bakR: uncovering differential RNA synthesis and degradation kinetics transcriptome-wide with Bayesian hierarchical modeling.

bakR: uncovering differential RNA synthesis and degradation kinetics transcriptome-wide with Bayesian hierarchical modeling.
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DOI:
10.1261/rna.079451.122
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发表时间:
2023-07
期刊:
RNA (New York, N.Y.)
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RNA测序数据的差异表达分析(RNA-seq)可以识别细胞RNA水平的变化,但提供的有关这种变化的动力学机制的信息有限。核苷酸重新编码RNA-seq方法(NR-seq;例如,TimeLapse-seq、SLAM-seq等)解决了这一缺点,并且是广泛使用的方法来鉴定RNA合成和降解动力学的变化。虽然在用户友好的软件中实现了高级统计模型(例如,DESeq 2)已经确保了差异表达分析的统计学严谨性,但是不存在促进用NR-seq进行差异动力学分析的这样的工具。在这里,我们报告的发展贝叶斯分析的动力学的RNA(bakR;),R包,以满足这一需求。bakR依赖于NR-seq数据的贝叶斯分层建模,通过在转录本之间共享信息来增加统计能力。模拟数据的分析证实,bakR实现的分层模型优于尝试用现有模型分析微分动力学。bakR还发现了真实的NR-seq数据集中的生物信号,并提供了对现有数据集的改进分析。这项工作确立了bakR作为识别差异RNA合成和降解动力学的重要工具。
Differential expression analysis of RNA sequencing (RNA-seq) data can identify changes in cellular RNA levels, but provides limited information about the kinetic mechanisms underlying such changes. Nucleotide recoding RNA-seq methods (NR-seq; e.g., TimeLapse-seq, SLAM-seq, etc.) address this shortcoming and are widely used approaches to identify changes in RNA synthesis and degradation kinetics. While advanced statistical models implemented in user-friendly software (e.g., DESeq2) have ensured the statistical rigor of differential expression analyses, no such tools that facilitate differential kinetic analysis with NR-seq exist. Here, we report the development of Bayesian analysis of the kinetics of RNA (bakR; ), an R package to address this need. bakR relies on Bayesian hierarchical modeling of NR-seq data to increase statistical power by sharing information across transcripts. Analyses of simulated data confirmed that bakR implementations of the hierarchical model outperform attempts to analyze differential kinetics with existing models. bakR also uncovers biological signals in real NR-seq data sets and provides improved analyses of existing data sets. This work establishes bakR as an important tool for identifying differential RNA synthesis and degradation kinetics.
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