NetSmooth: Network-smoothing based imputation for single cell RNA-seq.
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ABSTRACT:
SUBMITTER: Ronen J
PROVIDER: S-EPMC5814748 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Single-cell RNA sequencing is a powerful technology for obtaining transcriptomes at single-cell resolutions. However, it suffers from dropout events (i.e., excess zero counts) since only a small fraction of transcripts get sequenced in each cell during the sequencing process. This inherent sparsity of expression profiles hinders further characterizations at cell/gene-level such as cell type identification and downstream analysis. To alleviate this dropout issue we introduce a network-based method, netImpute, by leveraging the hidden information in gene co-expression networks to recover real signals. netImpute employs Random Walk with Restart (RWR) to adjust the gene expression level in a given cell by borrowing information from its neighbors in a gene co-expression network. Performance evaluation and comparison with existing tools on simulated data and seven real datasets show that netImpute substantially enhances clustering accuracy and data visualization clarity, thanks to its effective treatment of dropouts. While the idea of netImpute is general and can be applied with other types of networks such as cell co-expression network or protein-protein interaction (PPI) network, evaluation results show that gene co-expression network is consistently more beneficial, presumably because PPI network usually lacks cell type context, while cell co-expression network can cause information loss for rare cell types. Evaluation results on several biological datasets show that netImpute can more effectively recover missing transcripts in scRNA-seq data and enhance the identification and visualization of heterogeneous cell types than existing methods.
| S-EPMC7230610 | biostudies-literature
Project description:The emergence of single-cell RNA sequencing (scRNA-seq) technologies has enabled us to measure the expression levels of thousands of genes at single-cell resolution. However, insufficient quantities of starting RNA in the individual cells cause significant dropout events, introducing a large number of zero counts in the expression matrix. To circumvent this, we developed an autoencoder-based sparse gene expression matrix imputation method. AutoImpute, which learns the inherent distribution of the input scRNA-seq data and imputes the missing values accordingly with minimal modification to the biologically silent genes. When tested on real scRNA-seq datasets, AutoImpute performed competitively wrt., the existing single-cell imputation methods, on the grounds of expression recovery from subsampled data, cell-clustering accuracy, variance stabilization and cell-type separability.
| S-EPMC6218547 | biostudies-literature
Project description:Recent advances in single-cell RNA sequencing (scRNA-seq) technologies have yielded a powerful tool to measure gene expression of individual cells. One major challenge of the scRNA-seq data is that it usually contains a large amount of zero expression values, which often impairs the effectiveness of downstream analyses. Numerous data imputation methods have been proposed to deal with these "dropout" events, but this is a difficult task for such high-dimensional and sparse data. Furthermore, there have been debates on the nature of the sparsity, about whether the zeros are due to technological limitations or represent actual biology. To address these challenges, we propose Single-cell RNA-seq Correlation completion by ENsemble learning and Auxiliary information (SCENA), a novel approach that imputes the correlation matrix of the data of interest instead of the data itself. SCENA obtains a gene-by-gene correlation estimate by ensembling various individual estimates, some of which are based on known auxiliary information about gene expression networks. Our approach is a reliable method that makes no assumptions on the nature of sparsity in scRNA-seq data or the data distribution. By extensive simulation studies and real data applications, we demonstrate that SCENA is not only superior in gene correlation estimation, but also improves the accuracy and reliability of downstream analyses, including cell clustering, dimension reduction, and graphical model estimation to learn the gene expression network.
| S-EPMC9125575 | biostudies-literature
Project description:Motivation: Single-cell RNA sequencing has been proved to be revolutionary for its potential of zooming into complex biological systems. Genome-wide expression analysis at single-cell resolution provides a window into dynamics of cellular phenotypes. This facilitates the characterization of transcriptional heterogeneity in normal and diseased tissues under various conditions. It also sheds light on the development or emergence of specific cell populations and phenotypes. However, owing to the paucity of input RNA, a typical single cell RNA sequencing data features a high number of dropout events where transcripts fail to get amplified. Results: We introduce mcImpute, a low-rank matrix completion based technique to impute dropouts in single cell expression data. On a number of real datasets, application of mcImpute yields significant improvements in the separation of true zeros from dropouts, cell-clustering, differential expression analysis, cell type separability, the performance of dimensionality reduction techniques for cell visualization, and gene distribution. Availability and Implementation: https://github.com/aanchalMongia/McImpute_scRNAseq.
| S-EPMC6361810 | biostudies-literature
Project description:Single-cell RNA-seq data contain a large proportion of zeros for expressed genes. Such dropout events present a fundamental challenge for various types of data analyses. Here, we describe the SCRABBLE algorithm to address this problem. SCRABBLE leverages bulk data as a constraint and reduces unwanted bias towards expressed genes during imputation. Using both simulation and several types of experimental data, we demonstrate that SCRABBLE outperforms the existing methods in recovering dropout events, capturing true distribution of gene expression across cells, and preserving gene-gene relationship and cell-cell relationship in the data.
| S-EPMC6501316 | biostudies-literature
Project description:Single-cell RNA sequencing (scRNA-seq) facilitates the study of cell type heterogeneity and the construction of cell atlas. However, due to its limitations, many genes may be detected to have zero expressions, i.e. dropout events, leading to bias in downstream analyses and hindering the identification and characterization of cell types and cell functions. Although many imputation methods have been developed, their performances are generally lower than expected across different kinds and dimensions of data and application scenarios. Therefore, developing an accurate and robust single-cell gene expression data imputation method is still essential. Considering to maintain the original cell-cell and gene-gene correlations and leverage bulk RNA sequencing (bulk RNA-seq) data information, we propose scINRB, a single-cell gene expression imputation method with network regularization and bulk RNA-seq data. scINRB adopts network-regularized non-negative matrix factorization to ensure that the imputed data maintains the cell-cell and gene-gene similarities and also approaches the gene average expression calculated from bulk RNA-seq data. To evaluate the performance, we test scINRB on simulated and experimental datasets and compare it with other commonly used imputation methods. The results show that scINRB recovers gene expression accurately even in the case of high dropout rates and dimensions, preserves cell-cell and gene-gene similarities and improves various downstream analyses including visualization, clustering and trajectory inference.
| S-EPMC11006796 | biostudies-literature
Project description:A key challenge in analyzing single cell RNA-sequencing data is the large number of false zeros, where genes actually expressed in a given cell are incorrectly measured as unexpressed. We present a method based on low-rank matrix approximation which imputes these values while preserving biologically non-expressed genes (true biological zeros) at zero expression levels. We provide theoretical justification for this denoising approach and demonstrate its advantages relative to other methods on simulated and biological datasets.
| S-EPMC8752663 | biostudies-literature
Project description:Single-cell RNA-sequencing (scRNA-seq) enables the characterization of transcriptomic profiles at the single-cell resolution with increasingly high throughput. However, it suffers from many sources of technical noises, including insufficient mRNA molecules that lead to excess false zero values, termed dropouts. Computational approaches have been proposed to recover the biologically meaningful expression by borrowing information from similar cells in the observed dataset. However, these methods suffer from oversmoothing and removal of natural cell-to-cell stochasticity in gene expression. Here, we propose the generative adversarial networks (GANs) for scRNA-seq imputation (scIGANs), which uses generated cells rather than observed cells to avoid these limitations and balances the performance between major and rare cell populations. Evaluations based on a variety of simulated and real scRNA-seq datasets show that scIGANs is effective for dropout imputation and enhances various downstream analysis. ScIGANs is robust to small datasets that have very few genes with low expression and/or cell-to-cell variance. ScIGANs works equally well on datasets from different scRNA-seq protocols and is scalable to datasets with over 100 000 cells. We demonstrated in many ways with compelling evidence that scIGANs is not only an application of GANs in omics data but also represents a competing imputation method for the scRNA-seq data.
| S-EPMC7470961 | biostudies-literature
Project description:Single-cell RNA sequencing (scRNA-seq) methods are typically unable to quantify the expression levels of all genes in a cell, creating a need for the computational prediction of missing values ('dropout imputation'). Most existing dropout imputation methods are limited in the sense that they exclusively use the scRNA-seq dataset at hand and do not exploit external gene-gene relationship information. Further, it is unknown if all genes equally benefit from imputation or which imputation method works best for a given gene. Here, we show that a transcriptional regulatory network learned from external, independent gene expression data improves dropout imputation. Using a variety of human scRNA-seq datasets we demonstrate that our network-based approach outperforms published state-of-the-art methods. The network-based approach performs particularly well for lowly expressed genes, including cell-type-specific transcriptional regulators. Further, the cell-to-cell variation of 11.3% to 48.8% of the genes could not be adequately imputed by any of the methods that we tested. In those cases gene expression levels were best predicted by the mean expression across all cells, i.e. assuming no measurable expression variation between cells. These findings suggest that different imputation methods are optimal for different genes. We thus implemented an R-package called ADImpute (available via Bioconductor https://bioconductor.org/packages/release/bioc/html/ADImpute.html) that automatically determines the best imputation method for each gene in a dataset. Our work represents a paradigm shift by demonstrating that there is no single best imputation method. Instead, we propose that imputation should maximally exploit external information and be adapted to gene-specific features, such as expression level and expression variation across cells.
| S-EPMC8890719 | biostudies-literature
Project description:Motivation: The emergence of single-cell RNA sequencing (scRNA-seq) technology has paved the way for measuring RNA levels at single-cell resolution to study precise biological functions. However, the presence of a large number of missing values in its data will affect downstream analysis. This paper presents AdImpute: an imputation method based on semi-supervised autoencoders. The method uses another imputation method (DrImpute is used as an example) to fill the results as imputation weights of the autoencoder, and applies the cost function with imputation weights to learn the latent information in the data to achieve more accurate imputation. Results: As shown in clustering experiments with the simulated data sets and the real data sets, AdImpute is more accurate than other four publicly available scRNA-seq imputation methods, and minimally modifies the biologically silent genes. Overall, AdImpute is an accurate and robust imputation method.
| S-EPMC8456123 | biostudies-literature