Gene function revealed at the moment of stochastic gene silencing
Abstract Gene expression is a dynamic and stochastic process characterized by transcriptional bursting followed by periods of silence. Single-cell RNA sequencing (scRNA-seq) is a powerful tool to measure transcriptional bursting and silencing at the individual cell level. In this study, we introduce...
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| Format: | Article |
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Nature Portfolio
2025-01-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-07530-0 |
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| author | Shreyan Gupta James J. Cai |
| author_facet | Shreyan Gupta James J. Cai |
| author_sort | Shreyan Gupta |
| collection | DOAJ |
| description | Abstract Gene expression is a dynamic and stochastic process characterized by transcriptional bursting followed by periods of silence. Single-cell RNA sequencing (scRNA-seq) is a powerful tool to measure transcriptional bursting and silencing at the individual cell level. In this study, we introduce the single-cell Stochastic Gene Silencing (scSGS) method, which leverages the natural variability in single-cell gene expression to decipher gene function. For a target gene g under investigation, scSGS classifies cells into transcriptionally active (g+) and silenced (g-) samples. It then compares these cell samples to identify differentially expressed genes, referred to as SGS-responsive genes, which are used to infer the function of the target gene g. Analysis of real data demonstrates that scSGS can reveal regulatory relationships up- and downstream of target genes, circumventing the survivorship bias that often affects gene knockout and perturbation studies. scSGS thus offers an efficient approach for gene function prediction, with significant potential to reduce the use of genetically modified animals in gene function research. |
| format | Article |
| id | doaj-art-0310926a6cdd4c6696d2b5f988e2c314 |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-0310926a6cdd4c6696d2b5f988e2c3142025-02-09T12:50:39ZengNature PortfolioCommunications Biology2399-36422025-01-018111410.1038/s42003-025-07530-0Gene function revealed at the moment of stochastic gene silencingShreyan Gupta0James J. Cai1Department 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 UniversityAbstract Gene expression is a dynamic and stochastic process characterized by transcriptional bursting followed by periods of silence. Single-cell RNA sequencing (scRNA-seq) is a powerful tool to measure transcriptional bursting and silencing at the individual cell level. In this study, we introduce the single-cell Stochastic Gene Silencing (scSGS) method, which leverages the natural variability in single-cell gene expression to decipher gene function. For a target gene g under investigation, scSGS classifies cells into transcriptionally active (g+) and silenced (g-) samples. It then compares these cell samples to identify differentially expressed genes, referred to as SGS-responsive genes, which are used to infer the function of the target gene g. Analysis of real data demonstrates that scSGS can reveal regulatory relationships up- and downstream of target genes, circumventing the survivorship bias that often affects gene knockout and perturbation studies. scSGS thus offers an efficient approach for gene function prediction, with significant potential to reduce the use of genetically modified animals in gene function research.https://doi.org/10.1038/s42003-025-07530-0 |
| spellingShingle | Shreyan Gupta James J. Cai Gene function revealed at the moment of stochastic gene silencing Communications Biology |
| title | Gene function revealed at the moment of stochastic gene silencing |
| title_full | Gene function revealed at the moment of stochastic gene silencing |
| title_fullStr | Gene function revealed at the moment of stochastic gene silencing |
| title_full_unstemmed | Gene function revealed at the moment of stochastic gene silencing |
| title_short | Gene function revealed at the moment of stochastic gene silencing |
| title_sort | gene function revealed at the moment of stochastic gene silencing |
| url | https://doi.org/10.1038/s42003-025-07530-0 |
| work_keys_str_mv | AT shreyangupta genefunctionrevealedatthemomentofstochasticgenesilencing AT jamesjcai genefunctionrevealedatthemomentofstochasticgenesilencing |