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

Nature Communications
Koen Van den BergeLieven Clement

Abstract

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.

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Citations

Jul 18, 2020·Nature Communications·Maximilian StrunzHerbert B Schiller
Jul 15, 2020·Nature Methods·Shila GhazanfarJean Yee Hwa Yang
Nov 12, 2020·Frontiers in Psychiatry·Jeffrey J KimJames N Kirby
Jan 21, 2021·Bioinformatics·Scott Van BurenMichael I Love
Jan 16, 2021·Proceedings of the National Academy of Sciences of the United States of America·Daniel C EllwangerMarco Colonna
Mar 4, 2021·Proceedings of the National Academy of Sciences of the United States of America·Haikel N BogaleDavid Serre
Mar 17, 2021·Journal of the American Society of Nephrology : JASN·Michael S BalzerKatalin Susztak
Mar 9, 2021·Parasitology·Emma M BriggsThomas D Otto
May 18, 2021·Frontiers in Cell and Developmental Biology·Wojciech J SzlachcicMalgorzata Borowiak
May 23, 2021·Communications Biology·Yasser Iturria-MedinaLazaro Sanchez-Rodriguez
May 29, 2021·Nature Structural & Molecular Biology·Ane IturbideMaria-Elena Torres-Padilla
Jul 17, 2021·Nature Communications·Michael LattkeFrancois Guillemot
Jul 27, 2021·Molecular Systems Biology·Sergio TrianaTheodore Alexandrov
Jul 3, 2021·Bioinformatics·Nuha BinTayyashMagnus Rattray

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Datasets Mentioned

BETA
GSE95601
GSE128889

Methods Mentioned

BETA
scRNA-seq
RNA-seq
GAM
PCA
Smart-seq
in

Software Mentioned

tradeSeq
Bioconductor R package iCOBRA
patternTest
clusterExperiment
mgcv
Monocle
dynverse
dyntoy
ImpulseDE2
dyngen

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