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Statistical methods for analysis of single-cell RNA-sequencing data.

作者信息

Das Samarendra, Rai Shesh N

机构信息

Division of Statistical Genetics, ICAR-Indian Agricultural Statistics Research Institute, PUSA, New Delhi 110012, India.

Biostatistics and Bioinformatics Facility, JG Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA.

出版信息

MethodsX. 2021 Nov 17;8:101580. doi: 10.1016/j.mex.2021.101580. eCollection 2021.


DOI:10.1016/j.mex.2021.101580
PMID:35004214
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8720898/
Abstract

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, . 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 (, cell cycle, cell phase) are used to remove unwanted variation to perform statistical tests reliably.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3ab/8720898/76ecd9fa98fa/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3ab/8720898/d66ca42fd9e1/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3ab/8720898/c622659f0711/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3ab/8720898/289e0c24a137/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3ab/8720898/6f8a7d26d06d/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3ab/8720898/99cad5fdccf1/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3ab/8720898/bd09b2734145/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3ab/8720898/76ecd9fa98fa/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3ab/8720898/d66ca42fd9e1/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3ab/8720898/c622659f0711/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3ab/8720898/289e0c24a137/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3ab/8720898/6f8a7d26d06d/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3ab/8720898/99cad5fdccf1/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3ab/8720898/bd09b2734145/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3ab/8720898/76ecd9fa98fa/gr6.jpg

相似文献

[1]
Statistical methods for analysis of single-cell RNA-sequencing data.

MethodsX. 2021-11-17

[2]
SwarnSeq: An improved statistical approach for differential expression analysis of single-cell RNA-seq data.

Genomics. 2021-5

[3]
ZERO-INFLATED QUANTILE RANK-SCORE BASED TEST (ZIQRANK) WITH APPLICATION TO SCRNA-SEQ DIFFERENTIAL GENE EXPRESSION ANALYSIS.

Ann Appl Stat. 2021-12

[4]
UMI-count modeling and differential expression analysis for single-cell RNA sequencing.

Genome Biol. 2018-5-31

[5]
Modeling dynamic correlation in zero-inflated bivariate count data with applications to single-cell RNA sequencing data.

Biometrics. 2022-6

[6]
Analytic Pearson residuals for normalization of single-cell RNA-seq UMI data.

Genome Biol. 2021-9-6

[7]
Detecting differential alternative splicing events in scRNA-seq with or without Unique Molecular Identifiers.

PLoS Comput Biol. 2020-6-5

[8]
Gene length and detection bias in single cell RNA sequencing protocols.

F1000Res. 2017-4-28

[9]
Observation weights unlock bulk RNA-seq tools for zero inflation and single-cell applications.

Genome Biol. 2018-2-26

[10]
Bayesian gamma-negative binomial modeling of single-cell RNA sequencing data.

BMC Genomics. 2020-9-9

引用本文的文献

[1]
Anti-aging Effects of Alu Antisense RNA on Human Fibroblast Senescence Through the MEK-ERK Pathway Mediated by KIF15.

Curr Med Sci. 2023-2

[2]
Differential Expression Analysis of Single-Cell RNA-Seq Data: Current Statistical Approaches and Outstanding Challenges.

Entropy (Basel). 2022-7-18

[3]
A Comprehensive Survey of Statistical Approaches for Differential Expression Analysis in Single-Cell RNA Sequencing Studies.

Genes (Basel). 2021-12-2

本文引用的文献

[1]
SwarnSeq: An improved statistical approach for differential expression analysis of single-cell RNA-seq data.

Genomics. 2021-5

[2]
DECENT: differential expression with capture efficiency adjustmeNT for single-cell RNA-seq data.

Bioinformatics. 2019-12-15

[3]
DEsingle for detecting three types of differential expression in single-cell RNA-seq data.

Bioinformatics. 2018-9-15

[4]
Observation weights unlock bulk RNA-seq tools for zero inflation and single-cell applications.

Genome Biol. 2018-2-26

[5]
Comparative Analysis of Single-Cell RNA Sequencing Methods.

Mol Cell. 2017-2-16

[6]
Batch effects and the effective design of single-cell gene expression studies.

Sci Rep. 2017-1-3

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