逆向学习实现了单细胞 RNA 数据的无偏全生物体跨物种配准

Samuel Cooper, Juan Javier Diaz-Mejia, Brendan Innes, Elias Williams, Dylan Mendonca, Octavian Focsa, Allison Nixon, Swechha Singh, Ronen Schuster, Boris Hinz, Matthew Buechler
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引用次数: 0

摘要

当今的单细胞 RNA(scRNA)数据集仍然各自为政,这是因为大规模整合这些数据集面临巨大挑战。此外,大多数大规模运行的 scRNA 分析工具利用的是监督技术,而监督技术不足以进行细胞类型鉴定和发现。在这里,我们证明了使用无监督模型对scRNA数据进行配准在生物体范围内和物种之间都是准确的。为此,我们展示了如何利用我们称之为批量对抗性单细胞变异推理(BA-scVI)的深度学习模型的对抗性训练来对齐标准化的基准数据集,这些数据集由数十个 scRNA 研究组成,横跨人类和小鼠的组织。对所学细胞类型空间的分析使我们能够确定进化上保守的细胞类型,包括未得到充分重视的补体表达巨噬细胞和成纤维细胞类型,从而为细胞类型进化的大型系统发育分析铺平道路。最后,我们通过一个在线界面提供了对 scREF、scREF-mu 和 BA-scVI 模型的广泛访问,以便进行图谱探索和新数据的拖放比对。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Adversarial learning enables unbiased organism-wide cross-species alignment of single-cell RNA data
Today's single-cell RNA (scRNA) datasets remain siloed, due to significant challenges associated with their integration at scale. Moreover, most scRNA analysis tools that operate at scale leverage supervised techniques that are insufficient for cell-type identification and discovery. Here we demonstrate that alignment of scRNA data using unsupervised models is accurate at both an organism wide scale and between species. To do this we show how adversarial training of a deep-learning model we term batch-adversarial single-cell variational inference (BA-scVI) can be employed to align standardized benchmark datasets that comprise dozens of scRNA studies and span tissues in both humans and mice. Analysis of the learnt cell-type space then enables us to identify evolutionarily conserved cell-types, including underappreciated complement expressing macrophage and fibroblast types, paving the way to larger phylogenetic analysis of cell-type evolution. Finally, we provide broad access to scREF, scREF-mu and the BA-scVI model via an online interface for atlas exploration and drag-and-drop alignment of new data.
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