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Selecting gene features for unsupervised analysis of single-cell gene expression data.

ABSTRACT: Single-cell RNA sequencing (scRNA-seq) technologies facilitate the characterization of transcriptomic landscapes in diverse species, tissues, and cell types with unprecedented molecular resolution. In order to evaluate various biological hypotheses using high-dimensional single-cell gene expression data, most computational and statistical methods depend on a gene feature selection step to identify genes with high biological variability and reduce computational complexity. Even though many gene selection methods have been developed for scRNA-seq analysis, there lacks a systematic comparison of the assumptions, statistical models, and selection criteria used by these methods. In this article, we summarize and discuss 17 computational methods for selecting gene features in unsupervised analysis of single-cell gene expression data, with unified notations and statistical frameworks. Our discussion provides a useful summary to help practitioners select appropriate methods based on their assumptions and applicability, and to assist method developers in designing new computational tools for unsupervised learning of scRNA-seq data.

SUBMITTER: Sheng J

PROVIDER: S-EPMC8574996 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Selecting gene features for unsupervised analysis of single-cell gene expression data.

Sheng Jie J Li Wei Vivian WV

Briefings in bioinformatics 20211101 6

Single-cell RNA sequencing (scRNA-seq) technologies facilitate the characterization of transcriptomic landscapes in diverse species, tissues, and cell types with unprecedented molecular resolution. In order to evaluate various biological hypotheses using high-dimensional single-cell gene expression data, most computational and statistical methods depend on a gene feature selection step to identify genes with high biological variability and reduce computational complexity. Even though many gene s ...[more]

PMID: 34351383

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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

Selecting gene features for unsupervised analysis of single-cell gene expression data.

Publications

Selecting gene features for unsupervised analysis of single-cell gene expression data.

Similar Datasets

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