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Updated: Sep 12, 2025

Analyzing Multifactorial RNA-Seq Experiments with DiCoExpress
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scCOSMIX: A Mixed-Effects Framework for Differential Coexpression and Transcriptional Interactions Modeling in

Anderson Bussing1, Giampiero Marra2, Daping Fan3

  • 1Department of Statistics, University of South Carolina, Columbia, South Carolina, USA.

Statistics in Medicine
|August 7, 2025
PubMed
Summary
This summary is machine-generated.

We developed scCOSMiX, a new statistical framework to analyze gene interactions in single-cell RNA sequencing (scRNA-seq) data. This method accounts for individual patient data, improving the study of dynamic gene expression changes.

Keywords:
Differential co‐expressionhierarchical study designmixed effectssingle‐cell RNA‐seqzero‐inflated copula model

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Area of Science:

  • Genomics
  • Bioinformatics
  • Computational Biology

Background:

  • Single-cell RNA sequencing (scRNA-seq) offers high-resolution gene expression data.
  • Understanding dynamic gene-gene interactions is crucial for cellular processes.
  • Existing methods struggle with the hierarchical structure of multi-subject scRNA-seq data.

Purpose of the Study:

  • To introduce scCOSMiX, a novel mixed-effects framework for differential co-expression analysis in scRNA-seq.
  • To address the challenge of cell-cell correlation within subjects in scRNA-seq data.
  • To enable robust modeling of dynamic gene interactions in complex experimental designs.

Main Methods:

  • Developed a copula-based mixed-effects framework (scCOSMiX).
  • Incorporated subject-level random effects to account for intra-individual cell correlations.
  • Modeled zero-inflation, marginal, and association parameters as functions of covariates.

Main Results:

  • scCOSMiX demonstrated superior performance in simulation studies compared to existing methods.
  • The framework effectively models conditional co-expression changes.
  • Applicability shown across diverse scRNA-seq protocols (droplet and plate-based).

Conclusions:

  • scCOSMiX provides a robust approach for analyzing dynamic gene interactions in scRNA-seq data.
  • The method accurately handles the hierarchical nature of multi-subject experiments.
  • This framework enhances the systematic study of gene-gene relationships at single-cell resolution.