Department of Biochemistry, Stanford University, Stanford, CA, 94305, USA.
Department of Biomedical Data Science, Stanford University, Stanford, CA, 94305, USA.
Genome Biol. 2022 Oct 25;23(1):226. doi: 10.1186/s13059-022-02795-8.
RNA processing, including splicing and alternative polyadenylation, is crucial to gene function and regulation, but methods to detect RNA processing from single-cell RNA sequencing data are limited by reliance on pre-existing annotations, peak calling heuristics, and collapsing measurements by cell type. We introduce ReadZS, an annotation-free statistical approach to identify regulated RNA processing in single cells. ReadZS discovers cell type-specific RNA processing in human lung and conserved, developmentally regulated RNA processing in mammalian spermatogenesis-including global 3' UTR shortening in human spermatogenesis. ReadZS also discovers global 3' UTR lengthening in Arabidopsis development, highlighting the usefulness of this method in under-annotated transcriptomes.
RNA 加工,包括剪接和可变多聚腺苷酸化,对基因功能和调控至关重要,但从单细胞 RNA 测序数据中检测 RNA 加工的方法受到依赖于预先存在的注释、峰调用启发式和按细胞类型合并测量的限制。我们引入了 ReadZS,这是一种无注释的统计方法,用于识别单细胞中的受调控的 RNA 加工。ReadZS 在人类肺部中发现了细胞类型特异性的 RNA 加工,在哺乳动物精子发生中发现了保守的、发育调控的 RNA 加工,包括人类精子发生中的全局 3'UTR 缩短。ReadZS 还在拟南芥发育中发现了全局 3'UTR 延长,突出了这种方法在注释不足的转录组中的有用性。