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PseudotimeDE: inference of differential gene expression along cell pseudotime with well-calibrated p-values from single-cell RNA sequencing data

To investigate molecular mechanisms underlying cell state changes, a crucial analysis is to identify differentially expressed (DE) genes along the pseudotime inferred from single-cell RNA-sequencing data. However, existing methods do not account for pseudotime inference uncertainty, and they have ei...

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Autores principales: Song, Dongyuan, Li, Jingyi Jessica
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082818/
https://www.ncbi.nlm.nih.gov/pubmed/33926517
http://dx.doi.org/10.1186/s13059-021-02341-y
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author Song, Dongyuan
Li, Jingyi Jessica
author_facet Song, Dongyuan
Li, Jingyi Jessica
author_sort Song, Dongyuan
collection PubMed
description To investigate molecular mechanisms underlying cell state changes, a crucial analysis is to identify differentially expressed (DE) genes along the pseudotime inferred from single-cell RNA-sequencing data. However, existing methods do not account for pseudotime inference uncertainty, and they have either ill-posed p-values or restrictive models. Here we propose PseudotimeDE, a DE gene identification method that adapts to various pseudotime inference methods, accounts for pseudotime inference uncertainty, and outputs well-calibrated p-values. Comprehensive simulations and real-data applications verify that PseudotimeDE outperforms existing methods in false discovery rate control and power. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at (10.1186/s13059-021-02341-y).
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spelling pubmed-80828182021-04-29 PseudotimeDE: inference of differential gene expression along cell pseudotime with well-calibrated p-values from single-cell RNA sequencing data Song, Dongyuan Li, Jingyi Jessica Genome Biol Method To investigate molecular mechanisms underlying cell state changes, a crucial analysis is to identify differentially expressed (DE) genes along the pseudotime inferred from single-cell RNA-sequencing data. However, existing methods do not account for pseudotime inference uncertainty, and they have either ill-posed p-values or restrictive models. Here we propose PseudotimeDE, a DE gene identification method that adapts to various pseudotime inference methods, accounts for pseudotime inference uncertainty, and outputs well-calibrated p-values. Comprehensive simulations and real-data applications verify that PseudotimeDE outperforms existing methods in false discovery rate control and power. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at (10.1186/s13059-021-02341-y). BioMed Central 2021-04-29 /pmc/articles/PMC8082818/ /pubmed/33926517 http://dx.doi.org/10.1186/s13059-021-02341-y Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Method
Song, Dongyuan
Li, Jingyi Jessica
PseudotimeDE: inference of differential gene expression along cell pseudotime with well-calibrated p-values from single-cell RNA sequencing data
title PseudotimeDE: inference of differential gene expression along cell pseudotime with well-calibrated p-values from single-cell RNA sequencing data
title_full PseudotimeDE: inference of differential gene expression along cell pseudotime with well-calibrated p-values from single-cell RNA sequencing data
title_fullStr PseudotimeDE: inference of differential gene expression along cell pseudotime with well-calibrated p-values from single-cell RNA sequencing data
title_full_unstemmed PseudotimeDE: inference of differential gene expression along cell pseudotime with well-calibrated p-values from single-cell RNA sequencing data
title_short PseudotimeDE: inference of differential gene expression along cell pseudotime with well-calibrated p-values from single-cell RNA sequencing data
title_sort pseudotimede: inference of differential gene expression along cell pseudotime with well-calibrated p-values from single-cell rna sequencing data
topic Method
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082818/
https://www.ncbi.nlm.nih.gov/pubmed/33926517
http://dx.doi.org/10.1186/s13059-021-02341-y
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