RNA velocity has enabled the recovery of directed dynamic information from single-cell transcriptomics by connecting measurements to the underlying kinetics of gene expression. This approach has opened up new ways of studying cellular dynamics. Researchers from the Helmholtz Center Munich discuss the current state of RNA velocity modeling approaches, discuss various examples illustrating limitations and potential pitfalls, and provide guidance on how the ensuing challenges may be addressed. The researchers then outline future directions on how to generalize the concept of RNA velocity to a wider variety of biological systems and modalities.
Current state of RNA velocity modeling
(A) Transcription of pre-mRNAs, their conversion into spliced mRNAs, and eventual degradation. Current RNA velocity modeling approaches use basic reaction kinetics for each gene independently and formulate deterministic differential equations with linear dependencies, assuming constant rates. The system is decoupled across genes and does not account for transcriptional regulation. (B) The temporal response delay of pre-mRNA being spliced into mature mRNA manifests itself in the curvature in phase space and is leveraged to model and estimate RNA velocity for each gene. Velocity is obtained from the residual of the observed ratio to the inferred steady-state ratio, i.e., the ratio of degradation to splicing rate. (C) The combination of velocities across genes is used to extrapolate the future state of an individual cell.