RNA velocity

Further information: RNA sequencing

RNA velocity is based on bridging measurements to a underlying mechanism, mRNA splicing, with two modes indicating the current and future state. It is a method used to predict the future gene expression of a cell based on the measurement of both spliced and unspliced transcripts of mRNA.

RNA velocity could be used to infer the direction of gene expression changes in single-cell RNA sequencing (scRNA-seq) data. It provides insights into the future state of individual cells by using the abundance of unspliced to spliced RNA transcripts. This ratio can indicate the transcriptional dynamics and potential fate of a cell, such as whether it is transitioning from one cell type to another or undergoing differentiation.

Software usage

There are several software tools available for RNA velocity analysis.Each of these tools has its own strengths and applications, so the choice of tool would depend on the specific requirements of your analysis:

velocyto

Velocyto is a package for the analysis of expression dynamics in single cell RNA seq data. In particular, it enables estimations of RNA velocities of single cells by distinguishing unspliced and spliced mRNAs in standard single-cell RNA sequencing protocols. It is the first paper proposed the concept of RNA velocity. velocyto predicted RNA velocity by solving the proposed differential equations for each gene. The authors envision future manifold learning algorithms that simultaneously fit a manifold and the kinetics on that manifold, on the basis of RNA velocity.

scVelo

scVelo is a method that solves the full transcriptional dynamics of splicing kinetics using a likelihood-based dynamical model. This generalizes RNA velocity to systems with transient cell states, which are common in development and in response to perturbations. scVelo was applied to disentangling subpopulation kinetics in neurogenesis and pancreatic endocrinogenesis. scVelo demonstrate the capabilities of the dynamical model on various cell lineages in hippocampal dentate gyrus neurogenesis and pancreatic endocrinogenesis.

cellDancer

cellDancer is a scalable deep neural network that locally infers velocity for each cell from its neighbors and then relays a series of local velocities to provide single-cell resolution inference of velocity kinetics. cellDancer improved the extisting hypothesis of kinetic rates of velocyto and scVelo, transcription rate was either a constant (velocyto model) or binary values (scVelo model), splicing and degradation rates were shared by all the genes and cells, which may have unpredictable performance, while cellDancer can predict the specific transcription, splicing and degradation rates of each gene in each cell through deep learning.

MultiVelo

MultiVelo is a differential equation model of gene expression that extends the RNA velocity framework to incorporate epigenomic data. MultiVelo uses a probabilistic latent variable model to estimate the switch time and rate parameters of chromatin accessibility and gene expression .

DeepVelo

DeepVelo is a neural network–based ordinary differential equation that can model complex transcriptome dynamics by describing continuous-time gene expression changes within individual cells. DeepVelo has been applied to public datasets from different sequencing platforms to (i) formulate transcriptome dynamics on different time scales, (ii) measure the instability of cell states, and (iii) identify developmental driver genes via perturbation analysis.

UnitVelo

UnitVelo is a statistical framework of RNA velocity that models the dynamics of spliced and unspliced RNAs via flexible transcription activities. UnitVelo supports the inference of a unified latent time across the transcriptome.