLinked to original sources

arXiv2025

Monitoring Adverse Events Through Bayesian Nonparametric Clustering Across Studies

We introduce a Bayesian nonparametric inference approach for aggregate adverse event (AE) monitoring across studies. The proposed model seamlessly integrates external data from historical trials to define a relevant background rate and accommodates varying levels of covariate granularity (ranging from patient-level details to study-level aggregated summary data). Inference is based on a covariate-dependent product partition model (PPMx). A central element of the model is the ability to group experimental units with similar profiles. We introduce a pairwise similarity measure, with which we set up a random partition of experimental units with comparable covariate profiles, thereby improving the precision of AE rate estimation. Importantly, the proposed framework supports real-time safety monitoring under blinding with a seamless transition to unblinded analyses when indicated. Using one case study and simulation studies, we demonstrate the model's ability to detect safety signals and assess risk under diverse trial scenarios.

stat.ME↗

arXiv2024

Inferring Covariance Structure from Multiple Data Sources via Subspace Factor Analysis

Factor analysis provides a canonical framework for imposing lower-dimensional structure such as sparse covariance in high-dimensional data. High-dimensional data on the same set of variables are often collected under different conditions, for instance in reproducing studies across research groups. In such cases, it is natural to seek to learn the shared versus condition-specific structure. Existing hierarchical extensions of factor analysis have been proposed, but face practical issues including identifiability problems. To address these shortcomings, we propose a class of SUbspace Factor Analysis (SUFA) models, which characterize variation across groups at the level of a lower-dimensional subspace. We prove that the proposed class of SUFA models lead to identifiability of the shared versus group-specific components of the covariance, and study their posterior contraction properties. Taking a Bayesian approach, these contributions are developed alongside efficient posterior computation algorithms. Our sampler fully integrates out latent variables, is easily parallelizable and has complexity that does not depend on sample size. We illustrate the methods through application to integration of multiple gene expression datasets relevant to immunology.

stat.ME↗

arXiv2023

A Sparse Factor Model for Clustering High-Dimensional Longitudinal Data

Recent advances in engineering technologies have enabled the collection of a large number of longitudinal features. This wealth of information presents unique opportunities for researchers to investigate the complex nature of diseases and uncover underlying disease mechanisms. However, analyzing such kind of data can be difficult due to its high dimensionality, heterogeneity and computational challenges. In this paper, we propose a Bayesian nonparametric mixture model for clustering high-dimensional mixed-type (e.g., continuous, discrete and categorical) longitudinal features. We employ a sparse factor model on the joint distribution of random effects and the key idea is to induce clustering at the latent factor level instead of the original data to escape the curse of dimensionality. The number of clusters is estimated through a Dirichlet process prior. An efficient Gibbs sampler is developed to estimate the posterior distribution of the model parameters. Analysis of real and simulated data is presented and discussed. Our study demonstrates that the proposed model serves as a useful analytical tool for clustering high-dimensional longitudinal data.

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arXiv2023

Bayesian Nonparametric Common Atoms Regression for Generating Synthetic Controls in Clinical Trials

The availability of electronic health records (EHR) has opened opportunities to supplement increasingly expensive and difficult to carry out randomized controlled trials (RCT) with evidence from readily available real world data. In this paper, we use EHR data to construct synthetic control arms for treatment-only single arm trials. We propose a novel nonparametric Bayesian common atoms mixture model that allows us to find equivalent population strata in the EHR and the treatment arm and then resample the EHR data to create equivalent patient populations under both the single arm trial and the resampled EHR. Resampling is implemented via a density-free importance sampling scheme. Using the synthetic control arm, inference for the treatment effect can then be carried out using any method available for RCTs. Alternatively the proposed nonparametric Bayesian model allows straightforward model-based inference. In simulation experiments, the proposed method exhibits higher power than alternative methods in detecting treatment effects, specifically for non-linear response functions. We apply the method to supplement single arm treatment-only glioblastoma studies with a synthetic control arm based on historical trials.

stat.ME↗

arXiv2022

Escaping the curse of dimensionality in Bayesian model based clustering

Bayesian mixture models are widely used for clustering of high-dimensional data with appropriate uncertainty quantification. However, as the dimension of the observations increases, posterior inference often tends to favor too many or too few clusters. This article explains this behavior by studying the random partition posterior in a non-standard setting with a fixed sample size and increasing data dimensionality. We provide conditions under which the finite sample posterior tends to either assign every observation to a different cluster or all observations to the same cluster as the dimension grows. Interestingly, the conditions do not depend on the choice of clustering prior, as long as all possible partitions of observations into clusters have positive prior probabilities, and hold irrespective of the true data-generating model. We then propose a class of latent mixtures for Bayesian clustering (Lamb) on a set of low-dimensional latent variables inducing a partition on the observed data. The model is amenable to scalable posterior inference and we show that it can avoid the pitfalls of high-dimensionality under mild assumptions. The proposed approach is shown to have good performance in simulation studies and an application to inferring cell types based on scRNAseq.

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arXiv2022

Bayesian Scalable Precision Factor Analysis for Massive Sparse Gaussian Graphical Models

We propose a novel approach to estimating the precision matrix of multivariate Gaussian data that relies on decomposing them into a low-rank and a diagonal component. Such decompositions are very popular for modeling large covariance matrices as they admit a latent factor based representation that allows easy inference. The same is however not true for precision matrices due to the lack of computationally convenient representations which restricts inference to low-to-moderate dimensional problems. We address this remarkable gap in the literature by building on a latent variable representation for such decomposition for precision matrices. The construction leads to an efficient Gibbs sampler that scales very well to high-dimensional problems far beyond the limits of the current state-of-the-art. The ability to efficiently explore the full posterior space also allows the model uncertainty to be easily assessed. The decomposition crucially additionally allows us to adapt sparsity inducing priors to shrink the insignificant entries of the precision matrix toward zero, making the approach adaptable to high-dimensional small-sample-size sparse settings. Exact zeros in the matrix encoding the underlying conditional independence graph are then determined via a novel posterior false discovery rate control procedure. A near minimax optimal posterior concentration rate for estimating precision matrices is attained by our method under mild regularity assumptions. We evaluate the method's empirical performance through synthetic experiments and illustrate its practical utility in data sets from two different application domains.

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arXiv2020

High-dimensional Asymptotic Theory of Bayesian Multiple Testing Procedures Under General Dependent Setup and Possible Misspecification

In this article, we investigate the asymptotic properties of Bayesian multiple testing procedures under general dependent setup, when the sample size and the number of hypotheses both tend to infinity. Specifically, we investigate strong consistency of the procedures and asymptotic properties of different versions of false discovery and false non-discovery rates under the high dimensional setup. We particularly focus on a novel Bayesian non-marginal multiple testing procedure and its associated error rates in this regard. Our results show that the asymptotic convergence rates of the error rates are directly associated with the Kullback-Leibler divergence from the true model, and the results hold even when the postulated class of models is misspecified. For illustration of our high-dimensional asymptotic theory, we consider a Bayesian variable selection problem in a time-varying covariate selection framework, with autoregressive response variables. We particularly focus on the setup where the number of hypotheses increases at a faster rate compared to the sample size, which is the so-called ultra-high dimensional situation.

math.ST↗

arXiv2018

A Novel Bayesian Multiple Testing Approach to Deregulated miRNA Discovery Harnessing Positional Clustering

MicroRNAs (miRNAs) are small non-coding RNAs that function as regulators of gene expression. In recent years, there has been a tremendous and growing interest among researchers to investigate the role of miRNAs in normal cellular as well as in disease processes. Thus to investigate the role of miRNAs in oral cancer, we analyse the expression levels of miRNAs to identify miRNAs with statistically significant differential expression in cancer tissues. In this article, we propose a novel Bayesian hierarchical model of miRNA expression data. Compelling evidences have demonstrated that the transcription process of miRNAs in human genome is a latent process instrumental for the observed expression levels. We take into account positional clustering of the miRNAs in the analysis and model the latent transcription phenomenon nonparametrically by an appropriate Gaussian process. For the testing purpose we employ a novel Bayesian multiple testing method where we mainly focus on utilizing the dependence structure between the hypotheses for better results, while also ensuring optimality in many respects. Indeed, our non-marginal method yielded results in accordance with the underlying scientific knowledge which are found to be missed by the very popular Benjamini-Hochberg method.

stat.AP↗