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

TitleObservation weights unlock bulk RNA-seq tools for zero inflation and single-cell applications.
Publication TypeJournal Article
Year of Publication2018
AuthorsVan den Berge, Koen, Fanny Perraudeau, Charlotte Soneson, Michael I. Love, Davide Risso, Jean-Philippe Vert, Mark D. Robinson, Sandrine Dudoit, and Lieven Clement
JournalGenome Biol
Volume19
Issue1
Pagination24
Date Published2018 02 26
ISSN1474-760X
KeywordsGene Expression Profiling, Sequence Analysis, RNA, Single-Cell Analysis, Software
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.

DOI10.1186/s13059-018-1406-4
Alternate JournalGenome Biol
Original PublicationObservation weights unlock bulk RNA-seq tools for zero inflation and single-cell applications.
PubMed ID29478411
PubMed Central IDPMC6251479
Grant ListABS4NGS ANR-11-BINF-0001 / / Agence Nationale de la Recherche / International
1S 418 16N / / Fonds Wetenschappelijk Onderzoek / International
U01 MH105979 / MH / NIMH NIH HHS / United States
P7/06 / / IAP StUDyS grant / International
280032 / ERC_ / European Research Council / International
U01 MH105979 / NH / NIH HHS / United States
P01 CA142538 / CA / NCI NIH HHS / United States
CA142538-08 / NH / NIH HHS / United States
FK-16-107 / / Forschungskredit / International
ERC-SMAC-290032 / ERC_ / European Research Council / International
Project: