Robust integration of multiple single-cell RNA sequencing datasets using a single reference space.

Robust integration of multiple single-cell RNA sequencing datasets using a single reference space.
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DOI:
10.1038/s41587-021-00859-x
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发表时间:
2021-07
影响因子:
46.9
通讯作者:
Zheng D
Zheng D
中科院分区:
工程技术1区
文献类型:
--
作者:
Liu Y;Wang T;Zhou B;Zheng D

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在单细胞RNA测序(scRNA-seq)的许多生物应用中,需要对多个批次或研究的数据进行综合分析。目前的方法通常使用共享的细胞类型或数据集之间的协方差相关性来实现整合,这可能会使生物信号失真。在这里,我们介绍了一种算法,使用基因特征向量从参考数据集建立一个全球框架的整合。使用模拟和真实的数据集,我们证明了这种方法,称为参考主成分整合(RPCI),始终优于其他方法的多个指标,具有明显的优势,在保留真正的跨样本基因表达差异匹配细胞类型,如那些存在于细胞在不同的发育阶段或扰动与对照研究。此外,RPCI在集成多个数据集时保持这种强大的性能。最后,我们将RPCI应用于小鼠肠道内胚层发育的scRNA-seq数据,并揭示了帮助建立内脏内胚层前后轴的遗传程序的时间出现。
In many biological applications of single-cell RNA sequencing (scRNA-seq), an integrated analysis of data from multiple batches or studies is necessary. Current methods typically achieve integration using shared cell types or covariance correlation between datasets, which can distort biological signals. Here we introduce an algorithm that uses the gene eigenvectors from a reference dataset to establish a global frame for integration. Using simulated and real datasets, we demonstrate that this approach, called Reference Principal Component Integration (RPCI), consistently outperforms other methods by multiple metrics, with clear advantages in preserving genuine cross-sample gene expression differences in matching cell types, such as those present in cells at distinct developmental stages or in perturbated versus control studies. Moreover, RPCI maintains this robust performance when multiple datasets are integrated. Finally, we applied RPCI to scRNA-seq data for mouse gut endoderm development and revealed temporal emergence of genetic programs helping establish the anterior-posterior axis in visceral endoderm.
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