Department of Biostatistics, Brown University, Providence, RI, USA.
Center for Statistical Sciences, Brown University, Providence, RI, USA.
Bioinformatics. 2018 Oct 1;34(19):3340-3348. doi: 10.1093/bioinformatics/bty329.
Single-cell RNA-sequencing (scRNA-seq) has brought the study of the transcriptome to higher resolution and makes it possible for scientists to provide answers with more clarity to the question of 'differential expression'. However, most computational methods still stick with the old mentality of viewing differential expression as a simple 'up or down' phenomenon. We advocate that we should fully embrace the features of single cell data, which allows us to observe binary (from Off to On) as well as continuous (the amount of expression) regulations.
We develop a method, termed SC2P, that first identifies the phase of expression a gene is in, by taking into account of both cell- and gene-specific contexts, in a model-based and data-driven fashion. We then identify two forms of transcription regulation: phase transition, and magnitude tuning. We demonstrate that compared with existing methods, SC2P provides substantial improvement in sensitivity without sacrificing the control of false discovery, as well as better robustness. Furthermore, the analysis provides better interpretation of the nature of regulation types in different genes.
SC2P is implemented as an open source R package publicly available at https://github.com/haowulab/SC2P.
Supplementary data are available at Bioinformatics online.
单细胞 RNA 测序 (scRNA-seq) 将转录组的研究推向了更高的分辨率,使科学家能够更清晰地回答“差异表达”的问题。然而,大多数计算方法仍然坚持将差异表达视为简单的“上调或下调”现象的旧观念。我们主张我们应该充分利用单细胞数据的特征,这使我们能够观察到二元(从关闭到开启)和连续(表达量)的调控。
我们开发了一种称为 SC2P 的方法,该方法首先通过基于模型和数据驱动的方式,同时考虑细胞和基因特异性的上下文,确定基因表达所处的阶段。然后,我们确定了两种转录调控形式:相位转变和幅度调谐。我们证明,与现有方法相比,SC2P 在不牺牲假发现控制的情况下,在灵敏度上有了显著提高,并且具有更好的稳健性。此外,该分析提供了对不同基因中调控类型本质的更好解释。
SC2P 作为一个开源 R 包实现,可在 https://github.com/haowulab/SC2P 上公开获取。
补充数据可在生物信息学在线获取。