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Trajectory-based differential expression analysis for single-cell sequencing data

delete2020-03-05
delete343
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OA
AI
K
Koen Van den Berge
H
Hector Roux de Bézieux
K
Kelly Street
W
Wouter Saelens
R
Robrecht Cannoodt
Y
Yvan Saeys
S
Sandrine Dudoit *
L
Lieven Clement *
DOI:10.1038/s41467-020-14766-3delete
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Abstract

Abstract

En 中文
Trajectory inference has radically enhanced single-cell RNA-seq research by enabling the study of dynamic changes in gene expression. Downstream of trajectory inference, it is vital to discover genes that are (i) associated with the lineages in the trajectory, or (ii) differentially expressed between lineages, to illuminate the underlying biological processes. Current data analysis procedures, however, either fail to exploit the continuous resolution provided by trajectory inference, or fail to pinpoint the exact types of differential expression. We introduce tradeSeq, a powerful generalized additive model framework based on the negative binomial distribution that allows flexible inference of both within-lineage and between-lineage differential expression. By incorporating observation-level weights, the model additionally allows to account for zero inflation. We evaluate the method on simulated datasets and on real datasets from droplet-based and full-length protocols, and show that it yields biological insights through a clear interpretation of the data. Downstream of trajectory inference for cell lineages based on scRNA-seq data, differential expression analysis yields insight into biological processes. Here, Van den Berge et al. develop tradeSeq, a framework for the inference of within and between-lineage differential expression, based on negative binomial generalized additive models.

Journal

Nature Communications cover
Nature Communications
IF:
15.7
Papers:
9.4W
Citations:
91.2W

Organization

G
Ghent University
Scholars:
1.3K
Papers: 456
Citations: 0
University of California System cover
University of California System
Scholars:
37.7W
Papers: 33.8W
Citations: 6.6K
U
university of california berkeley
Scholars:
213
Papers: 115
Citations: 0
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Cited Papers

Cited Papers

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