ScSTEM: clustering pseudotime ordered single-cell data.
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ABSTRACT:
SUBMITTER: Song Q
PROVIDER: S-EPMC9264648 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Pseudotime analysis from scRNA-seq data enables to characterize the continuous progression of various biological processes, such as the cell cycle. Cell cycle plays an important role in cell fate decisions and differentiation and is often regarded as a confounder in scRNA-seq data analysis when analyzing the role of other factors. Therefore, accurate prediction of cell cycle pseudotime and identification of cell cycle stages are important steps for characterizing the development-related biological processes. Here, we develop CCPE, a novel cell cycle pseudotime estimation method to characterize cell cycle timing and identify cell cycle phases from scRNA-seq data. CCPE uses a discriminative helix to characterize the circular process of the cell cycle and estimates each cell's pseudotime along the cell cycle. We evaluated the performance of CCPE based on a variety of simulated and real scRNA-seq datasets. Our results indicate that CCPE is an effective method for cell cycle estimation and competitive in various applications compared with other existing methods. CCPE successfully identified cell cycle marker genes and is robust to dropout events in scRNA-seq data. Accurate prediction of the cell cycle using CCPE can also effectively facilitate the removal of cell cycle effects across cell types or conditions.
| S-EPMC8789092 | biostudies-literature
Project description:MotivationImprovements in single-cell RNA-seq technologies mean that studies measuring multiple experimental conditions, such as time series, have become more common. At present, few computational methods exist to infer time series-specific transcriptome changes, and such studies have therefore typically used unsupervised pseudotime methods. While these methods identify cell subpopulations and the transitions between them, they are not appropriate for identifying the genes that vary coherently along the time series. In addition, the orderings they estimate are based only on the major sources of variation in the data, which may not correspond to the processes related to the time labels.ResultsWe introduce psupertime, a supervised pseudotime approach based on a regression model, which explicitly uses time-series labels as input. It identifies genes that vary coherently along a time series, in addition to pseudotime values for individual cells, and a classifier that can be used to estimate labels for new data with unknown or differing labels. We show that psupertime outperforms benchmark classifiers in terms of identifying time-varying genes and provides better individual cell orderings than popular unsupervised pseudotime techniques. psupertime is applicable to any single-cell RNA-seq dataset with sequential labels (e.g. principally time series but also drug dosage and disease progression), derived from either experimental design and provides a fast, interpretable tool for targeted identification of genes varying along with specific biological processes.Availability and implementationR package available at github.com/wmacnair/psupertime and code for results reproduction at github.com/wmacnair/psupplementary.Supplementary informationSupplementary data are available at Bioinformatics online.
| S-EPMC9235474 | biostudies-literature
Project description:Motivated by the dynamics of development, in which cells of recognizable types, or pure cell types, transition into other types over time, we propose a method of semisoft clustering that can classify both pure and intermediate cell types from data on gene expression from individual cells. Called semisoft clustering with pure cells (SOUP), this algorithm reveals the clustering structure for both pure cells and transitional cells with soft memberships. SOUP involves a two-step process: Identify the set of pure cells and then estimate a membership matrix. To find pure cells, SOUP uses the special block structure in the expression similarity matrix. Once pure cells are identified, they provide the key information from which the membership matrix can be computed. By modeling cells as a continuous mixture of K discrete types we obtain more parsimonious results than obtained with standard clustering algorithms. Moreover, using soft membership estimates of cell type cluster centers leads to better estimates of developmental trajectories. The strong performance of SOUP is documented via simulation studies, which show its robustness to violations of modeling assumptions. The advantages of SOUP are illustrated by analyses of two independent datasets of gene expression from a large number of cells from fetal brain.
| S-EPMC6329952 | biostudies-literature
Project description:MotivationRepeated cross-sectional time series single cell data confound several sources of variation, with contributions from measurement noise, stochastic cell-to-cell variation and cell progression at different rates. Time series from single cell assays are particularly susceptible to confounding as the measurements are not averaged over populations of cells. When several genes are assayed in parallel these effects can be estimated and corrected for under certain smoothness assumptions on cell progression.ResultsWe present a principled probabilistic model with a Bayesian inference scheme to analyse such data. We demonstrate our method's utility on public microarray, nCounter and RNA-seq datasets from three organisms. Our method almost perfectly recovers withheld capture times in an Arabidopsis dataset, it accurately estimates cell cycle peak times in a human prostate cancer cell line and it correctly identifies two precocious cells in a study of paracrine signalling in mouse dendritic cells. Furthermore, our method compares favourably with Monocle, a state-of-the-art technique. We also show using held-out data that uncertainty in the temporal dimension is a common confounder and should be accounted for in analyses of repeated cross-sectional time series.Availability and implementationOur method is available on CRAN in the DeLorean package.Contactjohn.reid@mrc-bsu.cam.ac.ukSupplementary informationSupplementary data are available at Bioinformatics online.
| S-EPMC5039927 | 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:Summary:To construct gene co-expression networks based on single-cell RNA-Sequencing data, we present an algorithm called LEAP, which utilizes the estimated pseudotime of the cells to find gene co-expression that involves time delay. Availability and Implementation:R package LEAP available on CRAN. Contact:jun.li@nd.edu. Supplementary information:Supplementary data are available at Bioinformatics online.
| S-EPMC5860270 | biostudies-literature
Project description:SummaryscFates provides an extensive toolset for the analysis of dynamic trajectories comprising tree learning, feature association testing, branch differential expression and with a focus on cell biasing and fate splits at the level of bifurcations. It is meant to be fully integrated into the scanpy ecosystem for seamless analysis of trajectories from single-cell data of various modalities (e.g. RNA and ATAC).Availability and implementationscFates is released as open-source software under the BSD 3-Clause 'New' License and is available from the Python Package Index at https://pypi.org/project/scFates/. The source code is available on GitHub at https://github.com/LouisFaure/scFates/. Code reproduction and tutorials on published datasets are available on GitHub at https://github.com/LouisFaure/scFates_notebooks.Supplementary informationSupplementary data are available at Bioinformatics online.
| S-EPMC9805561 | biostudies-literature
Project description:BACKGROUND:Single-cell transcriptomics allows researchers to investigate complex communities of heterogeneous cells. It can be applied to stem cells and their descendants in order to chart the progression from multipotent progenitors to fully differentiated cells. While a variety of statistical and computational methods have been proposed for inferring cell lineages, the problem of accurately characterizing multiple branching lineages remains difficult to solve. RESULTS:We introduce Slingshot, a novel method for inferring cell lineages and pseudotimes from single-cell gene expression data. In previously published datasets, Slingshot correctly identifies the biological signal for one to three branching trajectories. Additionally, our simulation study shows that Slingshot infers more accurate pseudotimes than other leading methods. CONCLUSIONS:Slingshot is a uniquely robust and flexible tool which combines the highly stable techniques necessary for noisy single-cell data with the ability to identify multiple trajectories. Accurate lineage inference is a critical step in the identification of dynamic temporal gene expression.
| S-EPMC6007078 | biostudies-literature
Project description:MotivationSingle-cell multi-omics sequencing techniques have rapidly developed in the past few years. Clustering analysis with single-cell multi-omics data may give us novel perspectives to dissect cellular heterogeneity. However, multi-omics data have the properties of inherited large dimension, high sparsity and existence of doublets. Moreover, representations of different omics from even the same cell follow diverse distributions. Without proper distribution alignment techniques, clustering methods will encounter less separable clusters easily affected by less informative omics data.ResultsWe developed MoClust, a novel joint clustering framework that can be applied to several types of single-cell multi-omics data. A selective automatic doublet detection module that can identify and filter out doublets is introduced in the pretraining stage to improve data quality. Omics-specific autoencoders are introduced to characterize the multi-omics data. A contrastive learning way of distribution alignment is adopted to adaptively fuse omics representations into an omics-invariant representation. This novel way of alignment boosts the compactness and separableness of clusters, while accurately weighting the contribution of each omics to the clustering object. Extensive experiments, over both simulated and real multi-omics datasets, demonstrated the powerful alignment, doublet detection and clustering ability features of MoClust.Availability and implementationAn implementation of MoClust is available from https://doi.org/10.5281/zenodo.7306504.Supplementary informationSupplementary data are available at Bioinformatics online.
| S-EPMC9805570 | biostudies-literature
Project description:Recent advances in bioinformatics analyses have led to the development of novel tools enabling the capture and trajectory mapping of single-cell RNA sequencing (scRNAseq) data. However, there is a lack of methods to assess the contributions of biological pathways and transcription factors to an overall developmental trajectory mapped from scRNAseq data. In this manuscript, we present a simplified approach for trajectory inference of pathway significance (TIPS) that leverages existing knowledgebases of functional pathways and other gene lists to provide further mechanistic insights into a biological process. TIPS identifies key pathways which contribute to a process of interest, as well as the individual genes that best reflect these changes. TIPS also provides insight into the relative timing of pathway changes, as well as a suite of visualizations to enable simplified data interpretation of scRNAseq libraries generated using a wide range of techniques. The TIPS package can be run through either a web server or downloaded as a user-friendly GUI run in R, and may serve as a useful tool to help biologists perform deeper functional analyses and visualization of their single-cell data.
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