GPseudoClust: deconvolution of shared pseudo-profiles at single-cell resolution.

GPseudoClust: deconvolution of shared pseudo-profiles at single-cell resolution.
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DOI:
10.1093/bioinformatics/btz778
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发表时间:
2020-03-01
期刊:
Bioinformatics (Oxford, England)
影响因子:
--
通讯作者:
Wernisch L
Wernisch L
中科院分区:
其他
文献类型:
--
作者:
Strauss ME;Kirk PDW;Reid JE;Wernisch L

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已经开发了许多方法,通过使用大量rna测序或微阵列数据,根据mRNA表达随时间的变化对基因进行聚类。然而,单细胞数据可能会对这些算法提出一个特别的挑战,因为细胞的时间顺序不能直接观察到。解决这个问题的一种方法是首先使用伪时间方法对单元排序,然后对时间过程数据应用聚类技术。然而,伪时间估计受到高度不确定性的影响,未能考虑到这种不确定性很容易导致错误和/或过度自信的基因簇。提出的GPseudoClust方法是一种联合推断伪时间顺序和基因簇的新方法,并量化了两者的不确定性。GPseudoClust结合了最新的伪时间推断方法与非参数贝叶斯聚类方法,高效的马尔可夫链蒙特卡罗采样和新的辅助计算的子采样策略。我们考虑了广泛的模拟和实验数据集,以证明GPseudoClust在一系列设置中的有效性。实现可在GitHub: https://github.com/magStra/nonparametricSummaryPSM和https://github.com/magStra/GPseudoClust。补充数据可在生物信息学网站获得。
Many methods have been developed to cluster genes on the basis of their changes in mRNA expression over time, using bulk RNA-seq or microarray data. However, single-cell data may present a particular challenge for these algorithms, since the temporal ordering of cells is not directly observed. One way to address this is to first use pseudotime methods to order the cells, and then apply clustering techniques for time course data. However, pseudotime estimates are subject to high levels of uncertainty, and failing to account for this uncertainty is liable to lead to erroneous and/or over-confident gene clusters. The proposed method, GPseudoClust, is a novel approach that jointly infers pseudotemporal ordering and gene clusters, and quantifies the uncertainty in both. GPseudoClust combines a recent method for pseudotime inference with non-parametric Bayesian clustering methods, efficient Markov Chain Monte Carlo sampling and novel subsampling strategies which aid computation. We consider a broad array of simulated and experimental datasets to demonstrate the effectiveness of GPseudoClust in a range of settings. An implementation is available on GitHub: https://github.com/magStra/nonparametricSummaryPSM and https://github.com/magStra/GPseudoClust. Supplementary data are available at Bioinformatics online.
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