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

Victoria Gatlin, Shreyan Gupta, Selim Romero, Robert S Chapkin, James J Cai
Author Information
  1. Victoria Gatlin: Department of Veterinary Integrative Biosciences, School of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, 77843, USA. ORCID
  2. Shreyan Gupta: Department of Veterinary Integrative Biosciences, School of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, 77843, USA. ORCID
  3. Selim Romero: Department of Veterinary Integrative Biosciences, School of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, 77843, USA.
  4. Robert S Chapkin: CPRIT Single Cell Data Science Core, Texas A&M University, College Station, TX, 77843, USA.
  5. James J Cai: Department of Veterinary Integrative Biosciences, School of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, 77843, USA. jcai@tamu.edu. ORCID

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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Grants

  1. GW200026/U.S. Department of Defense (United States Department of Defense)
  2. P30 ES029067/NIEHS NIH HHS
  3. RP230204/Cancer Prevention and Research Institute of Texas (Cancer Prevention Research Institute of Texas)
  4. RP230204/Cancer Prevention and Research Institute of Texas (Cancer Prevention Research Institute of Texas)

MeSH Term

Single-Cell Analysis
Humans
Computational Biology
Gene Expression Profiling
Sequence Analysis, RNA
Animals
Transcriptome
Algorithms

Word Cloud

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