scholarly journals A Comparison for Dimensionality Reduction Methods of Single-Cell RNA-seq Data

2021 ◽  
Vol 12 ◽  
Author(s):  
Ruizhi Xiang ◽  
Wencan Wang ◽  
Lei Yang ◽  
Shiyuan Wang ◽  
Chaohan Xu ◽  
...  
Keyword(s):  
Dimensionality Reduction ◽  
Dimension Reduction ◽  
Single Cell ◽  
High Throughput Sequencing ◽  
Cellular Heterogeneity ◽  
Specific Situation ◽  
Rna Seq ◽  
Reduction Methods ◽  
The Stability ◽  
Downstream Analysis

Single-cell RNA sequencing (scRNA-seq) is a high-throughput sequencing technology performed at the level of an individual cell, which can have a potential to understand cellular heterogeneity. However, scRNA-seq data are high-dimensional, noisy, and sparse data. Dimension reduction is an important step in downstream analysis of scRNA-seq. Therefore, several dimension reduction methods have been developed. We developed a strategy to evaluate the stability, accuracy, and computing cost of 10 dimensionality reduction methods using 30 simulation datasets and five real datasets. Additionally, we investigated the sensitivity of all the methods to hyperparameter tuning and gave users appropriate suggestions. We found that t-distributed stochastic neighbor embedding (t-SNE) yielded the best overall performance with the highest accuracy and computing cost. Meanwhile, uniform manifold approximation and projection (UMAP) exhibited the highest stability, as well as moderate accuracy and the second highest computing cost. UMAP well preserves the original cohesion and separation of cell populations. In addition, it is worth noting that users need to set the hyperparameters according to the specific situation before using the dimensionality reduction methods based on non-linear model and neural network.

scholarly journals RgCop-A regularized copula based method for gene selection in single cell rna-seq data

2021 ◽  
Vol 17 (10) ◽  
pp. e1009464
Author(s):  
Snehalika Lall ◽  
Sumanta Ray ◽  
Sanghamitra Bandyopadhyay
Keyword(s):  
Single Cell ◽  
Gene Selection ◽  
Real Life ◽  
Classification Performance ◽  
Rna Seq ◽  
Scale Invariant ◽  
Dependence Measure ◽  
Highly Expressed Genes ◽  
The Stability ◽  
Downstream Analysis

Gene selection in unannotated large single cell RNA sequencing (scRNA-seq) data is important and crucial step in the preliminary step of downstream analysis. The existing approaches are primarily based on high variation (highly variable genes) or significant high expression (highly expressed genes) failed to provide stable and predictive feature set due to technical noise present in the data. Here, we propose RgCop, a novel regularized copula based method for gene selection from large single cell RNA-seq data. RgCop utilizes copula correlation (Ccor), a robust equitable dependence measure that captures multivariate dependency among a set of genes in single cell expression data. We raise an objective function by adding a l1 regularization term with Ccor to penalizes the redundant co-efficient of features/genes, resulting non-redundant effective features/genes set. Results show a significant improvement in the clustering/classification performance of real life scRNA-seq data over the other state-of-the-art. RgCop performs extremely well in capturing dependence among the features of noisy data due to the scale invariant property of copula, thereby improving the stability of the method. Moreover, the differentially expressed (DE) genes identified from the clusters of scRNA-seq data are found to provide an accurate annotation of cells. Finally, the features/genes obtained from RgCop can able to annotate the unknown cells with high accuracy.

scholarly journals NDRindex: a method for the quality assessment of single-cell RNA-Seq preprocessing data

2020 ◽  
Vol 21 (S16) ◽  
Author(s):  
Ruiyu Xiao ◽  
Guoshan Lu ◽  
Wanqian Guo ◽  
Shuilin Jin
Keyword(s):  
Dimensionality Reduction ◽  
Data Quality ◽  
Single Cell ◽  
Enrichment Analysis ◽  
Cell Types ◽  
Size Reduction ◽  
Rna Seq ◽  
Reduction Methods ◽  
The Many

Abstract Background Single-cell RNA sequencing can be used to fairly determine cell types, which is beneficial to the medical field, especially the many recent studies on COVID-19. Generally, single-cell RNA data analysis pipelines include data normalization, size reduction, and unsupervised clustering. However, different normalization and size reduction methods will significantly affect the results of clustering and cell type enrichment analysis. Choices of preprocessing paths is crucial in scRNA-Seq data mining, because a proper preprocessing path can extract more important information from complex raw data and lead to more accurate clustering results. Results We proposed a method called NDRindex (Normalization and Dimensionality Reduction index) to evaluate data quality of outcomes of normalization and dimensionality reduction methods. The method includes a function to calculate the degree of data aggregation, which is the key to measuring data quality before clustering. For the five single-cell RNA sequence datasets we tested, the results proved the efficacy and accuracy of our index. Conclusions This method we introduce focuses on filling the blanks in the selection of preprocessing paths, and the result proves its effectiveness and accuracy. Our research provides useful indicators for the evaluation of RNA-Seq data.

scholarly journals Exploring dimension-reduced embeddings with Sleepwalk

2019 ◽  
Author(s):  
Svetlana Ovchinnikova ◽  
Simon Anders
Keyword(s):  
Big Data ◽  
Dimension Reduction ◽  
Single Cell ◽  
Single Cells ◽  
High Dimensional ◽  
Rna Seq ◽  
Mouse Cursor ◽  
Sample Data ◽  
Reduction Methods ◽  
Full Power

AbstractDimension-reduction methods, such as t-SNE or UMAP, are widely used when exploring high-dimensional data describing many entities, e.g., RNA-seq data for many single cells. However, dimension reduction is commonly prone to introducing artefacts, and we hence need means to see where a dimension-reduced embedding is a faithful representation of the local neighbourhood and where it is not.We present Sleepwalk, a simple but powerful tool that allows the user to interactively explore an embedding, using colour to depict original or any other distances from all points to the cell under the mouse cursor. We show how this approach not only highlights distortions, but also reveals otherwise hidden characteristics of the data, and how Sleep-walk’s comparative modes help integrate multi-sample data and understand differences between embedding and preprocessing methods. Sleepwalk is a versatile and intuitive tool that unlocks the full power of dimension reduction and will be of value not only in single-cell RNA-seq but also in any other area with matrix-shaped big data.

scholarly journals Tuning parameters of dimensionality reduction methods for single-cell RNA-seq analysis

2020 ◽  
Author(s):  
Felix Raimundo ◽  
Celine Vallot ◽  
Jean Philippe Vert
Keyword(s):  
Dimensionality Reduction ◽  
Single Cell ◽  
Biological Diversity ◽  
Unmet Need ◽  
Principal Component ◽  
Parameter Tuning ◽  
Differential Analysis ◽  
Rna Seq ◽  
Reduction Methods ◽  
Complex Models

AbstractBackgroundMany computational methods have been developed recently to analyze single-cell RNA-seq (scRNA-seq) data. Several benchmark studies have compared these methods on their ability for dimensionality reduction, clustering or differential analysis, often relying on default parameters. Yet given the biological diversity of scRNA-seq datasets, parameter tuning might be essential for the optimal usage of methods, and determining how to tune parameters remains an unmet need.ResultsHere, we propose a benchmark to assess the performance of five methods, systematically varying their tunable parameters, for dimension reduction of scRNA-seq data, a common first step to many downstream applications such as cell type identification or trajectory inference. We run a total of 1.5 million experiments to assess the influence of parameter changes on the performance of each method, and propose two strategies to automatically tune parameters for methods that need it.ConclusionsWe find that principal component analysis (PCA)-based methods like scran and Seurat are competitive with default parameters but do not benefit much from parameter tuning, while more complex models like ZinbWave, DCA and scVI can reach better performance but after parameter tuning.

scholarly journals ZIFA: Dimensionality reduction for zero-inflated single cell gene expression analysis

2015 ◽  
Author(s):  
Christopher Yau ◽  
Emma Pierson
Keyword(s):  
Dimensionality Reduction ◽  
Single Cell ◽  
Rna Seq ◽  
Reduction Methods ◽  
Cell Gene Expression ◽  
High Dimensional Datasets ◽  
Cell Gene ◽  
Normal Cellular Function ◽  
Insight Into ◽  
Dimensionality Reduction Method

Single cell RNA-seq data allows insight into normal cellular function and diseases including cancer through the molecular characterisation of cellular state at the single-cell level. Dimensionality reduction of such high-dimensional datasets is essential for visualization and analysis, but single-cell RNA-seq data is challenging for classical dimensionality reduction methods because of the prevalence of dropout events leading to zero-inflated data. Here we develop a dimensionality reduction method, (Z)ero (I)nflated (F)actor (A)nalysis (ZIFA), which explicitly models the dropout characteristics, and show that it improves performance on simulated and biological datasets.

scholarly journals sc-REnF:An entropy guided robust feature selection for clustering of single-cell rna-seq data

2020 ◽  
Author(s):  
Snehalika Lall ◽  
Abhik Ghosh ◽  
Sumanta Ray ◽  
Sanghamitra Bandyopadhyay
Keyword(s):  
Single Cell ◽  
Gene Selection ◽  
Rna Seq ◽  
Technical Noise ◽  
Marker Selection ◽  
Cell Clustering ◽  
Typing Methods ◽  
Original Application ◽  
Downstream Analysis ◽  
Cell Typing

ABSTRACTMany single-cell typing methods require pure clustering of cells, which is susceptible towards the technical noise, and heavily dependent on high quality informative genes selected in the preliminary steps of downstream analysis. Techniques for gene selection in single-cell RNA sequencing (scRNA-seq) data are seemingly simple which casts problems with respect to the resolution of (sub-)types detection, marker selection and ultimately impacts towards cell annotation. We introduce sc-REnF, a novel and robust entropy based feature (gene) selection method, which leverages the landmark advantage of ‘Renyi’ and ‘Tsallis’ entropy achieved in their original application, in single cell clustering. Thereby, gene selection is robust and less sensitive towards the technical noise present in the data, producing a pure clustering of cells, beyond classifying independent and unknown sample with utmost accuracy. The corresponding software is available at: https://github.com/Snehalikalall/sc-REnF

scholarly journals Enhancing droplet-based single-nucleus RNA-seq resolution using the semi-supervised machine learning classifier DIEM

2019 ◽  
Author(s):  
Marcus Alvarez ◽  
Elior Rahmani ◽  
Brandon Jew ◽  
Kristina M. Garske ◽  
Zong Miao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Cell Types ◽  
Supervised Machine Learning ◽  
Data Sets ◽  
Rna Seq ◽  
Novel Approach ◽  
Single Nucleus ◽  
Downstream Analysis

AbstractSingle-nucleus RNA sequencing (snRNA-seq) measures gene expression in individual nuclei instead of cells, allowing for unbiased cell type characterization in solid tissues. Contrary to single-cell RNA seq (scRNA-seq), we observe that snRNA-seq is commonly subject to contamination by high amounts of extranuclear background RNA, which can lead to identification of spurious cell types in downstream clustering analyses if overlooked. We present a novel approach to remove debris-contaminated droplets in snRNA-seq experiments, called Debris Identification using Expectation Maximization (DIEM). Our likelihood-based approach models the gene expression distribution of debris and cell types, which are estimated using EM. We evaluated DIEM using three snRNA-seq data sets: 1) human differentiating preadipocytes in vitro, 2) fresh mouse brain tissue, and 3) human frozen adipose tissue (AT) from six individuals. All three data sets showed various degrees of extranuclear RNA contamination. We observed that existing methods fail to account for contaminated droplets and led to spurious cell types. When compared to filtering using these state of the art methods, DIEM better removed droplets containing high levels of extranuclear RNA and led to higher quality clusters. Although DIEM was designed for snRNA-seq data, we also successfully applied DIEM to single-cell data. To conclude, our novel method DIEM removes debris-contaminated droplets from single-cell-based data fast and effectively, leading to cleaner downstream analysis. Our code is freely available for use at https://github.com/marcalva/diem.

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