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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Bibliographic Details
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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Summary: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.
ISSN:2056-7189