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Fast identification of differential distributions in single-cell RNA-sequencing data with waddR.

ABSTRACT: Single-cell gene expression distributions measured by single-cell RNA-sequencing (scRNA-seq) often display complex differences between samples. These differences are biologically meaningful but cannot be identified using standard methods for differential expression. Here, we derive and implement a flexible and fast differential distribution testing procedure based on the 2-Wasserstein distance. Our method is able to detect any type of difference in distribution between conditions. To interpret distributional differences, we decompose the 2-Wasserstein distance into terms that capture the relative contribution of changes in mean, variance and shape to the overall difference. Finally, we derive mathematical generalisations that allow our method to be used in a broad range of disciplines other than scRNA-seq or bioinformatics. Our methods are implemented in the R/Bioconductor package waddR, which is freely available at https://github.com/goncalves-lab/waddR, along with documentation and examples. Supplementary data are available at Bioinformatics online.

SUBMITTER: Schefzik R

PROVIDER: S-EPMC8504634 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Fast identification of differential distributions in single-cell RNA-sequencing data with waddR.

Schefzik Roman R Flesch Julian J Goncalves Angela A

Bioinformatics (Oxford, England) 20211001 19

<h4>Motivation</h4>Single-cell gene expression distributions measured by single-cell RNA-sequencing (scRNA-seq) often display complex differences between samples. These differences are biologically meaningful but cannot be identified using standard methods for differential expression.<h4>Results</h4>Here, we derive and implement a flexible and fast differential distribution testing procedure based on the 2-Wasserstein distance. Our method is able to detect any type of difference in distribution ...[more]

PMID: 33792651

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Project description:BackgroundThe analysis of single-cell RNA sequencing (scRNAseq) data plays an important role in understanding the intrinsic and extrinsic cellular processes in biological and biomedical research. One significant effort in this area is the detection of differentially expressed (DE) genes. scRNAseq data, however, are highly heterogeneous and have a large number of zero counts, which introduces challenges in detecting DE genes. Addressing these challenges requires employing new approaches beyond the conventional ones, which are based on a nonzero difference in average expression. Several methods have been developed for differential gene expression analysis of scRNAseq data. To provide guidance on choosing an appropriate tool or developing a new one, it is necessary to evaluate and compare the performance of differential gene expression analysis methods for scRNAseq data.ResultsIn this study, we conducted a comprehensive evaluation of the performance of eleven differential gene expression analysis software tools, which are designed for scRNAseq data or can be applied to them. We used simulated and real data to evaluate the accuracy and precision of detection. Using simulated data, we investigated the effect of sample size on the detection accuracy of the tools. Using real data, we examined the agreement among the tools in identifying DE genes, the run time of the tools, and the biological relevance of the detected DE genes.ConclusionsIn general, agreement among the tools in calling DE genes is not high. There is a trade-off between true-positive rates and the precision of calling DE genes. Methods with higher true positive rates tend to show low precision due to their introducing false positives, whereas methods with high precision show low true positive rates due to identifying few DE genes. We observed that current methods designed for scRNAseq data do not tend to show better performance compared to methods designed for bulk RNAseq data. Data multimodality and abundance of zero read counts are the main characteristics of scRNAseq data, which play important roles in the performance of differential gene expression analysis methods and need to be considered in terms of the development of new methods.

Dataset Information

Fast identification of differential distributions in single-cell RNA-sequencing data with waddR.

Publications

Fast identification of differential distributions in single-cell RNA-sequencing data with waddR.

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