RNA velocity

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# RNA velocity
### <a href="https://csoneson.github.io">Charlotte Soneson</a>
### Computational Biology Platform, Friedrich Miescher Institute for Biomedical Research
### January 14, 2022

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# RNA velocity

* The gene expression profile of a cell often gives a good indication of the current state of the cell. However, being a single snapshot in time, it does not tell us in which _direction_ (in gene expression space) the cell is heading, or in what state it will be at some point in the near future.
* RNA velocity is one way of filling this gap - it is defined as the rate of change of the mature RNA abundance in a cell, and can be estimated from scRNA-seq data by joint modeling of estimated unspliced (pre-mRNA) and spliced (mature mRNA) abundances.

![](rna-velocity-figures/scvelo_example_dynmod.png)

<div class="my-footer"><span>https://scvelo.readthedocs.io/DynamicalModeling.html</span></div>

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# RNA velocity

![](rna-velocity-figures/BergenFig1a.png)

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* s - spliced/exonic/processed/mature mRNA abundance
* u - unspliced/intronic/unprocessed/pre-mRNA abundance
]

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![:scale 90%](rna-velocity-figures/RNAvelocityEquation.png)
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<div class="my-footer"><span>Zeisel et al (2011), La Manno et al (2018), Bergen et al (2020)</span></div>

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# Steady state and RNA velocity

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# Steady state and RNA velocity

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# Velocity estimation

* velocyto (R/python) - steady-state model
* scVelo (python) - steady-state, stochastic, dynamical models
* velociraptor (R wrapper for scVelo)

![:scale 85%](rna-velocity-figures/BergenFig1.jpg)

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# Input data

* Solving the system of ODEs requires abundance estimates for both mature mRNA and pre-mRNA - can't use "regular" gene expression estimation pipelines.
* For droplet scRNA-seq data, options include: 
    * alevin (or alevin-fry)
    * kallisto|bustools
    * STARsolo
    * velocyto

![](rna-velocity-figures/feature_reads.png)

<div class="my-footer"><span>La Manno et al (2018), Srivastava et al (2019), Melsted, Ntranos & Pachter (2019), Melsted et al (2019), He et al (2021), Kaminow et al (2021)</span></div>

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# What is an intron?

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![:scale 80%](rna-velocity-figures/intron_definition_2.001.png)
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# Example