Model-based deep embedding for constrained clustering analysis of single cell RNA-seq data.
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ABSTRACT:
SUBMITTER: Tian T
PROVIDER: S-EPMC7994574 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Spatially resolved scRNA-seq (sp-scRNA-seq) technologies provide the potential to comprehensively profile gene expression patterns in tissue context. However, the development of computational methods lags behind the advances in these technologies, which limits the fulfillment of their potential. In this study, we develop a deep learning approach for clustering sp-scRNA-seq data, named Deep Spatially constrained Single-cell Clustering (DSSC). In this model, we integrate the spatial information of cells into the clustering process in two steps: (1) the spatial information is encoded by using a graphical neural network model, and (2) cell-to-cell constraints are built based on the spatial expression pattern of the marker genes and added in the model to guide the clustering process. Then, a deep embedding clustering is performed on the bottleneck layer of autoencoder by Kullback-Leibler (KL) divergence along with the learning of feature representation. DSSC is the first model that can use information from both spatial coordinates and marker genes to guide cell/spot clustering. Extensive experiments on both simulated and real data sets show that DSSC boosts clustering performance significantly compared with the state-of-the-art methods. It has robust performance across different data sets with various cell type/tissue organization and/or cell type/tissue spatial dependency. We conclude that DSSC is a promising tool for clustering sp-scRNA-seq data.
| S-EPMC9712636 | biostudies-literature
Project description:Single cell RNA-seq (scRNA-seq) techniques can reveal valuable insights of cell-to-cell heterogeneities. Projection of high-dimensional data into a low-dimensional subspace is a powerful strategy in general for mining such big data. However, scRNA-seq suffers from higher noise and lower coverage than traditional bulk RNA-seq, hence bringing in new computational difficulties. One major challenge is how to deal with the frequent drop-out events. The events, usually caused by the stochastic burst effect in gene transcription and the technical failure of RNA transcript capture, often render traditional dimension reduction methods work inefficiently. To overcome this problem, we have developed a novel Single Cell Representation Learning (SCRL) method based on network embedding. This method can efficiently implement data-driven non-linear projection and incorporate prior biological knowledge (such as pathway information) to learn more meaningful low-dimensional representations for both cells and genes. Benchmark results show that SCRL outperforms other dimensional reduction methods on several recent scRNA-seq datasets.
| S-EPMC5737094 | biostudies-literature
Project description:Cluster analysis is a crucial stage in the analysis and interpretation of single-cell gene expression (scRNA-seq) data. It is an inherently ill-posed problem whose solutions depend heavily on hyper-parameter and algorithmic choice. The popular approach of K-means clustering, for example, depends heavily on the choice of K and the convergence of the expectation-maximization algorithm to local minima of the objective. Exhaustive search of the space for multiple good quality solutions is known to be a complex problem. Here, we show that quantum computing offers a solution to exploring the cost function of clustering by quantum annealing, implemented on a quantum computing facility offered by D-Wave [1]. Out formulation extracts minimum vertex cover of an affinity graph to sub-sample the cell population and quantum annealing to optimise the cost function. A distribution of low-energy solutions can thus be extracted, offering alternate hypotheses about how genes group together in their space of expressions.
| S-EPMC10597635 | biostudies-literature
Project description:Single-cell RNA-seq data contain a large proportion of zeros for expressed genes. Such dropout events present a fundamental challenge for various types of data analyses. Here, we describe the SCRABBLE algorithm to address this problem. SCRABBLE leverages bulk data as a constraint and reduces unwanted bias towards expressed genes during imputation. Using both simulation and several types of experimental data, we demonstrate that SCRABBLE outperforms the existing methods in recovering dropout events, capturing true distribution of gene expression across cells, and preserving gene-gene relationship and cell-cell relationship in the data.
| S-EPMC6501316 | biostudies-literature
Project description:Single-cell RNA-Seq (scRNA-seq) is invaluable for studying biological systems. Dimensionality reduction is a crucial step in interpreting the relation between cells in scRNA-seq data. However, current dimensionality reduction methods are often confounded by multiple simultaneous technical and biological variability, result in "crowding" of cells in the center of the latent space, or inadequately capture temporal relationships. Here, we introduce scPhere, a scalable deep generative model to embed cells into low-dimensional hyperspherical or hyperbolic spaces to accurately represent scRNA-seq data. ScPhere addresses multi-level, complex batch factors, facilitates the interactive visualization of large datasets, resolves cell crowding, and uncovers temporal trajectories. We demonstrate scPhere on nine large datasets in complex tissue from human patients or animal development. Our results show how scPhere facilitates the interpretation of scRNA-seq data by generating batch-invariant embeddings to map data from new individuals, identifies cell types affected by biological variables, infers cells' spatial positions in pre-defined biological specimens, and highlights complex cellular relations.
| S-EPMC8099904 | biostudies-literature
Project description:Quality control, global biases, normalization, and analysis methods for RNA-Seq data are quite different than those for microarray-based studies. The assumption of normality is reasonable for microarray based gene expression data; however, RNA-Seq data tend to follow an over-dispersed Poisson or negative binomial distribution. Little research has been done to assess how data transformations impact Gaussian model-based clustering with respect to clustering performance and accuracy in estimating the correct number of clusters in RNA-Seq data. In this article, we investigate Gaussian model-based clustering performance and accuracy in estimating the correct number of clusters by applying four data transformations (i.e., naïve, logarithmic, Blom, and variance stabilizing transformation) to simulated RNA-Seq data. To do so, an extensive simulation study was carried out in which the scenarios varied in terms of: how genes were selected to be included in the clustering analyses, size of the clusters, and number of clusters. Following the application of the different transformations to the simulated data, Gaussian model-based clustering was carried out. To assess clustering performance for each of the data transformations, the adjusted rand index, clustering error rate, and concordance index were utilized. As expected, our results showed that clustering performance was gained in scenarios where data transformations were applied to make the data appear "more" Gaussian in distribution.
| S-EPMC5828440 | 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: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:BackgroundAdvances 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.ResultsWe 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.ConclusionThe 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.
| S-EPMC7541255 | biostudies-literature
Project description:Advances in technology have made it convenient to obtain a large amount of single cell RNA sequencing (scRNA-seq) data. Since that clustering is a very important step in identifying or defining cellular phenotypes, many clustering approaches have been developed recently for these applications. The general methods can be roughly divided into normal clustering methods and integrated (ensemble) clustering methods which combine more than two normal clustering methods aiming to get much more informative performance. In order to make a contrast with the integrated clustering algorithm, the normal clustering method is often called individual or base clustering method. Note that the results of many individual clustering methods are often developed to capture one aspect of the data, and the results depend on the initial parameter settings, such as cluster number, distance metric and so on. Compared with individual clustering, although integrative clustering method may get much more accurate performance, the results depend on the base clustering results and integrated systems are often not self-regulation. Therefore, how to design a robust unsupervised clustering method is still a challenge. In order to tackle above limitations, we propose a novel Ensemble Clustering algorithm based on Probability Graphical Model with Graph Regularization, which is called EC-PGMGR for short. On one hand, we use parameter controlling in Probability Graphical Model (PGM) to automatically determine the cluster number without prior knowledge. On the other hand, we add a regularization term to reduce the effect deriving from some weak base clustering results. Particularly, the integrative results collected from base clustering methods can be assembled in the form of combination with self-regulation weights through a pre-learning process, which can efficiently enhance the effect of active clustering methods while weaken the effect of inactive clustering methods. Experiments are carried out on 7 data sets generated by different platforms with the number of single cells from 822 to 5,132. Results show that EC-PGMGR performs better than 4 alternative individual clustering methods and 2 ensemble methods in terms of accuracy including Adjusted Rand Index (ARI) and Normalized Mutual Information (NMI), robustness, effectiveness and so on. EC-PGMGR provides an effective way to integrate different clustering results for more accurate and reliable results in further biological analysis as well. It may provide some new insights to the other applications of clustering.
| S-EPMC7673820 | biostudies-literature