scds: computational annotation of doublets in single-cell RNA sequencing data.

scds: computational annotation of doublets in single-cell RNA sequencing data.
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DOI:
10.1093/bioinformatics/btz698
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发表时间:
2020-02-15
期刊:
Bioinformatics (Oxford, England)
影响因子:
--
通讯作者:
Kostka D
Kostka D
中科院分区:
其他
文献类型:
--
作者:
Bais AS;Kostka D

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单细胞RNA测序(scRNA-seq)技术能够以单个细胞的分辨率研究转录异质性,并对生物医学研究产生越来越大的影响。然而,已知这些方法有时错误地将两个或更多个细胞视为单细胞,并且在这些实验的输出中存在许多所谓的双峰。在下游分析中将双联体作为单细胞处理可能会严重影响研究结论,因此需要用于识别双联体的计算策略。利用scds,我们提出了两种新的计算机双联体鉴定方法:基于共表达的双联体评分(cxds)和基于二元分类的双联体评分(bcds)。基于共表达的方法,cxds,利用二进制化(不存在/存在)的基因表达数据,并采用二项式模型的基因对的共表达,产生可解释的双重注释。另一方面,bcds使用二元分类方法从原始数据中区分人工双联体。我们将我们的方法和现有的计算双联体识别方法应用于四个具有实验双联体注释的数据集,并发现我们的方法至少与最先进的方法一样好,并且计算成本很小。我们观察到方法之间和数据集之间存在明显的差异,并且没有任何方法可以主导所有其他方法。总之,scds提供了一种可扩展的、有竞争力的方法,允许在几秒钟内对具有数千个细胞的数据集进行双重注释。 scds作为Bioconductor R包(doi:10.18129/B9.bioc.scds)实现。 补充数据可在Bioinformatics在线获得。
Single-cell RNA sequencing (scRNA-seq) technologies enable the study of transcriptional heterogeneity at the resolution of individual cells and have an increasing impact on biomedical research. However, it is known that these methods sometimes wrongly consider two or more cells as single cells, and that a number of so-called doublets is present in the output of such experiments. Treating doublets as single cells in downstream analyses can severely bias a study’s conclusions, and therefore computational strategies for the identification of doublets are needed. With scds, we propose two new approaches for in silico doublet identification: Co-expression based doublet scoring (cxds) and binary classification based doublet scoring (bcds). The co-expression based approach, cxds, utilizes binarized (absence/presence) gene expression data and, employing a binomial model for the co-expression of pairs of genes, yields interpretable doublet annotations. bcds, on the other hand, uses a binary classification approach to discriminate artificial doublets from original data. We apply our methods and existing computational doublet identification approaches to four datasets with experimental doublet annotations and find that our methods perform at least as well as the state of the art, at comparably little computational cost. We observe appreciable differences between methods and across datasets and that no approach dominates all others. In summary, scds presents a scalable, competitive approach that allows for doublet annotation of datasets with thousands of cells in a matter of seconds. scds is implemented as a Bioconductor R package (doi: 10.18129/B9.bioc.scds). Supplementary data are available at Bioinformatics online.
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