Observation weights unlock bulk RNA-seq tools for zero inflation and single-cell applications

Abstract Dropout events in single-cell RNA sequencing (scRNA-seq) cause many transcripts to go undetected and induce an excess of zero read counts, leading to power issues in differential expression (DE) analysis. This has triggered the development of bespoke scRNA-seq DE methods to cope with zero i...

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Main Authors: Koen Van den Berge, Fanny Perraudeau, Charlotte Soneson, Michael I. Love, Davide Risso, Jean-Philippe Vert, Mark D. Robinson, Sandrine Dudoit, Lieven Clement
Format: Article
Language:English
Published: BMC 2018-02-01
Series:Genome Biology
Subjects:
Online Access:http://link.springer.com/article/10.1186/s13059-018-1406-4
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author Koen Van den Berge
Fanny Perraudeau
Charlotte Soneson
Michael I. Love
Davide Risso
Jean-Philippe Vert
Mark D. Robinson
Sandrine Dudoit
Lieven Clement
author_facet Koen Van den Berge
Fanny Perraudeau
Charlotte Soneson
Michael I. Love
Davide Risso
Jean-Philippe Vert
Mark D. Robinson
Sandrine Dudoit
Lieven Clement
author_sort Koen Van den Berge
collection DOAJ
description Abstract Dropout events in single-cell RNA sequencing (scRNA-seq) cause many transcripts to go undetected and induce an excess of zero read counts, leading to power issues in differential expression (DE) analysis. This has triggered the development of bespoke scRNA-seq DE methods to cope with zero inflation. Recent evaluations, however, have shown that dedicated scRNA-seq tools provide no advantage compared to traditional bulk RNA-seq tools. We introduce a weighting strategy, based on a zero-inflated negative binomial model, that identifies excess zero counts and generates gene- and cell-specific weights to unlock bulk RNA-seq DE pipelines for zero-inflated data, boosting performance for scRNA-seq.
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spelling doaj.art-1fb890a1e7054cc1bb3da7acb3f98b6c2022-12-22T00:10:55ZengBMCGenome Biology1474-760X2018-02-0119111710.1186/s13059-018-1406-4Observation weights unlock bulk RNA-seq tools for zero inflation and single-cell applicationsKoen Van den Berge0Fanny Perraudeau1Charlotte Soneson2Michael I. Love3Davide Risso4Jean-Philippe Vert5Mark D. Robinson6Sandrine Dudoit7Lieven Clement8Department of Applied Mathematics, Computer Science and Statistics, Ghent UniversityDivision of Biostatistics, School of Public Health, University of CaliforniaInstitute of Molecular Life Sciences, University of ZurichDepartment of Biostatistics and Genetics, The University of North Carolina at Chapel HillDivision of Biostatistics and Epidemiology, Department of Healthcare Policy and Research, Weill Cornell MedicineMINES ParisTech, PSL Research University, CBIO-Centre for Computational BiologyInstitute of Molecular Life Sciences, University of ZurichDivision of Biostatistics, School of Public Health, University of CaliforniaDepartment of Applied Mathematics, Computer Science and Statistics, Ghent UniversityAbstract Dropout events in single-cell RNA sequencing (scRNA-seq) cause many transcripts to go undetected and induce an excess of zero read counts, leading to power issues in differential expression (DE) analysis. This has triggered the development of bespoke scRNA-seq DE methods to cope with zero inflation. Recent evaluations, however, have shown that dedicated scRNA-seq tools provide no advantage compared to traditional bulk RNA-seq tools. We introduce a weighting strategy, based on a zero-inflated negative binomial model, that identifies excess zero counts and generates gene- and cell-specific weights to unlock bulk RNA-seq DE pipelines for zero-inflated data, boosting performance for scRNA-seq.http://link.springer.com/article/10.1186/s13059-018-1406-4Single-cell RNA sequencingDifferential expressionZero-inflated negative binomialWeights
spellingShingle Koen Van den Berge
Fanny Perraudeau
Charlotte Soneson
Michael I. Love
Davide Risso
Jean-Philippe Vert
Mark D. Robinson
Sandrine Dudoit
Lieven Clement
Observation weights unlock bulk RNA-seq tools for zero inflation and single-cell applications
Genome Biology
Single-cell RNA sequencing
Differential expression
Zero-inflated negative binomial
Weights
title Observation weights unlock bulk RNA-seq tools for zero inflation and single-cell applications
title_full Observation weights unlock bulk RNA-seq tools for zero inflation and single-cell applications
title_fullStr Observation weights unlock bulk RNA-seq tools for zero inflation and single-cell applications
title_full_unstemmed Observation weights unlock bulk RNA-seq tools for zero inflation and single-cell applications
title_short Observation weights unlock bulk RNA-seq tools for zero inflation and single-cell applications
title_sort observation weights unlock bulk rna seq tools for zero inflation and single cell applications
topic Single-cell RNA sequencing
Differential expression
Zero-inflated negative binomial
Weights
url http://link.springer.com/article/10.1186/s13059-018-1406-4
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