Dissection and integration of bursty transcriptional dynamics for complex systems.

Autor:	Gao CF; Department of Chemistry, University of Chicago, Chicago, IL 60637., Vaikuntanathan S; Department of Chemistry, University of Chicago, Chicago, IL 60637.; Institute for Biophysical Dynamics, University of Chicago, Chicago, IL 60637., Riesenfeld SJ; Institute for Biophysical Dynamics, University of Chicago, Chicago, IL 60637.; Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL 60637.; Department of Medicine, University of Chicago, Chicago, IL 60637.; Committee on Immunology, Biological Sciences Division, University of Chicago, Chicago, IL 60637.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2024 Apr 30; Vol. 121 (18), pp. e2306901121. Date of Electronic Publication: 2024 Apr 26.
DOI:	10.1073/pnas.2306901121
Abstrakt:	RNA velocity estimation is a potentially powerful tool to reveal the directionality of transcriptional changes in single-cell RNA-sequencing data, but it lacks accuracy, absent advanced metabolic labeling techniques. We developed an approach, TopicVelo , that disentangles simultaneous, yet distinct, dynamics by using a probabilistic topic model, a highly interpretable form of latent space factorization, to infer cells and genes associated with individual processes, thereby capturing cellular pluripotency or multifaceted functionality. Focusing on process-associated cells and genes enables accurate estimation of process-specific velocities via a master equation for a transcriptional burst model accounting for intrinsic stochasticity. The method obtains a global transition matrix by leveraging cell topic weights to integrate process-specific signals. In challenging systems, this method accurately recovers complex transitions and terminal states, while our use of first-passage time analysis provides insights into transient transitions. These results expand the limits of RNA velocity, empowering future studies of cell fate and functional responses. Competing Interests: Competing interests statement:The authors disclose the following patent filing: “Computational Models to Analyze RNA Velocity”; Case number: UCHI 22-T-208-001; Date filed: 17 January 2023.
Databáze:	MEDLINE
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