UniTVelo: temporally unified RNA velocity reinforces single-cell trajectory inference.

UniTVelo: temporally unified RNA velocity reinforces single-cell trajectory inference.
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DOI:
10.1038/s41467-022-34188-7
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发表时间:
2022-11-03
影响因子:
16.6
通讯作者:
--
中科院分区:
综合性期刊1区
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单细胞RNA速度方法的突破为揭示细胞分化、状态转换和对扰动的反应的定向轨迹带来了诱人的希望。然而,现有的RNA速度方法经常被发现返回错误的结果,部分原因是模型违规或缺乏时间正则化。在这里,我们提出了UniTVelo,RNA速度的统计框架,通过灵活的转录活动模拟剪接和未剪接RNA的动态。独特的是,它还支持跨转录组的统一潜伏时间的推断。通过10个数据集,我们证明了UniTVelo在不同的生物系统中返回了预期的轨迹,包括造血分化以及那些动力学较弱或分支复杂的系统。RNA速度可以通过对稀疏未剪接RNA进行建模来检测分化方向性,但存在较高的估计误差。在这里,作者开发了一种名为UniTVelo的计算方法,通过引入统一的时间和自上而下的模型设计来加强速度估计。
The recent breakthrough of single-cell RNA velocity methods brings attractive promises to reveal directed trajectory on cell differentiation, states transition and response to perturbations. However, the existing RNA velocity methods are often found to return erroneous results, partly due to model violation or lack of temporal regularization. Here, we present UniTVelo, a statistical framework of RNA velocity that models the dynamics of spliced and unspliced RNAs via flexible transcription activities. Uniquely, it also supports the inference of a unified latent time across the transcriptome. With ten datasets, we demonstrate that UniTVelo returns the expected trajectory in different biological systems, including hematopoietic differentiation and those even with weak kinetics or complex branches. RNA velocity can detect the differentiation directionality by modelling sparse unspliced RNAs, but suffers from high estimation errors. Here, the authors develop a computational method called UniTVelo to reinforce the velocity estimation by introducing a unified time and a top-down model design.
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