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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。

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

作者信息

Gorin Gennady, Vastola John J, Pachter Lior

机构信息

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

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

出版信息

bioRxiv. 2023 May 29:2023.05.17.541250. doi: 10.1101/2023.05.17.541250.

DOI:10.1101/2023.05.17.541250
PMID:37292934
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10245677/
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

全基因组RNA定量方面的最新实验进展为系统生物学带来了巨大希望。然而,要严格探究活细胞的生物学特性,需要一个统一的数学框架,该框架要在与基因组学检测相关的技术变异背景下考虑单分子生物随机性。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,并提出了一个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学数据来说明该方法的意义和应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2fe/10245677/0cdff71955dc/nihpp-2023.05.17.541250v2-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2fe/10245677/4553a1cf9335/nihpp-2023.05.17.541250v2-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2fe/10245677/d2e0fab0b98e/nihpp-2023.05.17.541250v2-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2fe/10245677/f29f6393d65c/nihpp-2023.05.17.541250v2-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2fe/10245677/aefd60d4d256/nihpp-2023.05.17.541250v2-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2fe/10245677/0cdff71955dc/nihpp-2023.05.17.541250v2-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2fe/10245677/4553a1cf9335/nihpp-2023.05.17.541250v2-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2fe/10245677/d2e0fab0b98e/nihpp-2023.05.17.541250v2-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2fe/10245677/f29f6393d65c/nihpp-2023.05.17.541250v2-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2fe/10245677/aefd60d4d256/nihpp-2023.05.17.541250v2-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2fe/10245677/0cdff71955dc/nihpp-2023.05.17.541250v2-f0005.jpg

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本文引用的文献

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Biophysical modeling with variational autoencoders for bimodal, single-cell RNA sequencing data.基于变分自动编码器的双模态单细胞 RNA 测序数据的生物物理建模。
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Spectral neural approximations for models of transcriptional dynamics.转录动力学模型的谱神经逼近。
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Characterization and decontamination of background noise in droplet-based single-cell protein expression data with DecontPro.
利用 DecontPro 对基于液滴的单细胞蛋白质表达数据中的背景噪声进行特征描述和清除。
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Pumping the brakes on RNA velocity by understanding and interpreting RNA velocity estimates.通过理解和解释 RNA 速度估计来减缓 RNA 速度。
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Modelling capture efficiency of single-cell RNA-sequencing data improves inference of transcriptome-wide burst kinetics.单细胞 RNA 测序数据的捕获效率建模可提高对转录组范围爆发动力学的推断。
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Interpretable and tractable models of transcriptional noise for the rational design of single-molecule quantification experiments.可解释且易于处理的转录噪声模型,用于合理设计单分子定量实验。
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