scholarly journals McImpute: Matrix completion based imputation for single cell RNA-seq data

2018 ◽  
Author(s):  
Aanchal Mongia ◽  
Debarka Sengupta ◽  
Angshul Majumdar

AbstractMotivationSingle 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 characterization of transcriptional heterogeneity in normal and diseased tissues under various conditions. It also sheds light on 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.ResultsWe 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 separation of true zeros from dropouts, cell-clustering, differential expression analysis, cell type separability, performance of dimensionality reduction techniques for cell visualization and gene distribution.Availability and Implementationhttps://github.com/aanchalMongia/McImpute_scRNAseq

2021 ◽  
Author(s):  
Meichen Dong ◽  
Yiping He ◽  
Yuchao Jiang ◽  
Fei Zou

In contrast to differential gene expression analysis at single-gene level, gene regulatory networks (GRN) analysis depicts complex transcriptomic interactions among genes for better understandings of underlying genetic architectures of human diseases and traits. Recently, single-cell RNA sequencing (scRNA-seq) data has started to be used for constructing GRNs at a much finer resolution than bulk RNA-seq data and microarray data. However, scRNA-seq data are inherently sparse which hinders the direct application of the popular Gaussian graphical models (GGMs). Furthermore, most existing approaches for constructing GRNs with scRNA-seq data only consider gene networks under one condition. To better understand GRNs under different but related conditions with single-cell resolution, we propose to construct Joint Gene Networks with scRNA-seq data (JGNsc) using the GGMs framework. To facilitate the use of GGMs, JGNsc first proposes a hybrid imputation procedure that combines a Bayesian zero-inflated Poisson (ZIP) model with an iterative low-rank matrix completion step to efficiently impute zero-inflated counts resulted from technical artifacts. JGNsc then transforms the imputed data via a nonparanormal transformation, based on which joint GGMs are constructed. We demonstrate JGNsc and assess its performance using synthetic data. The application of JGNsc on two cancer clinical studies of medulloblastoma and glioblastoma identifies novel findings in addition to confirming well-known biological results.


Author(s):  
Yinlei Hu ◽  
Bin Li ◽  
Falai Chen ◽  
Kun Qu

Abstract Unsupervised clustering is a fundamental step of single-cell RNA sequencing data analysis. This issue has inspired several clustering methods to classify cells in single-cell RNA sequencing data. However, accurate prediction of the cell clusters remains a substantial challenge. In this study, we propose a new algorithm for single-cell RNA sequencing data clustering based on Sparse Optimization and low-rank matrix factorization (scSO). We applied our scSO algorithm to analyze multiple benchmark datasets and showed that the cluster number predicted by scSO was close to the number of reference cell types and that most cells were correctly classified. Our scSO algorithm is available at https://github.com/QuKunLab/scSO. Overall, this study demonstrates a potent cell clustering approach that can help researchers distinguish cell types in single-cell RNA sequencing data.


2018 ◽  
Vol 19 (1) ◽  
Author(s):  
Wenan Chen ◽  
Yan Li ◽  
John Easton ◽  
David Finkelstein ◽  
Gang Wu ◽  
...  

2018 ◽  
Author(s):  
Wenhao Tang ◽  
François Bertaux ◽  
Philipp Thomas ◽  
Claire Stefanelli ◽  
Malika Saint ◽  
...  

Normalisation of single cell RNA sequencing (scRNA-seq) data is a prerequisite to their interpretation. The marked technical variability and high amounts of missing observations typical of scRNA-seq datasets make this task particularly challenging. Here, we introduce bayNorm, a novel Bayesian approach for scaling and inference of scRNA-seq counts. The method’s likelihood function follows a binomial model of mRNA capture, while priors are estimated from expression values across cells using an empirical Bayes approach. We demonstrate using publicly-available scRNA-seq datasets and simulated expression data that bayNorm allows robust imputation of missing values generating realistic transcript distributions that match single molecule FISH measurements. Moreover, by using priors informed by dataset structures, bayNorm improves accuracy and sensitivity of differential expression analysis and reduces batch effect compared to other existing methods. Altogether, bayNorm provides an efficient, integrated solution for global scaling normalisation, imputation and true count recovery of gene expression measurements from scRNA-seq data.


2019 ◽  
Author(s):  
Haruka Ozaki ◽  
Tetsutaro Hayashi ◽  
Mana Umeda ◽  
Itoshi Nikaido

AbstractBackgroundRead coverage of RNA sequencing data reflects gene expression and RNA processing events. Single-cell RNA sequencing (scRNA-seq) methods, particularly “full-length” ones, provide read coverage of many individual cells and have the potential to reveal cellular heterogeneity in RNA transcription and processing. However, visualization tools suited to highlighting cell-to-cell heterogeneity in read coverage are still lacking.ResultsHere, we have developed Millefy, a tool for visualizing read coverage of scRNA-seq data in genomic contexts. Millefy is designed to show read coverage of all individual cells at once in genomic contexts and to highlight cell-to-cell heterogeneity in read coverage. By visualizing read coverage of all cells as a heat map and dynamically reordering cells based on diffusion maps, Millefy facilitates discovery of “local” region-specific, cell-to-cell heterogeneity in read coverage, including variability of transcribed regions.ConclusionsMillefy simplifies the examination of cellular heterogeneity in RNA transcription and processing events using scRNA-seq data. Millefy is available as an R package (https://github.com/yuifu/millefy) and a Docker image to help use Millefy on the Jupyter notebook (https://hub.docker.com/r/yuifu/datascience-notebook-millefy).


2021 ◽  
Author(s):  
Gerard A. Bouland ◽  
Ahmed Mahfouz ◽  
Marcel J.T. Reinders

AbstractSingle-cell RNA sequencing data is characterized by a large number of zero counts, yet there is growing evidence that these zeros reflect biological rather than technical artifacts. We propose differential dropout analysis (DDA), as an alternative to differential expression analysis (DEA), to identify the effects of biological variation in single-cell RNA sequencing data. Using 16 publicly available datasets, we show that dropout patterns are biological in nature and can assess the relative abundance of transcripts more robustly than counts.


2020 ◽  
Vol 16 (5) ◽  
pp. 465-473
Author(s):  
Ye-Sen Sun ◽  
Le Ou-Yang ◽  
Dao-Qing Dai

The development of single-cell RNA-sequencing (scRNA-seq) technologies brings tremendous opportunities for quantitative research and analyses at the cellular level.


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