Dissection and integration of bursty transcriptional dynamics for complex systems.
In: Proceedings of the National Academy of Sciences of the United States of America, Jg. 121 (2024-04-30), Heft 18, S. e2306901121
academicJournal
Zugriff:
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.
Titel: |
Dissection and integration of bursty transcriptional dynamics for complex systems.
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Autor/in / Beteiligte Person: | Gao, CF ; Vaikuntanathan, S ; Riesenfeld, SJ |
Zeitschrift: | Proceedings of the National Academy of Sciences of the United States of America, Jg. 121 (2024-04-30), Heft 18, S. e2306901121 |
Veröffentlichung: | Washington, DC : National Academy of Sciences, 2024 |
Medientyp: | academicJournal |
ISSN: | 1091-6490 (electronic) |
DOI: | 10.1073/pnas.2306901121 |
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