MRC Biostatistics Unit, School of Clinical Medicine, University of Cambridge, Cambridge, UK.
Alan Turing Institute, London, UK.
Bioinformatics. 2019 Feb 15;35(4):611-618. doi: 10.1093/bioinformatics/bty664.
MOTIVATION: A number of pseudotime methods have provided point estimates of the ordering of cells for scRNA-seq data. A still limited number of methods also model the uncertainty of the pseudotime estimate. However, there is still a need for a method to sample from complicated and multi-modal distributions of orders, and to estimate changes in the amount of the uncertainty of the order during the course of a biological development, as this can support the selection of suitable cells for the clustering of genes or for network inference. RESULTS: In applications to scRNA-seq data we demonstrate the potential of GPseudoRank to sample from complex and multi-modal posterior distributions and to identify phases of lower and higher pseudotime uncertainty during a biological process. GPseudoRank also correctly identifies cells precocious in their antiviral response and links uncertainty in the ordering to metastable states. A variant of the method extends the advantages of Bayesian modelling and MCMC to large droplet-based scRNA-seq datasets. AVAILABILITY AND IMPLEMENTATION: Our method is available on github: https://github.com/magStra/GPseudoRank. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
动机:许多伪时间方法为 scRNA-seq 数据提供了细胞排序的点估计。仍然有限数量的方法还对伪时间估计的不确定性进行建模。然而,仍然需要一种方法来从复杂和多峰的排序分布中进行采样,并估计在生物发育过程中排序不确定性的变化量,因为这可以支持选择适合基因聚类或网络推断的合适细胞。
结果:在对 scRNA-seq 数据的应用中,我们证明了 GPseudoRank 从复杂和多峰后验分布中进行采样的潜力,并能够识别生物过程中伪时间不确定性较低和较高的阶段。GPseudoRank 还能够正确识别抗病毒反应提前的细胞,并将排序中的不确定性与亚稳态联系起来。该方法的变体将贝叶斯建模和 MCMC 的优势扩展到基于大型液滴的 scRNA-seq 数据集。
可用性和实现:我们的方法可在 github 上获得:https://github.com/magStra/GPseudoRank。
补充信息:补充数据可在生物信息学在线获得。
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