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Gayoso, A.* ; Weiler, P. ; Lotfollahi, M. ; Klein, D. ; Hong, J.* ; Streets, A.* ; Theis, F.J. ; Yosef, N.*

Deep generative modeling of transcriptional dynamics for RNA velocity analysis in single cells.

Nat. Methods 21, 50-59 (2024)
DOI PMC
Creative Commons Lizenzvertrag
Open Access Green as soon as Postprint is submitted to ZB.
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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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
ISSN (print) / ISBN 1548-7091
e-ISSN 1548-7105
Journal Nature Methods
Quellenangaben Volume: 21, Issue: 1, Pages: 50-59 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place New York, NY
Non-patent literature Publications
Reviewing status Peer reviewed