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

أوزان المراقبة لفتح أدوات تسلسل الحمض النووي الريبي بالجملة للتضخم الصفري والتطبيقات أحادية الخلية
Authors: Davide Risso; Mark D. Robinson; Mark D. Robinson; Fanny Perraudeau; Sandrine Dudoit; Charlotte Soneson; Charlotte Soneson; +4 Authors

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

Abstract

AbstractDropout events in single-cell transcriptome 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 (ZINB) 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.

Keywords

Cancer Research, sequence variation, Method, QH426-470, Gene, 1307 Cell Biology, Single-cell RNA sequencing, Computational biology, MAMMALIAN-CELLS, Droplet-based Sequencing, HETEROGENEITY, RNA-Seq, Biology (General), GENE-EXPRESSION, Lineage Tracking, Statistics, Life Sciences, Zero-inflated negative binomial, Biological Sciences, Comprehensive Integration of Single-Cell Transcriptomic Data, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 10124 Institute of Molecular Life Sciences, FOS: Philosophy, ethics and religion, sequence alignment, Single-Cell Analysis, Sequence Analysis, PACKAGE, 330, SEQUENCING DATA, Bioinformatics, QH301-705.5, Bioinformatics and Computational Biology, Differential expression; Single-cell RNA sequencing; Weights; Zero-inflated negative binomial;, Differential expression, 1311 Genetics, Weights, Information and Computing Sciences, Biochemistry, Genetics and Molecular Biology, FOS: Mathematics, Genetics, TRANSCRIPTOMICS, RNA Sequencing Data Analysis, Molecular Biology, Biology, Sequence Analysis, RNA, Gene Expression Profiling, Zero (linguistics), Biology and Life Sciences, Linguistics, Computer science, Genomic Landscape of Cancer and Mutational Signatures, Philosophy, 1105 Ecology, Evolution, Behavior and Systematics, DIFFERENTIAL EXPRESSION ANALYSIS, FOS: Biological sciences, FOS: Languages and literature, Poisson distribution, 570 Life sciences; biology, RNA, Negative binomial distribution, Gene expression, Transcriptome, Environmental Sciences, Software, Mathematics

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
166
Top 1%
Top 10%
Top 1%
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gold