Resolution of the curse of dimensionality in single-cell RNA-sequencing data analysis
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PROVIDER: PRJNA732704 | ENA |
REPOSITORIES: ENA
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Project description:Single-cell RNA sequencing (scRNA-seq) can determine gene expression in numerous individual cells simultaneously, promoting progress in the biomedical sciences. However, scRNA-seq data are high-dimensional with substantial technical noise, including dropouts. During analysis of scRNA-seq data, such noise engenders a statistical problem known as the curse of dimensionality (COD). Based on high-dimensional statistics, we herein formulate a noise reduction method, RECODE (resolution of the curse of dimensionality), for high-dimensional data with random sampling noise. We show that RECODE consistently resolves COD in relevant scRNA-seq data with unique molecular identifiers. RECODE does not involve dimension reduction and recovers expression values for all genes, including lowly expressed genes, realizing precise delineation of cell-fate transitions and identification of rare cells with all gene information. Compared to representative imputation methods, RECODE employs different principles and exhibits superior overall performance in cell-clustering, expression-value recovery, and single-cell level analysis. The RECODE algorithm is parameter-free, data-driven, deterministic, and high-speed, and its applicability can be predicted based on the variance normalization performance. We propose RECODE as a powerful strategy for preprocessing noisy high-dimensional data.
2022-08-04 | GSE175525 | GEO
Project description:De novo analysis of bulk RNA-seq data at spatially resolved single-cell resolution
| PRJNA794115 | ENA
Project description:Single-cell RNA-sequencing (scRNA-seq) techniques provide unprecedented opportunities to investigate phenotypic and molecular heterogeneity in complex biological systems. However, profiling massive amounts of cells brings great computational challenges to accurately and efficiently characterize diverse cell populations. Single cell discriminant analysis (scDA) solves this problem by simultaneously identifying cell groups and discriminant metagenes based on the construction of cell-by-cell representation graph, and then using them to annotate unlabeled cells in data. We demonstrate scDA is effective to determine cell types, revealing the overall variabilities between cells from eleven data sets. scDA also outperforms several state-of-the-art methods when inferring the labels of new samples. In particular, we found scDA less sensitive to drop-out events and capable to label a mass of cells within or across datasets after learning even from a small set of data. The scDA approach offers a new way to efficiently analyze scRNA-seq profiles of large size or from different batches. scDA was implemented and freely available at https://github.com/ZCCQQWork/scDA.
| S-EPMC8187165 | biostudies-literature
Project description:BackgroundSingle-cell RNA sequencing (scRNA-Seq) experiments are gaining ground to study the molecular processes that drive normal development as well as the onset of different pathologies. Finding an effective and efficient low-dimensional representation of the data is one of the most important steps in the downstream analysis of scRNA-Seq data, as it could provide a better identification of known or putatively novel cell-types. Another step that still poses a challenge is the integration of different scRNA-Seq datasets. Though standard computational pipelines to gain knowledge from scRNA-Seq data exist, a further improvement could be achieved by means of machine learning approaches.ResultsAutoencoders (AEs) have been effectively used to capture the non-linearities among gene interactions of scRNA-Seq data, so that the deployment of AE-based tools might represent the way forward in this context. We introduce here scAEspy, a unifying tool that embodies: (1) four of the most advanced AEs, (2) two novel AEs that we developed on purpose, (3) different loss functions. We show that scAEspy can be coupled with various batch-effect removal tools to integrate data by different scRNA-Seq platforms, in order to better identify the cell-types. We benchmarked scAEspy against the most used batch-effect removal tools, showing that our AE-based strategies outperform the existing solutions.ConclusionsscAEspy is a user-friendly tool that enables using the most recent and promising AEs to analyse scRNA-Seq data by only setting up two user-defined parameters. Thanks to its modularity, scAEspy can be easily extended to accommodate new AEs to further improve the downstream analysis of scRNA-Seq data. Considering the relevant results we achieved, scAEspy can be considered as a starting point to build a more comprehensive toolkit designed to integrate multi single-cell omics.
| S-EPMC8186186 | biostudies-literature
Project description:Single-cell RNA-sequencing (scRNA-seq) is a recent high-throughput genomic technology used to study the expression dynamics of genes at single-cell level. Analyzing the scRNA-seq data in presence of biological confounding factors including dropout events is a challenging task. Thus, this article presents a novel statistical approach for various analyses of the scRNA-seq Unique Molecular Identifier (UMI) counts data. The various analyses include modeling and fitting of observed UMI data, cell type detection, estimation of cell capture rates, estimation of gene specific model parameters, estimation of the sample mean and sample variance of the genes, etc. Besides, the developed approach is able to perform differential expression, and other downstream analyses that consider the molecular capture process in scRNA-seq data modeling. Here, the external spike-ins data can also be used in the approach for better results. The unique feature of the method is that it considers the biological process that leads to severe dropout events in modeling the observed UMI counts of genes. • The differential expression analysis of observed scRNA-seq UMI counts data is performed after adjustment for cell capture rates. • The statistical approach performs downstream differential zero inflation analysis, classification of influential genes, and selection of top marker genes. • Cell auxiliaries including cell clusters and other cell variables (e.g., cell cycle, cell phase) are used to remove unwanted variation to perform statistical tests reliably.
| S-EPMC8720898 | biostudies-literature
Project description:Comparative analysis of cell-cell communication at single-cell resolution
| PRJNA949652 | ENA
Project description:Single-cell RNA sequencing analysis of E14.5 mouse skin data
| PRJNA1075311 | ENA
Project description:The rapid advancement of single-cell technologies has shed new light on the complex mechanisms of cellular heterogeneity. However, compared to bulk RNA sequencing (RNA-seq), single-cell RNA-seq (scRNA-seq) suffers from higher noise and lower coverage, which brings new computational difficulties. Based on statistical independence, cell-specific network (CSN) is able to quantify the overall associations between genes for each cell, yet suffering from a problem of overestimation related to indirect effects. To overcome this problem, we propose the c-CSN method, which can construct the conditional cell-specific network (CCSN) for each cell. c-CSN method can measure the direct associations between genes by eliminating the indirect associations. c-CSN can be used for cell clustering and dimension reduction on a network basis of single cells. Intuitively, each CCSN can be viewed as the transformation from less "reliable" gene expression to more "reliable" gene-gene associations in a cell. Based on CCSN, we further design network flow entropy (NFE) to estimate the differentiation potency of a single cell. A number of scRNA-seq datasets were used to demonstrate the advantages of our approach. 1) One direct association network is generated for one cell. 2) Most existing scRNA-seq methods designed for gene expression matrices are also applicable to c-CSN-transformed degree matrices. 3) CCSN-based NFE helps resolving the direction of differentiation trajectories by quantifying the potency of each cell. c-CSN is publicly available at https://github.com/LinLi-0909/c-CSN.
| S-EPMC8602759 | biostudies-literature
Project description:Single Cell RNA / Single Nucleus RNA Sequencing Data of Human Pancreaitc Islet
| PRJNA900882 | ENA
Project description:Single-cell RNA sequencing data is characterized by a large number of zero counts, yet there is growing evidence that these zeros reflect biological variation rather than technical artifacts. We propose to use binarized expression profiles to identify the effects of biological variation in single-cell RNA sequencing data. Using 16 publicly available and simulated datasets, we show that a binarized representation of single-cell expression data accurately represents biological variation and reveals the relative abundance of transcripts more robustly than counts.
| S-EPMC8693570 | biostudies-literature