A systematic evaluation of single-cell RNA-sequencing imputation methods

Abstract Background The rapid development of single-cell RNA-sequencing (scRNA-seq) technologies has led to the emergence of many methods for removing systematic technical noises, including imputation methods, which aim to address the increased sparsity observed in single-cell data. Although many im...

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Main Authors: Wenpin Hou, Zhicheng Ji, Hongkai Ji, Stephanie C. Hicks
Format: Article
Language:English
Published: BMC 2020-08-01
Series:Genome Biology
Subjects:
Online Access:http://link.springer.com/article/10.1186/s13059-020-02132-x
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author Wenpin Hou
Zhicheng Ji
Hongkai Ji
Stephanie C. Hicks
author_facet Wenpin Hou
Zhicheng Ji
Hongkai Ji
Stephanie C. Hicks
author_sort Wenpin Hou
collection DOAJ
description Abstract Background The rapid development of single-cell RNA-sequencing (scRNA-seq) technologies has led to the emergence of many methods for removing systematic technical noises, including imputation methods, which aim to address the increased sparsity observed in single-cell data. Although many imputation methods have been developed, there is no consensus on how methods compare to each other. Results Here, we perform a systematic evaluation of 18 scRNA-seq imputation methods to assess their accuracy and usability. We benchmark these methods in terms of the similarity between imputed cell profiles and bulk samples and whether these methods recover relevant biological signals or introduce spurious noise in downstream differential expression, unsupervised clustering, and pseudotemporal trajectory analyses, as well as their computational run time, memory usage, and scalability. Methods are evaluated using data from both cell lines and tissues and from both plate- and droplet-based single-cell platforms. Conclusions We found that the majority of scRNA-seq imputation methods outperformed no imputation in recovering gene expression observed in bulk RNA-seq. However, the majority of the methods did not improve performance in downstream analyses compared to no imputation, in particular for clustering and trajectory analysis, and thus should be used with caution. In addition, we found substantial variability in the performance of the methods within each evaluation aspect. Overall, MAGIC, kNN-smoothing, and SAVER were found to outperform the other methods most consistently.
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spelling doaj.art-33348cd27b4b452ea163d6f1b74a1b052022-12-21T22:47:13ZengBMCGenome Biology1474-760X2020-08-0121113010.1186/s13059-020-02132-xA systematic evaluation of single-cell RNA-sequencing imputation methodsWenpin Hou0Zhicheng Ji1Hongkai Ji2Stephanie C. Hicks3Department of Biostatistics, Johns Hopkins Bloomberg School of Public HealthDepartment of Biostatistics, Johns Hopkins Bloomberg School of Public HealthDepartment of Biostatistics, Johns Hopkins Bloomberg School of Public HealthDepartment of Biostatistics, Johns Hopkins Bloomberg School of Public HealthAbstract Background The rapid development of single-cell RNA-sequencing (scRNA-seq) technologies has led to the emergence of many methods for removing systematic technical noises, including imputation methods, which aim to address the increased sparsity observed in single-cell data. Although many imputation methods have been developed, there is no consensus on how methods compare to each other. Results Here, we perform a systematic evaluation of 18 scRNA-seq imputation methods to assess their accuracy and usability. We benchmark these methods in terms of the similarity between imputed cell profiles and bulk samples and whether these methods recover relevant biological signals or introduce spurious noise in downstream differential expression, unsupervised clustering, and pseudotemporal trajectory analyses, as well as their computational run time, memory usage, and scalability. Methods are evaluated using data from both cell lines and tissues and from both plate- and droplet-based single-cell platforms. Conclusions We found that the majority of scRNA-seq imputation methods outperformed no imputation in recovering gene expression observed in bulk RNA-seq. However, the majority of the methods did not improve performance in downstream analyses compared to no imputation, in particular for clustering and trajectory analysis, and thus should be used with caution. In addition, we found substantial variability in the performance of the methods within each evaluation aspect. Overall, MAGIC, kNN-smoothing, and SAVER were found to outperform the other methods most consistently.http://link.springer.com/article/10.1186/s13059-020-02132-xGene expressionSingle-cell RNA-sequencingImputationBenchmark
spellingShingle Wenpin Hou
Zhicheng Ji
Hongkai Ji
Stephanie C. Hicks
A systematic evaluation of single-cell RNA-sequencing imputation methods
Genome Biology
Gene expression
Single-cell RNA-sequencing
Imputation
Benchmark
title A systematic evaluation of single-cell RNA-sequencing imputation methods
title_full A systematic evaluation of single-cell RNA-sequencing imputation methods
title_fullStr A systematic evaluation of single-cell RNA-sequencing imputation methods
title_full_unstemmed A systematic evaluation of single-cell RNA-sequencing imputation methods
title_short A systematic evaluation of single-cell RNA-sequencing imputation methods
title_sort systematic evaluation of single cell rna sequencing imputation methods
topic Gene expression
Single-cell RNA-sequencing
Imputation
Benchmark
url http://link.springer.com/article/10.1186/s13059-020-02132-x
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