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

Cell systems Pub Date : 2023-10-18 Epub Date: 2023-09-25 DOI:10.1016/j.cels.2023.08.004
Gennady Gorin, John J Vastola, Lior Pachter
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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.

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利用单细胞基因组学数据研究细胞的随机系统生物学。
全基因组RNA定量的最新实验进展对系统生物学具有相当大的前景。然而,严格探索活细胞的生物学需要一个统一的数学框架,该框架在与基因组学分析相关的技术变异的背景下解释单分子生物随机性。我们回顾了各种RNA转录过程的模型,以及基于微流体的单细胞RNA测序的封装和文库构建步骤,并提出了一个通过操纵生成函数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含义和应用。
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