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用单细胞基因组学数据研究细胞的随机系统生物学。

Studying stochastic systems biology of the cell with single-cell genomics data.

机构信息

Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.

Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.

出版信息

Cell Syst. 2023 Oct 18;14(10):822-843.e22. doi: 10.1016/j.cels.2023.08.004. Epub 2023 Sep 25.

Abstract

Recent experimental developments in genome-wide RNA quantification hold considerable promise for systems biology. However, rigorously probing the biology of living cells requires a unified mathematical framework that accounts for single-molecule biological stochasticity in the context of technical variation associated with genomics assays. We review models for a variety of RNA transcription processes, as well as the encapsulation and library construction steps of microfluidics-based single-cell RNA sequencing, and present a framework to integrate these phenomena by the manipulation of generating functions. Finally, we use simulated scenarios and biological data to illustrate the implications and applications of the approach.

摘要

近年来,全基因组 RNA 定量方面的实验进展为系统生物学带来了巨大的希望。然而,要严格探究活细胞的生物学特性,则需要建立一个统一的数学框架,该框架需要考虑与基因组学测定相关的技术变化背景下单个分子的生物随机性。我们综述了各种 RNA 转录过程的模型,以及基于微流控的单细胞 RNA 测序的封装和文库构建步骤,并提出了通过生成函数的操作来整合这些现象的框架。最后,我们使用模拟场景和生物数据来说明该方法的意义和应用。

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