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MAST: a flexible statistical framework for assessing transcriptional changes and characterizing heterogeneity in single-cell RNA sequencing data

Single-cell transcriptomics reveals gene expression heterogeneity but suffers from stochastic dropout and characteristic bimodal expression distributions in which expression is either strongly non-zero or non-detectable. We propose a two-part, generalized linear model for such bimodal data that para...

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Autores principales: Finak, Greg, McDavid, Andrew, Yajima, Masanao, Deng, Jingyuan, Gersuk, Vivian, Shalek, Alex K., Slichter, Chloe K., Miller, Hannah W., McElrath, M. Juliana, Prlic, Martin, Linsley, Peter S., Gottardo, Raphael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4676162/
https://www.ncbi.nlm.nih.gov/pubmed/26653891
http://dx.doi.org/10.1186/s13059-015-0844-5
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author Finak, Greg
McDavid, Andrew
Yajima, Masanao
Deng, Jingyuan
Gersuk, Vivian
Shalek, Alex K.
Slichter, Chloe K.
Miller, Hannah W.
McElrath, M. Juliana
Prlic, Martin
Linsley, Peter S.
Gottardo, Raphael
author_facet Finak, Greg
McDavid, Andrew
Yajima, Masanao
Deng, Jingyuan
Gersuk, Vivian
Shalek, Alex K.
Slichter, Chloe K.
Miller, Hannah W.
McElrath, M. Juliana
Prlic, Martin
Linsley, Peter S.
Gottardo, Raphael
author_sort Finak, Greg
collection PubMed
description Single-cell transcriptomics reveals gene expression heterogeneity but suffers from stochastic dropout and characteristic bimodal expression distributions in which expression is either strongly non-zero or non-detectable. We propose a two-part, generalized linear model for such bimodal data that parameterizes both of these features. We argue that the cellular detection rate, the fraction of genes expressed in a cell, should be adjusted for as a source of nuisance variation. Our model provides gene set enrichment analysis tailored to single-cell data. It provides insights into how networks of co-expressed genes evolve across an experimental treatment. MAST is available at https://github.com/RGLab/MAST. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-015-0844-5) contains supplementary material, which is available to authorized users.
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spelling pubmed-46761622015-12-12 MAST: a flexible statistical framework for assessing transcriptional changes and characterizing heterogeneity in single-cell RNA sequencing data Finak, Greg McDavid, Andrew Yajima, Masanao Deng, Jingyuan Gersuk, Vivian Shalek, Alex K. Slichter, Chloe K. Miller, Hannah W. McElrath, M. Juliana Prlic, Martin Linsley, Peter S. Gottardo, Raphael Genome Biol Method Single-cell transcriptomics reveals gene expression heterogeneity but suffers from stochastic dropout and characteristic bimodal expression distributions in which expression is either strongly non-zero or non-detectable. We propose a two-part, generalized linear model for such bimodal data that parameterizes both of these features. We argue that the cellular detection rate, the fraction of genes expressed in a cell, should be adjusted for as a source of nuisance variation. Our model provides gene set enrichment analysis tailored to single-cell data. It provides insights into how networks of co-expressed genes evolve across an experimental treatment. MAST is available at https://github.com/RGLab/MAST. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-015-0844-5) contains supplementary material, which is available to authorized users. BioMed Central 2015-12-10 2015 /pmc/articles/PMC4676162/ /pubmed/26653891 http://dx.doi.org/10.1186/s13059-015-0844-5 Text en © Finak et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Method
Finak, Greg
McDavid, Andrew
Yajima, Masanao
Deng, Jingyuan
Gersuk, Vivian
Shalek, Alex K.
Slichter, Chloe K.
Miller, Hannah W.
McElrath, M. Juliana
Prlic, Martin
Linsley, Peter S.
Gottardo, Raphael
MAST: a flexible statistical framework for assessing transcriptional changes and characterizing heterogeneity in single-cell RNA sequencing data
title MAST: a flexible statistical framework for assessing transcriptional changes and characterizing heterogeneity in single-cell RNA sequencing data
title_full MAST: a flexible statistical framework for assessing transcriptional changes and characterizing heterogeneity in single-cell RNA sequencing data
title_fullStr MAST: a flexible statistical framework for assessing transcriptional changes and characterizing heterogeneity in single-cell RNA sequencing data
title_full_unstemmed MAST: a flexible statistical framework for assessing transcriptional changes and characterizing heterogeneity in single-cell RNA sequencing data
title_short MAST: a flexible statistical framework for assessing transcriptional changes and characterizing heterogeneity in single-cell RNA sequencing data
title_sort mast: a flexible statistical framework for assessing transcriptional changes and characterizing heterogeneity in single-cell rna sequencing data
topic Method
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4676162/
https://www.ncbi.nlm.nih.gov/pubmed/26653891
http://dx.doi.org/10.1186/s13059-015-0844-5
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