Single Cell Clustering with Sparse Similarity Matrix Learning

Author(s):  
Wenjing Zhang ◽  
Yuting Tan ◽  
Fang-Xiang Wu
2019 ◽  
Author(s):  
Na Yu ◽  
Jin-Xing Liu ◽  
Ying-Lian Gao ◽  
Chun-Hou Zheng ◽  
Junliang Shang ◽  
...  

AbstractThe development of single-cell RNA-sequencing (scRNA-seq) technology has enabled the measurement of gene expression in individual cells. This provides an unprecedented opportunity to explore the biological mechanisms at the cellular level. However, existing scRNA-seq analysis methods are susceptible to noise and outliers or ignore the manifold structure inherent in the data. In this paper, a novel method called Cauchy non-negative Laplacian regularized low-rank representation (CNLLRR) is proposed to alleviate the above problem. Specifically, we employ the Cauchy loss function (CLF) instead of the conventional norm constraints in the noise matrix of CNLLRR, which will enhance the robustness of the method. In addition, graph regularization term is applied to the objective function, which can capture the paired geometric relationships between cells. Then, alternating direction method of multipliers (ADMM) is adopted to solve the optimization problem of CNLLRR. Finally, extensive experiments on scRNA-seq data reveal that the proposed CNLLRR method outperforms other state-of-the-art methods for cell clustering, cell visualization and prioritization of gene markers. CNLLRR contributes to understand the heterogeneity between cell populations in complex biological systems.Author summaryAnalysis of single-cell data can help to further study the heterogeneity and complexity of cell populations. The current analysis methods are mainly to learn the similarity between cells and cells. Then they use the clustering algorithm to perform cell clustering or downstream analysis on the obtained similarity matrix. Therefore, constructing accurate cell-to-cell similarity is crucial for single-cell data analysis. In this paper, we design a novel Cauchy non-negative Laplacian regularized low-rank representation (CNLLRR) method to get a better similarity matrix. Specifically, Cauchy loss function (CLF) constraint is applied to punish noise matrix, which will improve the robustness of CNLLRR to noise and outliers. Moreover, graph regularization term is applied to the objective function, which will effectively encode the local manifold information of the data. Further, these will guarantee the quality of the cell-to-cell similarity matrix learned. Finally, single-cell data analysis experiments show that our method is superior to other representative methods.


2021 ◽  
Vol 1738 ◽  
pp. 012078
Author(s):  
Yaxuan Cui ◽  
Kunjie Luo ◽  
Zheyu Zhang ◽  
Saijia Liu

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Ryan B. Patterson-Cross ◽  
Ariel J. Levine ◽  
Vilas Menon

Abstract Background Generating and analysing single-cell data has become a widespread approach to examine tissue heterogeneity, and numerous algorithms exist for clustering these datasets to identify putative cell types with shared transcriptomic signatures. However, many of these clustering workflows rely on user-tuned parameter values, tailored to each dataset, to identify a set of biologically relevant clusters. Whereas users often develop their own intuition as to the optimal range of parameters for clustering on each data set, the lack of systematic approaches to identify this range can be daunting to new users of any given workflow. In addition, an optimal parameter set does not guarantee that all clusters are equally well-resolved, given the heterogeneity in transcriptomic signatures in most biological systems. Results Here, we illustrate a subsampling-based approach (chooseR) that simultaneously guides parameter selection and characterizes cluster robustness. Through bootstrapped iterative clustering across a range of parameters, chooseR was used to select parameter values for two distinct clustering workflows (Seurat and scVI). In each case, chooseR identified parameters that produced biologically relevant clusters from both well-characterized (human PBMC) and complex (mouse spinal cord) datasets. Moreover, it provided a simple “robustness score” for each of these clusters, facilitating the assessment of cluster quality. Conclusion chooseR is a simple, conceptually understandable tool that can be used flexibly across clustering algorithms, workflows, and datasets to guide clustering parameter selection and characterize cluster robustness.


2020 ◽  
Author(s):  
Snehalika Lall ◽  
Abhik Ghosh ◽  
Sumanta Ray ◽  
Sanghamitra Bandyopadhyay

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


2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Chunxiang Wang ◽  
Xin Gao ◽  
Juntao Liu

Abstract Background Advances in single-cell RNA-seq technology have led to great opportunities for the quantitative characterization of cell types, and many clustering algorithms have been developed based on single-cell gene expression. However, we found that different data preprocessing methods show quite different effects on clustering algorithms. Moreover, there is no specific preprocessing method that is applicable to all clustering algorithms, and even for the same clustering algorithm, the best preprocessing method depends on the input data. Results We designed a graph-based algorithm, SC3-e, specifically for discriminating the best data preprocessing method for SC3, which is currently the most widely used clustering algorithm for single cell clustering. When tested on eight frequently used single-cell RNA-seq data sets, SC3-e always accurately selects the best data preprocessing method for SC3 and therefore greatly enhances the clustering performance of SC3. Conclusion The SC3-e algorithm is practically powerful for discriminating the best data preprocessing method, and therefore largely enhances the performance of cell-type clustering of SC3. It is expected to play a crucial role in the related studies of single-cell clustering, such as the studies of human complex diseases and discoveries of new cell types.


2019 ◽  
Vol 35 (19) ◽  
pp. 3642-3650 ◽  
Author(s):  
Ruiqing Zheng ◽  
Min Li ◽  
Zhenlan Liang ◽  
Fang-Xiang Wu ◽  
Yi Pan ◽  
...  

Abstract Motivation The development of single-cell RNA-sequencing (scRNA-seq) provides a new perspective to study biological problems at the single-cell level. One of the key issues in scRNA-seq analysis is to resolve the heterogeneity and diversity of cells, which is to cluster the cells into several groups. However, many existing clustering methods are designed to analyze bulk RNA-seq data, it is urgent to develop the new scRNA-seq clustering methods. Moreover, the high noise in scRNA-seq data also brings a lot of challenges to computational methods. Results In this study, we propose a novel scRNA-seq cell type detection method based on similarity learning, called SinNLRR. The method is motivated by the self-expression of the cells with the same group. Specifically, we impose the non-negative and low rank structure on the similarity matrix. We apply alternating direction method of multipliers to solve the optimization problem and propose an adaptive penalty selection method to avoid the sensitivity to the parameters. The learned similarity matrix could be incorporated with spectral clustering, t-distributed stochastic neighbor embedding for visualization and Laplace score for prioritizing gene markers. In contrast to other scRNA-seq clustering methods, our method achieves more robust and accurate results on different datasets. Availability and implementation Our MATLAB implementation of SinNLRR is available at, https://github.com/zrq0123/SinNLRR. Supplementary information Supplementary data are available at Bioinformatics online.


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