Exploring cell-to-cell variability and functional insights through differentially variable gene analysis

Abstract Single-cell RNA sequencing (scRNA-seq) has revolutionized our understanding of cellular variability by capturing gene expression profiles of individual cells. The importance of cell-to-cell variability in determining and shaping cell function has been widely appreciated. Nevertheless, diffe...

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Main Authors: Victoria Gatlin, Shreyan Gupta, Selim Romero, Robert S. Chapkin, James J. Cai
Format: Article
Language:English
Published: Nature Portfolio 2025-03-01
Series:npj Systems Biology and Applications
Online Access:https://doi.org/10.1038/s41540-025-00507-z
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author Victoria Gatlin
Shreyan Gupta
Selim Romero
Robert S. Chapkin
James J. Cai
author_facet Victoria Gatlin
Shreyan Gupta
Selim Romero
Robert S. Chapkin
James J. Cai
author_sort Victoria Gatlin
collection DOAJ
description Abstract Single-cell RNA sequencing (scRNA-seq) has revolutionized our understanding of cellular variability by capturing gene expression profiles of individual cells. The importance of cell-to-cell variability in determining and shaping cell function has been widely appreciated. Nevertheless, differential expression (DE) analysis remains a cornerstone method in analytical practice. Current computational analyses overlook the rich information encoded by variability within the single-cell gene expression data by focusing exclusively on mean expression. To offer a deeper understanding of cellular systems, there is a need for approaches to assess data variability rather than just the mean. Here we present spline-DV, a statistical framework for differential variability (DV) analysis using scRNA-seq data. The spline-DV method identifies genes exhibiting significantly increased or decreased expression variability among cells derived from two experimental conditions. Case studies show that DV genes identified using spline-DV are representative and functionally relevant to tested cellular conditions, including obesity, fibrosis, and cancer.
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spelling doaj-art-313353dfb0d14d848f8f0cf0f447258b2025-08-20T02:52:17ZengNature Portfolionpj Systems Biology and Applications2056-71892025-03-0111111110.1038/s41540-025-00507-zExploring cell-to-cell variability and functional insights through differentially variable gene analysisVictoria Gatlin0Shreyan Gupta1Selim Romero2Robert S. Chapkin3James J. Cai4Department of Veterinary Integrative Biosciences, School of Veterinary Medicine and Biomedical Sciences, Texas A&M UniversityDepartment of Veterinary Integrative Biosciences, School of Veterinary Medicine and Biomedical Sciences, Texas A&M UniversityDepartment of Veterinary Integrative Biosciences, School of Veterinary Medicine and Biomedical Sciences, Texas A&M UniversityCPRIT Single Cell Data Science Core, Texas A&M UniversityDepartment of Veterinary Integrative Biosciences, School of Veterinary Medicine and Biomedical Sciences, Texas A&M UniversityAbstract Single-cell RNA sequencing (scRNA-seq) has revolutionized our understanding of cellular variability by capturing gene expression profiles of individual cells. The importance of cell-to-cell variability in determining and shaping cell function has been widely appreciated. Nevertheless, differential expression (DE) analysis remains a cornerstone method in analytical practice. Current computational analyses overlook the rich information encoded by variability within the single-cell gene expression data by focusing exclusively on mean expression. To offer a deeper understanding of cellular systems, there is a need for approaches to assess data variability rather than just the mean. Here we present spline-DV, a statistical framework for differential variability (DV) analysis using scRNA-seq data. The spline-DV method identifies genes exhibiting significantly increased or decreased expression variability among cells derived from two experimental conditions. Case studies show that DV genes identified using spline-DV are representative and functionally relevant to tested cellular conditions, including obesity, fibrosis, and cancer.https://doi.org/10.1038/s41540-025-00507-z
spellingShingle Victoria Gatlin
Shreyan Gupta
Selim Romero
Robert S. Chapkin
James J. Cai
Exploring cell-to-cell variability and functional insights through differentially variable gene analysis
npj Systems Biology and Applications
title Exploring cell-to-cell variability and functional insights through differentially variable gene analysis
title_full Exploring cell-to-cell variability and functional insights through differentially variable gene analysis
title_fullStr Exploring cell-to-cell variability and functional insights through differentially variable gene analysis
title_full_unstemmed Exploring cell-to-cell variability and functional insights through differentially variable gene analysis
title_short Exploring cell-to-cell variability and functional insights through differentially variable gene analysis
title_sort exploring cell to cell variability and functional insights through differentially variable gene analysis
url https://doi.org/10.1038/s41540-025-00507-z
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