Browse
Submit Data
Databases
API
Help

Dataset Information

47 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

IDEAS: individual level differential expression analysis for single-cell RNA-seq data.

ABSTRACT: We consider an increasingly popular study design where single-cell RNA-seq data are collected from multiple individuals and the question of interest is to find genes that are differentially expressed between two groups of individuals. Towards this end, we propose a statistical method named IDEAS (individual level differential expression analysis for scRNA-seq). For each gene, IDEAS summarizes its expression in each individual by a distribution and then assesses whether these individual-specific distributions are different between two groups of individuals. We apply IDEAS to assess gene expression differences of autism patients versus controls and COVID-19 patients with mild versus severe symptoms.

SUBMITTER: Zhang M

PROVIDER: S-EPMC8784862 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

IDEAS: individual level differential expression analysis for single-cell RNA-seq data.

Zhang Mengqi M Liu Si S Miao Zhen Z Han Fang F Gottardo Raphael R Sun Wei W

Genome biology 20220124 1

We consider an increasingly popular study design where single-cell RNA-seq data are collected from multiple individuals and the question of interest is to find genes that are differentially expressed between two groups of individuals. Towards this end, we propose a statistical method named IDEAS (individual level differential expression analysis for scRNA-seq). For each gene, IDEAS summarizes its expression in each individual by a distribution and then assesses whether these individual-specific ...[more]

PMID: 35073995

Similar Datasets

Differential expression of single-cell RNA-seq data using Tweedie models.

Project description:The performance of computational methods and software to identify differentially expressed features in single-cell RNA-sequencing (scRNA-seq) has been shown to be influenced by several factors, including the choice of the normalization method used and the choice of the experimental platform (or library preparation protocol) to profile gene expression in individual cells. Currently, it is up to the practitioner to choose the most appropriate differential expression (DE) method out of over 100 DE tools available to date, each relying on their own assumptions to model scRNA-seq expression features. To model the technological variability in cross-platform scRNA-seq data, here we propose to use Tweedie generalized linear models that can flexibly capture a large dynamic range of observed scRNA-seq expression profiles across experimental platforms induced by platform- and gene-specific statistical properties such as heavy tails, sparsity, and gene expression distributions. We also propose a zero-inflated Tweedie model that allows zero probability mass to exceed a traditional Tweedie distribution to model zero-inflated scRNA-seq data with excessive zero counts. Using both synthetic and published plate- and droplet-based scRNA-seq datasets, we perform a systematic benchmark evaluation of more than 10 representative DE methods and demonstrate that our method (Tweedieverse) outperforms the state-of-the-art DE approaches across experimental platforms in terms of statistical power and false discovery rate control. Our open-source software (R/Bioconductor package) is available at https://github.com/himelmallick/Tweedieverse.

| S-EPMC9288986 | biostudies-literature

DECENT: differential expression with capture efficiency adjustmeNT for single-cell RNA-seq data.

Project description:MotivationDropout is a common phenomenon in single-cell RNA-seq (scRNA-seq) data, and when left unaddressed it affects the validity of the statistical analyses. Despite this, few current methods for differential expression (DE) analysis of scRNA-seq data explicitly model the process that gives rise to the dropout events. We develop DECENT, a method for DE analysis of scRNA-seq data that explicitly and accurately models the molecule capture process in scRNA-seq experiments.ResultsWe show that DECENT demonstrates improved DE performance over existing DE methods that do not explicitly model dropout. This improvement is consistently observed across several public scRNA-seq datasets generated using different technological platforms. The gain in improvement is especially large when the capture process is overdispersed. DECENT maintains type I error well while achieving better sensitivity. Its performance without spike-ins is almost as good as when spike-ins are used to calibrate the capture model.Availability and implementationThe method is implemented as a publicly available R package available from https://github.com/cz-ye/DECENT.Supplementary informationSupplementary data are available at Bioinformatics online.

| S-EPMC6954660 | biostudies-literature

DTWscore: differential expression and cell clustering analysis for time-series single-cell RNA-seq data.

Project description:BackgroundThe development of single-cell RNA sequencing has enabled profound discoveries in biology, ranging from the dissection of the composition of complex tissues to the identification of novel cell types and dynamics in some specialized cellular environments. However, the large-scale generation of single-cell RNA-seq (scRNA-seq) data collected at multiple time points remains a challenge to effective measurement gene expression patterns in transcriptome analysis.ResultsWe present an algorithm based on the Dynamic Time Warping score (DTWscore) combined with time-series data, that enables the detection of gene expression changes across scRNA-seq samples and recovery of potential cell types from complex mixtures of multiple cell types.ConclusionsThe DTWscore successfully classify cells of different types with the most highly variable genes from time-series scRNA-seq data. The study was confined to methods that are implemented and available within the R framework. Sample datasets and R packages are available at https://github.com/xiaoxiaoxier/DTWscore .

| S-EPMC5442705 | biostudies-literature

Overcoming confounding plate effects in differential expression analyses of single-cell RNA-seq data.

Project description:An increasing number of studies are using single-cell RNA-sequencing (scRNA-seq) to characterize the gene expression profiles of individual cells. One common analysis applied to scRNA-seq data involves detecting differentially expressed (DE) genes between cells in different biological groups. However, many experiments are designed such that the cells to be compared are processed in separate plates or chips, meaning that the groupings are confounded with systematic plate effects. This confounding aspect is frequently ignored in DE analyses of scRNA-seq data. In this article, we demonstrate that failing to consider plate effects in the statistical model results in loss of type I error control. A solution is proposed whereby counts are summed from all cells in each plate and the count sums for all plates are used in the DE analysis. This restores type I error control in the presence of plate effects without compromising detection power in simulated data. Summation is also robust to varying numbers and library sizes of cells on each plate. Similar results are observed in DE analyses of real data where the use of count sums instead of single-cell counts improves specificity and the ranking of relevant genes. This suggests that summation can assist in maintaining statistical rigour in DE analyses of scRNA-seq data with plate effects.

| S-EPMC5862359 | biostudies-literature

Differential expression analysis of RNA-seq data at single-base resolution.

Project description:RNA-sequencing (RNA-seq) is a flexible technology for measuring genome-wide expression that is rapidly replacing microarrays as costs become comparable. Current differential expression analysis methods for RNA-seq data fall into two broad classes: (1) methods that quantify expression within the boundaries of genes previously published in databases and (2) methods that attempt to reconstruct full length RNA transcripts. The first class cannot discover differential expression outside of previously known genes. While the second approach does possess discovery capabilities, statistical analysis of differential expression is complicated by the ambiguity and variability incurred while assembling transcripts and estimating their abundances. Here, we propose a novel method that first identifies differentially expressed regions (DERs) of interest by assessing differential expression at each base of the genome. The method then segments the genome into regions comprised of bases showing similar differential expression signal, and then assigns a measure of statistical significance to each region. Optionally, DERs can be annotated using a reference database of genomic features. We compare our approach with leading competitors from both current classes of differential expression methods and highlight the strengths and weaknesses of each. A software implementation of our method is available on github (https://github.com/alyssafrazee/derfinder).

| S-EPMC4059460 | biostudies-literature

Two-phase differential expression analysis for single cell RNA-seq.

Project description:Motivation:Single-cell RNA-sequencing (scRNA-seq) has brought the study of the transcriptome to higher resolution and makes it possible for scientists to provide answers with more clarity to the question of 'differential expression'. However, most computational methods still stick with the old mentality of viewing differential expression as a simple 'up or down' phenomenon. We advocate that we should fully embrace the features of single cell data, which allows us to observe binary (from Off to On) as well as continuous (the amount of expression) regulations. Results:We develop a method, termed SC2P, that first identifies the phase of expression a gene is in, by taking into account of both cell- and gene-specific contexts, in a model-based and data-driven fashion. We then identify two forms of transcription regulation: phase transition, and magnitude tuning. We demonstrate that compared with existing methods, SC2P provides substantial improvement in sensitivity without sacrificing the control of false discovery, as well as better robustness. Furthermore, the analysis provides better interpretation of the nature of regulation types in different genes. Availability and implementation:SC2P is implemented as an open source R package publicly available at https://github.com/haowulab/SC2P. Supplementary information:Supplementary data are available at Bioinformatics online.

| S-EPMC6157076 | biostudies-literature

SwarnSeq: An improved statistical approach for differential expression analysis of single-cell RNA-seq data.

Project description:Single-cell RNA sequencing (scRNA-seq) is a powerful technology that is capable of generating gene expression data at the resolution of individual cell. The scRNA-seq data is characterized by the presence of dropout events, which severely bias the results if they remain unaddressed. There are limited Differential Expression (DE) approaches which consider the biological processes, which lead to dropout events, in the modeling process. So, we develop, SwarnSeq, an improved method for DE, and other downstream analysis that considers the molecular capture process in scRNA-seq data modeling. The performance of the proposed method is benchmarked with 11 existing methods on 10 different real scRNA-seq datasets under three comparison settings. We demonstrate that SwarnSeq method has improved performance over the 11 existing methods. This improvement is consistently observed across several public scRNA-seq datasets generated using different scRNA-seq protocols. The external spike-ins data can be used in the SwarnSeq method to enhance its performance. AVAILABILITY AND IMPLEMENTATION: The method is implemented as a publicly available R package available at https://github.com/sam-uofl/SwarnSeq.

| S-EPMC10150572 | biostudies-literature

Differential Expression Analysis of Single-Cell RNA-Seq Data: Current Statistical Approaches and Outstanding Challenges.

Project description:With the advent of single-cell RNA-sequencing (scRNA-seq), it is possible to measure the expression dynamics of genes at the single-cell level. Through scRNA-seq, a huge amount of expression data for several thousand(s) of genes over million(s) of cells are generated in a single experiment. Differential expression analysis is the primary downstream analysis of such data to identify gene markers for cell type detection and also provide inputs to other secondary analyses. Many statistical approaches for differential expression analysis have been reported in the literature. Therefore, we critically discuss the underlying statistical principles of the approaches and distinctly divide them into six major classes, i.e., generalized linear, generalized additive, Hurdle, mixture models, two-class parametric, and non-parametric approaches. We also succinctly discuss the limitations that are specific to each class of approaches, and how they are addressed by other subsequent classes of approach. A number of challenges are identified in this study that must be addressed to develop the next class of innovative approaches. Furthermore, we also emphasize the methodological challenges involved in differential expression analysis of scRNA-seq data that researchers must address to draw maximum benefit from this recent single-cell technology. This study will serve as a guide to genome researchers and experimental biologists to objectively select options for their analysis.

| S-EPMC9315519 | biostudies-literature

Differential detection workflows for multi-sample single-cell RNA-seq data.

Project description:In single-cell transcriptomics, differential gene expression (DE) analyses typically focus on testing differences in the average expression of genes between cell types or conditions of interest. Single-cell transcriptomics, however, also has the promise to prioritise genes for which the expression differ in other aspects of the distribution. Here we develop a workflow for assessing differential detection (DD), which tests for differences in the average fraction of samples or cells in which a gene is detected. After benchmarking eight different DD data analysis strategies, we provide a unified workflow for jointly assessing DE and DD. Using simulations and two case studies, we show that DE and DD analysis provide complementary information, both in terms of the individual genes they report and in the functional interpretation of those genes.

| S-EPMC10769270 | biostudies-literature

Corrigendum: Differential expression analysis of RNA-seq data at single-base resolution

Project description: Not available

| S-EPMC4059467 | biostudies-literature