1. Dissection and integration of bursty transcriptional dynamics for complex systems.
- Author
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Gaoa, Cheng Frank, Vaikuntanathana, Suriyanarayanan, and Riesenfel, Samantha J.
- Subjects
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SYSTEM dynamics , *DISSECTION , *RNA sequencing , *VELOCITY , *TIME management - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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