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Main Authors: Vo, Duong H. T., Syed, Nelofer, Thorne, Thomas
Format: Preprint
Published: 2025
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Online Access:https://arxiv.org/abs/2503.05448
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author Vo, Duong H. T.
Syed, Nelofer
Thorne, Thomas
author_facet Vo, Duong H. T.
Syed, Nelofer
Thorne, Thomas
contents Graphical modeling is a widely used tool for analyzing conditional dependencies between variables and traditional methods may struggle to capture shared and distinct structures in multi-group or multi-condition settings. Joint graphical modeling (JGM) extends this framework by simultaneously estimating network structures across multiple related datasets, allowing for a deeper understanding of commonalities and differences. This capability is particularly valuable in fields such as genomics and neuroscience, where identifying variations in network topology can provide critical biological insights. Existing JGM methodologies largely fall into two categories: regularization-based approaches, which introduce additional penalties to enforce structured sparsity, and Bayesian frameworks, which incorporate prior knowledge to improve network inference. In this study, we explore an alternative method based on two-target linear covariance matrix shrinkage. Formula for optimal shrinkage intensities is proposed which leads to the development of JointStein framework. Performance of JointStein framework is proposed through simulation benchmarking which demonstrates its effectiveness for large-scale single-cell RNA sequencing (scRNA-seq) data analysis. Finally, we apply our approach to glioblastoma scRNA-seq data, uncovering dynamic shifts in T cell network structures across disease progression stages. The result highlights potential of JointStein framework in extracting biologically meaningful insights from high-dimensional data.
format Preprint
id arxiv_https___arxiv_org_abs_2503_05448
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle Joint graphical model estimation using Stein-type shrinkage for fast large scale network inference in scRNAseq data
Vo, Duong H. T.
Syed, Nelofer
Thorne, Thomas
Methodology
Molecular Networks
Quantitative Methods
Graphical modeling is a widely used tool for analyzing conditional dependencies between variables and traditional methods may struggle to capture shared and distinct structures in multi-group or multi-condition settings. Joint graphical modeling (JGM) extends this framework by simultaneously estimating network structures across multiple related datasets, allowing for a deeper understanding of commonalities and differences. This capability is particularly valuable in fields such as genomics and neuroscience, where identifying variations in network topology can provide critical biological insights. Existing JGM methodologies largely fall into two categories: regularization-based approaches, which introduce additional penalties to enforce structured sparsity, and Bayesian frameworks, which incorporate prior knowledge to improve network inference. In this study, we explore an alternative method based on two-target linear covariance matrix shrinkage. Formula for optimal shrinkage intensities is proposed which leads to the development of JointStein framework. Performance of JointStein framework is proposed through simulation benchmarking which demonstrates its effectiveness for large-scale single-cell RNA sequencing (scRNA-seq) data analysis. Finally, we apply our approach to glioblastoma scRNA-seq data, uncovering dynamic shifts in T cell network structures across disease progression stages. The result highlights potential of JointStein framework in extracting biologically meaningful insights from high-dimensional data.
title Joint graphical model estimation using Stein-type shrinkage for fast large scale network inference in scRNAseq data
topic Methodology
Molecular Networks
Quantitative Methods
url https://arxiv.org/abs/2503.05448