CIDER: an interpretable meta-clustering framework for single-cell RNA-seq data integration and evaluation.
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ABSTRACT:
SUBMITTER: Hu Z
PROVIDER: S-EPMC8667531 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:With the recent proliferation of single-cell RNA-Seq experiments, several methods have been developed for unsupervised analysis of the resulting datasets. These methods often rely on unintuitive hyperparameters and do not explicitly address the subjectivity associated with clustering. RESULTS:In this work, we present DendroSplit, an interpretable framework for analyzing single-cell RNA-Seq datasets that addresses both the clustering interpretability and clustering subjectivity issues. DendroSplit offers a novel perspective on the single-cell RNA-Seq clustering problem motivated by the definition of "cell type", allowing us to cluster using feature selection to uncover multiple levels of biologically meaningful populations in the data. We analyze several landmark single-cell datasets, demonstrating both the method's efficacy and computational efficiency. CONCLUSION:DendroSplit offers a clustering framework that is comparable to existing methods in terms of accuracy and speed but is novel in its emphasis on interpretabilty. We provide the full DendroSplit software package at https://github.com/jessemzhang/dendrosplit .
| S-EPMC5845381 | biostudies-literature
Project description:Subpopulation identification, usually via some form of unsupervised clustering, is a fundamental step in the analysis of many single-cell RNA-seq data sets. This has motivated the development and application of a broad range of clustering methods, based on various underlying algorithms. Here, we provide a systematic and extensible performance evaluation of 14 clustering algorithms implemented in R, including both methods developed explicitly for scRNA-seq data and more general-purpose methods. The methods were evaluated using nine publicly available scRNA-seq data sets as well as three simulations with varying degree of cluster separability. The same feature selection approaches were used for all methods, allowing us to focus on the investigation of the performance of the clustering algorithms themselves. We evaluated the ability of recovering known subpopulations, the stability and the run time and scalability of the methods. Additionally, we investigated whether the performance could be improved by generating consensus partitions from multiple individual clustering methods. We found substantial differences in the performance, run time and stability between the methods, with SC3 and Seurat showing the most favorable results. Additionally, we found that consensus clustering typically did not improve the performance compared to the best of the combined methods, but that several of the top-performing methods already perform some type of consensus clustering. All the code used for the evaluation is available on GitHub ( https://github.com/markrobinsonuzh/scRNAseq_clustering_comparison). In addition, an R package providing access to data and clustering results, thereby facilitating inclusion of new methods and data sets, is available from Bioconductor ( https://bioconductor.org/packages/DuoClustering2018).
| S-EPMC6134335 | biostudies-literature
Project description:MOTIVATION:Single-cell RNA-seq makes possible the investigation of variability in gene expression among cells, and dependence of variation on cell type. Statistical inference methods for such analyses must be scalable, and ideally interpretable. RESULTS:We present an approach based on a modification of a recently published highly scalable variational autoencoder framework that provides interpretability without sacrificing much accuracy. We demonstrate that our approach enables identification of gene programs in massive datasets. Our strategy, namely the learning of factor models with the auto-encoding variational Bayes framework, is not domain specific and may be useful for other applications. AVAILABILITY AND IMPLEMENTATION:The factor model is available in the scVI package hosted at https://github.com/YosefLab/scVI/. CONTACT:v@nxn.se. SUPPLEMENTARY INFORMATION:Supplementary data are available at Bioinformatics online.
| S-EPMC7267837 | biostudies-literature
Project description:MotivationAccurately clustering cell types from a mass of heterogeneous cells is a crucial first step for the analysis of single-cell RNA-seq (scRNA-Seq) data. Although several methods have been recently developed, they utilize different characteristics of data and yield varying results in terms of both the number of clusters and actual cluster assignments.ResultsHere, we present SAFE-clustering, single-cell aggregated (From Ensemble) clustering, a flexible, accurate and robust method for clustering scRNA-Seq data. SAFE-clustering takes as input, results from multiple clustering methods, to build one consensus solution. SAFE-clustering currently embeds four state-of-the-art methods, SC3, CIDR, Seurat and t-SNE + k-means; and ensembles solutions from these four methods using three hypergraph-based partitioning algorithms. Extensive assessment across 12 datasets with the number of clusters ranging from 3 to 14, and the number of single cells ranging from 49 to 32, 695 showcases the advantages of SAFE-clustering in terms of both cluster number (18.2-58.1% reduction in absolute deviation to the truth) and cluster assignment (on average 36.0% improvement, and up to 18.5% over the best of the four methods, measured by adjusted rand index). Moreover, SAFE-clustering is computationally efficient to accommodate large datasets, taking <10 min to process 28 733 cells.Availability and implementationSAFEclustering, including source codes and tutorial, is freely available at https://github.com/yycunc/SAFEclustering.Supplementary informationSupplementary data are available at Bioinformatics online.
| S-EPMC6477982 | biostudies-literature
Project description:Single-cell RNA-seq enables the quantitative characterization of cell types based on global transcriptome profiles. We present single-cell consensus clustering (SC3), a user-friendly tool for unsupervised clustering, which achieves high accuracy and robustness by combining multiple clustering solutions through a consensus approach (http://bioconductor.org/packages/SC3). We demonstrate that SC3 is capable of identifying subclones from the transcriptomes of neoplastic cells collected from patients.
| S-EPMC5410170 | biostudies-literature
Project description:Single-cell RNA sequencing (scRNA-seq) technologies allow numerous opportunities for revealing novel and potentially unexpected biological discoveries. scRNA-seq clustering helps elucidate cell-to-cell heterogeneity and uncover cell subgroups and cell dynamics at the group level. Two important aspects of scRNA-seq data analysis were introduced and discussed in the present review: relevant datasets and analytical tools. In particular, we reviewed popular scRNA-seq datasets and discussed scRNA-seq clustering models including K-means clustering, hierarchical clustering, consensus clustering, and so on. Seven state-of-the-art scRNA clustering methods were compared on five public available datasets. Two primary evaluation metrics, the Adjusted Rand Index (ARI) and the Normalized Mutual Information (NMI), were used to evaluate these methods. Although unsupervised models can effectively cluster scRNA-seq data, these methods also have challenges. Some suggestions were provided for future research directions.
| S-EPMC7549635 | biostudies-literature
Project description:Cell clustering is one of the most important and commonly performed tasks in single-cell RNA sequencing (scRNA-seq) data analysis. An important step in cell clustering is to select a subset of genes (referred to as 'features'), whose expression patterns will then be used for downstream clustering. A good set of features should include the ones that distinguish different cell types, and the quality of such set could have a significant impact on the clustering accuracy. All existing scRNA-seq clustering tools include a feature selection step relying on some simple unsupervised feature selection methods, mostly based on the statistical moments of gene-wise expression distributions. In this work, we carefully evaluate the impact of feature selection on cell clustering accuracy. In addition, we develop a feature selection algorithm named FEAture SelecTion (FEAST), which provides more representative features. We apply the method on 12 public scRNA-seq datasets and demonstrate that using features selected by FEAST with existing clustering tools significantly improve the clustering accuracy.
| S-EPMC8644062 | biostudies-literature
Project description:Single-cell computational pipelines involve two critical steps: organizing cells (clustering) and identifying the markers driving this organization (differential expression analysis). State-of-the-art pipelines perform differential analysis after clustering on the same dataset. We observe that because clustering "forces" separation, reusing the same dataset generates artificially low p values and hence false discoveries. We introduce a valid post-clustering differential analysis framework, which corrects for this problem. We provide software at https://github.com/jessemzhang/tn_test.
| S-EPMC7202736 | biostudies-literature
Project description:MotivationSingle-cell RNA sequencing has emerged as a powerful technology for studying gene expression at the individual cell level. Clustering individual cells into distinct subpopulations is fundamental in scRNA-seq data analysis, facilitating the identification of cell types and exploration of cellular heterogeneity. Despite the recent development of many deep learning-based single-cell clustering methods, few have effectively exploited the correlations among genes, resulting in suboptimal clustering outcomes.ResultsHere, we propose a novel masked autoencoder-based method, scMAE, for cell clustering. scMAE perturbs gene expression and employs a masked autoencoder to reconstruct the original data, learning robust and informative cell representations. The masked autoencoder introduces a masking predictor, which captures relationships among genes by predicting whether gene expression values are masked. By integrating this masking mechanism, scMAE effectively captures latent structures and dependencies in the data, enhancing clustering performance. We conducted extensive comparative experiments using various clustering evaluation metrics on 15 scRNA-seq datasets from different sequencing platforms. Experimental results indicate that scMAE outperforms other state-of-the-art methods on these datasets. In addition, scMAE accurately identifies rare cell types, which are challenging to detect due to their low abundance. Furthermore, biological analyses confirm the biological significance of the identified cell subpopulations.Availability and implementationThe source code of scMAE is available at: https://zenodo.org/records/10465991.
| S-EPMC10832357 | biostudies-literature
Project description:The latest progresses of experimental biology have generated a large number of data with different formats and lengths. Deep learning is an ideal tool to deal with complex datasets, but its inherent "black box" nature needs more interpretability. At the same time, traditional interpretable machine learning methods, such as linear regression or random forest, could only deal with numerical features instead of modular features often encountered in the biological field. Here, we present MultiCapsNet (https://github.com/wanglf19/MultiCapsNet), a new deep learning model built on CapsNet and scCapsNet, which possesses the merits such as easy data integration and high model interpretability. To demonstrate the ability of this model as an interpretable classifier to deal with modular inputs, we test MultiCapsNet on three datasets with different data type and application scenarios. Firstly, on the labeled variant call dataset, MultiCapsNet shows a similar classification performance with neural network model, and provides importance scores for data sources directly without an extra importance determination step required by the neural network model. The importance scores generated by these two models are highly correlated. Secondly, on single cell RNA sequence (scRNA-seq) dataset, MultiCapsNet integrates information about protein-protein interaction (PPI), and protein-DNA interaction (PDI). The classification accuracy of MultiCapsNet is comparable to the neural network and random forest model. Meanwhile, MultiCapsNet reveals how each transcription factor (TF) or PPI cluster node contributes to classification of cell type. Thirdly, we made a comparison between MultiCapsNet and SCENIC. The results show several cell type relevant TFs identified by both methods, further proving the validity and interpretability of the MultiCapsNet.
| S-EPMC8652257 | biostudies-literature