scholarly journals ILoReg: a tool for high-resolution cell population identification from single-cell RNA-seq data

2020 ◽  
Author(s):  
Johannes Smolander ◽  
Sini Junttila ◽  
Mikko S Venäläinen ◽  
Laura L Elo
Keyword(s):  
Feature Extraction ◽  
High Resolution ◽  
Single Cell ◽  
Cell Population ◽  
Learning Algorithm ◽  
R Package ◽  
Supplementary Information ◽  
Cell Populations ◽  
Rna Seq ◽  
Pancreatic Cell

Abstract Motivation Single-cell RNA-seq allows researchers to identify cell populations based on unsupervised clustering of the transcriptome. However, subpopulations can have only subtle transcriptomic differences and the high dimensionality of the data makes their identification challenging. Results We introduce ILoReg, an R package implementing a new cell population identification method that improves identification of cell populations with subtle differences through a probabilistic feature extraction step that is applied before clustering and visualization. The feature extraction is performed using a novel machine learning algorithm, called iterative clustering projection (ICP), that uses logistic regression and clustering similarity comparison to iteratively cluster data. Remarkably, ICP also manages to integrate feature selection with the clustering through L1-regularization, enabling the identification of genes that are differentially expressed between cell populations. By combining solutions of multiple ICP runs into a single consensus solution, ILoReg creates a representation that enables investigating cell populations with a high resolution. In particular, we show that the visualization of ILoReg allows segregation of immune and pancreatic cell populations in a more pronounced manner compared with current state-of-the-art methods. Availability and implementation ILoReg is available as an R package at https://bioconductor.org/packages/ILoReg. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals ILoReg enables high-resolution cell population identification from single-cell RNA-seq data

2020 ◽  
Author(s):  
Johannes Smolander ◽  
Sini Junttila ◽  
Mikko S Venäläinen ◽  
Laura L Elo
Keyword(s):  
Feature Extraction ◽  
High Resolution ◽  
Single Cell ◽  
Cell Population ◽  
R Package ◽  
High Dimensionality ◽  
Cell Populations ◽  
Rna Seq ◽  
Extraction Step ◽  
Resolution Cell

AbstractSingle-cell RNA-seq allows researchers to identify cell populations based on unsupervised clustering of the transcriptome. However, subpopulations can have only subtle transcriptomic differences and the high dimensionality of the data makes their identification challenging. We introduce ILoReg (https://github.com/elolab/iloreg), an R package implementing a new cell population identification method that achieves high differentiation resolution through a probabilistic feature extraction step that is applied before clustering and visualization.

ExperimentSubset: an R package to manage subsets of Bioconductor Experiment objects

2021 ◽  
Author(s):  
Irzam Sarfraz ◽  
Muhammad Asif ◽  
Joshua D Campbell
Keyword(s):  
Single Cell ◽  
R Package ◽  
Poor Quality ◽  
Data Matrix ◽  
Supplementary Information ◽  
Data Provenance ◽  
Rna Seq ◽  
Efficient Management ◽  
The Matrix ◽  
The Relationship

Abstract Motivation R Experiment objects such as the SummarizedExperiment or SingleCellExperiment are data containers for storing one or more matrix-like assays along with associated row and column data. These objects have been used to facilitate the storage and analysis of high-throughput genomic data generated from technologies such as single-cell RNA sequencing. One common computational task in many genomics analysis workflows is to perform subsetting of the data matrix before applying down-stream analytical methods. For example, one may need to subset the columns of the assay matrix to exclude poor-quality samples or subset the rows of the matrix to select the most variable features. Traditionally, a second object is created that contains the desired subset of assay from the original object. However, this approach is inefficient as it requires the creation of an additional object containing a copy of the original assay and leads to challenges with data provenance. Results To overcome these challenges, we developed an R package called ExperimentSubset, which is a data container that implements classes for efficient storage and streamlined retrieval of assays that have been subsetted by rows and/or columns. These classes are able to inherently provide data provenance by maintaining the relationship between the subsetted and parent assays. We demonstrate the utility of this package on a single-cell RNA-seq dataset by storing and retrieving subsets at different stages of the analysis while maintaining a lower memory footprint. Overall, the ExperimentSubset is a flexible container for the efficient management of subsets. Availability and implementation ExperimentSubset package is available at Bioconductor: https://bioconductor.org/packages/ExperimentSubset/ and Github: https://github.com/campbio/ExperimentSubset. Supplementary information Supplementary data are available at Bioinformatics online.

SMILE: Mutual Information Learning for Integration of Single-cell Omics Data

2021 ◽  
Author(s):  
Yang Xu ◽  
Priyojit Das ◽  
Rachel Patton McCord
Keyword(s):  
Deep Learning ◽  
Mutual Information ◽  
Single Cell ◽  
Learning Algorithm ◽  
Cellular Systems ◽  
Supplementary Information ◽  
Omics Data ◽  
Learning Approaches ◽  
Rna Seq ◽  
Integrate Data

Abstract Motivation Deep learning approaches have empowered single-cell omics data analysis in many ways and generated new insights from complex cellular systems. As there is an increasing need for single cell omics data to be integrated across sources, types, and features of data, the challenges of integrating single-cell omics data are rising. Here, we present an unsupervised deep learning algorithm that learns discriminative representations for single-cell data via maximizing mutual information, SMILE (Single-cell Mutual Information Learning). Results Using a unique cell-pairing design, SMILE successfully integrates multi-source single-cell transcriptome data, removing batch effects and projecting similar cell types, even from different tissues, into the shared space. SMILE can also integrate data from two or more modalities, such as joint profiling technologies using single-cell ATAC-seq, RNA-seq, DNA methylation, Hi-C, and ChIP data. When paired cells are known, SMILE can integrate data with unmatched feature, such as genes for RNA-seq and genome wide peaks for ATAC-seq. Integrated representations learned from joint profiling technologies can then be used as a framework for comparing independent single source data. Supplementary information Supplementary data are available at Bioinformatics online. The source code of SMILE including analyses of key results in the study can be found at: https://github.com/rpmccordlab/SMILE.

scholarly journals DEsingle for detecting three types of differential expression in single-cell RNA-seq data

2017 ◽  
Author(s):  
Zhun Miao ◽  
Ke Deng ◽  
Xiaowo Wang ◽  
Xuegong Zhang
Keyword(s):  
Single Cell ◽  
Differential Expression ◽  
Negative Binomial ◽  
Single Cells ◽  
R Package ◽  
Supplementary Information ◽  
Binomial Model ◽  
Supplementary Data ◽  
Rna Seq ◽  
Real Zeros

AbstractSummaryThe excessive amount of zeros in single-cell RNA-seq data include “real” zeros due to the on-off nature of gene transcription in single cells and “dropout” zeros due to technical reasons. Existing differential expression (DE) analysis methods cannot distinguish these two types of zeros. We developed an R package DEsingle which employed Zero-Inflated Negative Binomial model to estimate the proportion of real and dropout zeros and to define and detect 3 types of DE genes in single-cell RNA-seq data with higher accuracy.Availability and ImplementationThe R package DEsingle is freely available at https://github.com/miaozhun/DEsingle and is under Bioconductor’s consideration [email protected] informationSupplementary data are available at bioRxiv online.

scholarly journals DECENT: differential expression with capture efficiency adjustmeNT for single-cell RNA-seq data

2019 ◽  
Vol 35 (24) ◽  
pp. 5155-5162 ◽  
Author(s):  
Chengzhong Ye ◽  
Terence P Speed ◽  
Agus Salim
Keyword(s):  
Single Cell ◽  
Differential Expression ◽  
Type I Error ◽  
R Package ◽  
Supplementary Information ◽  
Type I ◽  
Common Phenomenon ◽  
Rna Seq ◽  
Capture Process ◽  
Technological Platforms

Abstract Motivation Dropout is a common phenomenon in single-cell RNA-seq (scRNA-seq) data, and when left unaddressed it affects the validity of the statistical analyses. Despite this, few current methods for differential expression (DE) analysis of scRNA-seq data explicitly model the process that gives rise to the dropout events. We develop DECENT, a method for DE analysis of scRNA-seq data that explicitly and accurately models the molecule capture process in scRNA-seq experiments. Results We show that DECENT demonstrates improved DE performance over existing DE methods that do not explicitly model dropout. This improvement is consistently observed across several public scRNA-seq datasets generated using different technological platforms. The gain in improvement is especially large when the capture process is overdispersed. DECENT maintains type I error well while achieving better sensitivity. Its performance without spike-ins is almost as good as when spike-ins are used to calibrate the capture model. Availability and implementation The method is implemented as a publicly available R package available from https://github.com/cz-ye/DECENT. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals scRNABatchQC: multi-samples quality control for single cell RNA-seq data

2019 ◽  
Vol 35 (24) ◽  
pp. 5306-5308
Author(s):  
Qi Liu ◽  
Quanhu Sheng ◽  
Jie Ping ◽  
Marisol Adelina Ramirez ◽  
Ken S Lau ◽  
...  
Keyword(s):  
Single Cell ◽  
R Package ◽  
Supplementary Information ◽  
Rna Seq ◽  
Technical Artifact ◽  
Multiple Sample ◽  
Systematic Biases ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome ◽  
Spurious Results

Abstract Summary Single cell RNA sequencing is a revolutionary technique to characterize inter-cellular transcriptomics heterogeneity. However, the data are noise-prone because gene expression is often driven by both technical artifacts and genuine biological variations. Proper disentanglement of these two effects is critical to prevent spurious results. While several tools exist to detect and remove low-quality cells in one single cell RNA-seq dataset, there is lack of approach to examining consistency between sample sets and detecting systematic biases, batch effects and outliers. We present scRNABatchQC, an R package to compare multiple sample sets simultaneously over numerous technical and biological features, which gives valuable hints to distinguish technical artifact from biological variations. scRNABatchQC helps identify and systematically characterize sources of variability in single cell transcriptome data. The examination of consistency across datasets allows visual detection of biases and outliers. Availability and implementation scRNABatchQC is freely available at https://github.com/liuqivandy/scRNABatchQC as an R package. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals scBatch: batch-effect correction of RNA-seq data through sample distance matrix adjustment

2020 ◽  
Vol 36 (10) ◽  
pp. 3115-3123 ◽  
Author(s):  
Teng Fei ◽  
Tianwei Yu
Keyword(s):  
Single Cell ◽  
Differential Expression Analysis ◽  
Distance Matrix ◽  
Real Data ◽  
R Package ◽  
Batch Effect ◽  
Supplementary Information ◽  
Rna Seq ◽  
Sequencing Data ◽  
Gene Differential Expression

Abstract Motivation Batch effect is a frequent challenge in deep sequencing data analysis that can lead to misleading conclusions. Existing methods do not correct batch effects satisfactorily, especially with single-cell RNA sequencing (RNA-seq) data. Results We present scBatch, a numerical algorithm for batch-effect correction on bulk and single-cell RNA-seq data with emphasis on improving both clustering and gene differential expression analysis. scBatch is not restricted by assumptions on the mechanism of batch-effect generation. As shown in simulations and real data analyses, scBatch outperforms benchmark batch-effect correction methods. Availability and implementation The R package is available at github.com/tengfei-emory/scBatch. The code to generate results and figures in this article is available at github.com/tengfei-emory/scBatch-paper-scripts. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals SPARSim single cell: a count data simulator for scRNA-seq data

2019 ◽  
Author(s):  
Giacomo Baruzzo ◽  
Ilaria Patuzzi ◽  
Barbara Di Camillo
Keyword(s):  
Single Cell ◽  
Count Data ◽  
Simulated Data ◽  
Real Data ◽  
R Package ◽  
Supplementary Information ◽  
Rna Seq ◽  
Distribution Of Zeros ◽  
New Methods ◽  
Research Fields

Abstract Motivation Single cell RNA-seq (scRNA-seq) count data show many differences compared with bulk RNA-seq count data, making the application of many RNA-seq pre-processing/analysis methods not straightforward or even inappropriate. For this reason, the development of new methods for handling scRNA-seq count data is currently one of the most active research fields in bioinformatics. To help the development of such new methods, the availability of simulated data could play a pivotal role. However, only few scRNA-seq count data simulators are available, often showing poor or not demonstrated similarity with real data. Results In this article we present SPARSim, a scRNA-seq count data simulator based on a Gamma-Multivariate Hypergeometric model. We demonstrate that SPARSim allows to generate count data that resemble real data in terms of count intensity, variability and sparsity, performing comparably or better than one of the most used scRNA-seq simulator, Splat. In particular, SPARSim simulated count matrices well resemble the distribution of zeros across different expression intensities observed in real count data. Availability and implementation SPARSim R package is freely available at http://sysbiobig.dei.unipd.it/? q=SPARSim and at https://gitlab.com/sysbiobig/sparsim. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals scCancer: a package for automated processing of single cell RNA-seq data in cancer

2019 ◽  
Author(s):  
Wenbo Guo ◽  
Dongfang Wang ◽  
Shicheng Wang ◽  
Yiran Shan ◽  
Jin Gu
Keyword(s):  
Single Cell ◽  
Learning Algorithm ◽  
R Package ◽  
Rna Seq ◽  
Cell Level ◽  
Quality Control Metrics ◽  
Automated Processing ◽  
Cellular Phenotypes ◽  
User Friendly ◽  
Processing Steps

AbstractSummaryMolecular heterogeneities bring great challenges for cancer diagnosis and treatment. Recent advance in single cell RNA-sequencing (scRNA-seq) technology make it possible to study cancer transcriptomic heterogeneities at single cell level. Here, we develop an R package named scCancer which focuses on processing and analyzing scRNA-seq data for cancer research. Except basic data processing steps, this package takes several special considerations for cancer-specific features. Firstly, the package introduced comprehensive quality control metrics. Secondly, it used a data-driven machine learning algorithm to accurately identify major cancer microenvironment cell populations. Thirdly, it estimated a malignancy score to classify malignant (cancerous) and non-malignant cells. Then, it analyzed intra-tumor heterogeneities by key cellular phenotypes (such as cell cycle and stemness) and gene signatures. Finally, a user-friendly graphic report was generated for all the analyses.Availabilityhttp://lifeome.net/software/sccancer/[email protected]

scholarly journals SIMLR: a tool for large-scale single-cell analysis by multi-kernel learning

2017 ◽  
Author(s):  
Bo Wang ◽  
Daniele Ramazzotti ◽  
Luca De Sano ◽  
Junjie Zhu ◽  
Emma Pierson ◽  
...  
Keyword(s):  
Single Cell ◽  
Large Scale ◽  
Single Cell Analysis ◽  
R Package ◽  
Supplementary Information ◽  
Cell Analysis ◽  
Rna Seq ◽  
A Cell ◽  
Supplementary Material ◽  
Public Datasets

AbstractMotivationWe here present SIMLR (Single-cell Interpretation via Multi-kernel LeaRning), an open-source tool that implements a novel framework to learn a cell-to-cell similarity measure from single-cell RNA-seq data. SIMLR can be effectively used to perform tasks such as dimension reduction, clustering, and visualization of heterogeneous populations of cells. SIMLR was benchmarked against state-of-the-art methods for these three tasks on several public datasets, showing it to be scalable and capable of greatly improving clustering performance, as well as providing valuable insights by making the data more interpretable via better a visualization.Availability and ImplementationSIMLR is available on GitHub in both R and MATLAB implementations. Furthermore, it is also available as an R package on [email protected] or [email protected] InformationSupplementary data are available at Bioinformatics online.

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