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Thierry Chekouo

Publications and source records attributed to Thierry Chekouo.

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BayesClint: Bayesian Multi-Scale Clustering and Multi-Sample Integration With Feature Selection for Spatial Transcriptomics Data

Recent advances in spatial transcriptomics have enabled researchers to profile gene expression at the single-cell spatial resolution, often for multiple tissue samples in a single study. This high-dimensional molecular profile for each cell can be used to sort cells into cell types with distinct functions, or segment the tissue into biologically relevant spatial domains. Although many non-spatial and spatial clustering methods have been developed to cluster these cells into cell types or spatial domains, most have two main limitations: first, they perform dimension reduction and clustering separately; second, they cluster cells at a single scale, rather than treating cell type and spatial domain clustering as distinct tasks at two different scales. To overcome these limitations, we propose BayesClint, a Bayesian method that simultaneously performs factor analysis and spatial clustering on multiple samples, where the clustering is done jointly at the single-cell and tissue regional scale. To increase interpretability, we employ a feature selection mechanism within the estimation of the sparse factor loadings matrix, which detects active genes and differentially expressed genes that discriminate between cell type clusters. We illustrate the advantages of the method over alternative state-of-the-art approaches through simulation studies and two real data applications.

stat.ME

Sparse Functional Singular Value Decomposition for Biclustering and Triclustering Longitudinal Data

Identifying subtypes of complex conditions, such as Inflammatory Bowel Disease (IBD), often requires capturing latent patterns in longitudinal omics data. However, these data are typically high-dimensional, sparsely sampled, and irregularly observed over time, posing substantial challenges for conventional (bi)clustering and functional data analysis methods. We propose Tri-SfSVD, a unified sparse functional Singular Value Decomposition framework for discovering biclusters and triclusters in longitudinal data. Unlike existing functional biclustering methods that rely on ad hoc imputation or enforce restrictive shape-homogeneity assumptions, Tri-SfSVD integrates continuous trajectory estimation with simultaneous subject, feature, and temporal selection within a single optimization framework. By imposing sparse penalties across subjects, variables, and temporal subregions, the proposed method works directly on observed data to uncover localized structures at the subject, subject-feature, and subject-feature-time levels. Extensive simulations demonstrate that Tri-SfSVD outperforms existing approaches in high-dimensional settings. Applied to IBD multi-omics data, the method identified three biclusters linking sample clusters with distinct IBD-related clinical characteristics to microbial pathway groups associated with specific bacterial taxa, providing interpretable subject-pathway associations for characterizing disease heterogeneity. Applied to multi-channel EEG data, the method identified three triclusters linking sample clusters with distinct alcohol-related phenotypes to localized brain activity patterns, including subgroup differences separated by temporal subregions within the same spatial region.

stat.ML

Supervised Integrative Biclustering with applications to Alzheimer's Disease

Multiple types or views of data (e.g. genetics, proteomics) measured on the same set of individuals are now popularly generated in many biomedical studies. A particular interest might be the detection of sample subgroups (e.g. subtypes of disease) characterized by specific groups of variables. Biclustering methods are well-suited for this problem since they can group samples and variables simultaneously. However, most existing biclustering methods cannot guarantee that the detected sample clusters are clinically meaningful and related to a clinical outcome because they independently identify biclusters and associate sample clusters with a clinical outcome. Additionally, these methods have been developed for continuous data when integrating data from different views and do not allow for a mixture of data distributions. We propose a new formulation of biclustering and prediction method for multi-view data from different distributions that enhances our ability to identify clinically meaningful biclusters by incorporating a clinical outcome. Sample clusters are defined based on an adaptively chosen subset of variables and their association with a clinical outcome. We use extensive simulations to showcase the effectiveness of our proposed method in comparison to existing methods. Real-world applications using lipidomics, imaging, and cognitive data on Alzheimer's disease(AD) identified biclusters with significant cognitive differences that other methods missed. The distinct lipid categories and brain regions characterizing the biclusters suggest potential new insights into pathology of AD.

stat.ME

A Bayesian Integrative Mixed Modeling Framework for Analysis of the Adolescent Brain and Cognitive Development Study

Integrating high-dimensional, heterogeneous data from multi-site cohort studies with complex hierarchical structures poses significant feature selection and prediction challenges. We extend the Bayesian Integrative Analysis and Prediction (BIP) framework to enable simultaneous feature selection and outcome modeling in data of nested hierarchical structure. We apply the proposed Bayesian Integrative Mixed Modeling (BIPmixed) framework to the Adolescent Brain Cognitive Development (ABCD) Study, leveraging multi-view data, including structural and functional MRI and early life adversity (ELA) metrics, to identify relevant features and predict the behavioral outcome. BIPmixed incorporates 2-level nested random effects, to enhance interpretability and make predictions in hierarchical data settings. Simulation studies illustrate BIPmixed's robustness in distinct random effect settings, highlighting its use for complex study designs. Our findings suggest that BIPmixed effectively integrates multi-view data while accounting for nested sampling, making it a valuable tool for analyzing large-scale studies with hierarchical data.

stat.ME

Bayesian variable selection using an informed reversible jump in imaging genetics: an application to schizophrenia

From a practical perspective, proposals are one of the main bottleneck for any Markov Chain Monte Carlo (MCMC) algorithm. This paper suggests a novel data driven or informed proposal for reversible jump MCMC for Bayesian variable selection in the context of predictive risk assessment for schizophrenia based on imaging genetic data. Given functional Magnetic Resonance Image and Single Nucleotide Polymorphisms information of healthy and people diagnosed with schizophrenia, we use a Bayesian probit model to select discriminating variables for inferential purposes, while to estimate the predictive risk, the most promising models are combined using a Bayesian model averaging scheme.

stat.AP

Broken Adaptive Ridge Method for Variable Selection in Generalized Partly Linear Models with Application to the Coronary Artery Disease Data

Motivated by the CATHGEN data, we develop a new statistical learning method for simultaneous variable selection and parameter estimation under the context of generalized partly linear models for data with high-dimensional covariates. The method is referred to as the broken adaptive ridge (BAR) estimator, which is an approximation of the $L_0$-penalized regression by iteratively performing reweighted squared $L_2$-penalized regression. The generalized partly linear model extends the generalized linear model by including a non-parametric component to construct a flexible model for modeling various types of covariate effects. We employ the Bernstein polynomials as the sieve space to approximate the non-parametric functions so that our method can be implemented easily using the existing R packages. Extensive simulation studies suggest that the proposed method performs better than other commonly used penalty-based variable selection methods. We apply the method to the CATHGEN data with a binary response from a coronary artery disease study, which motivated our research, and obtained new findings in both high-dimensional genetic and low-dimensional non-genetic covariates.

stat.ME

Bayesian Integrative Analysis and Prediction with Application to Atherosclerosis Cardiovascular Disease

Cardiovascular diseases (CVD), including atherosclerosis CVD (ASCVD), are multifactorial diseases that present a major economic and social burden worldwide. Tremendous efforts have been made to understand traditional risk factors for ASCVD, but these risk factors account for only about half of all cases of ASCVD. It remains a critical need to identify nontraditional risk factors (e.g., genetic variants, genes) contributing to ASCVD. Further, incorporating functional knowledge in prediction models have the potential to reveal pathways associated with disease risk. We propose Bayesian hierarchical factor analysis models that associate multiple omics data, predict a clinical outcome, allow for prior functional information, and can accommodate clinical covariates. The models, motivated by available data and the need for other risk factors of ASCVD, are used for the integrative analysis of clinical, demographic, and multi-omics data to identify genetic variants, genes, and gene pathways potentially contributing to 10-year ASCVD risk in healthy adults. Our findings revealed several genetic variants, genes and gene pathways that were highly associated with ASCVD risk. Interestingly, some of these have been implicated in CVD risk. The others could be explored for their potential roles in CVD. Our findings underscore the merit in joint association and prediction models.

stat.ME

The Gibbs-plaid biclustering model

We propose and develop a Bayesian plaid model for biclustering that accounts for the prior dependency between genes (and/or conditions) through a stochastic relational graph. This work is motivated by the need for improved understanding of the molecular mechanisms of human diseases for which effective drugs are lacking, and based on the extensive raw data available through gene expression profiling. We model the prior dependency information from biological knowledge gathered from gene ontologies. Our model, the Gibbs-plaid model, assumes that the relational graph is governed by a Gibbs random field. To estimate the posterior distribution of the bicluster membership labels, we develop a stochastic algorithm that is partly based on the Wang-Landau flat-histogram algorithm. We apply our method to a gene expression database created from the study of retinal detachment, with the aim of confirming known or finding novel subnetworks of proteins associated with this disorder.

stat.AP