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Deep generative modeling of transcriptional dynamics for RNA velocity analysis in single cells.
Nat. Methods 21, 50-59 (2024)
RNA velocity has been rapidly adopted to guide interpretation of transcriptional dynamics in snapshot single-cell data; however, current approaches for estimating RNA velocity lack effective strategies for quantifying uncertainty and determining the overall applicability to the system of interest. Here, we present veloVI (velocity variational inference), a deep generative modeling framework for estimating RNA velocity. veloVI learns a gene-specific dynamical model of RNA metabolism and provides a transcriptome-wide quantification of velocity uncertainty. We show that veloVI compares favorably to previous approaches with respect to goodness of fit, consistency across transcriptionally similar cells and stability across preprocessing pipelines for quantifying RNA abundance. Further, we demonstrate that veloVI’s posterior velocity uncertainty can be used to assess whether velocity analysis is appropriate for a given dataset. Finally, we highlight veloVI as a flexible framework for modeling transcriptional dynamics by adapting the underlying dynamical model to use time-dependent transcription rates.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
ISSN (print) / ISBN
1548-7091
e-ISSN
1548-7105
Zeitschrift
Nature Methods
Quellenangaben
Band: 21,
Heft: 1,
Seiten: 50-59
Verlag
Nature Publishing Group
Verlagsort
New York, NY
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Computational Biology (ICB)