1/🚀 Excited to share RegVelo, our new cell model combining RNA velocity with gene regulatory network (GRN) dynamics to model cellular changes and predict in silico perturbations. Here's how it works and why it matters! 🧵👇 biorxiv.org/content/10.1101/2024.12.11.627935v1 - ThreadSky

fabiantheis.bsky.social • 189 days ago

1/🚀 Excited to share RegVelo, our new cell model combining RNA velocity with gene regulatory network (GRN) dynamics to model cellular changes and predict in silico perturbations. Here's how it works and why it matters! 🧵👇
https://biorxiv.org/content/10.1101/2024.12.11.627935v1

Comments

gioelelamanno.bsky.social•188 days ago

Congrats! Cool work!

alienbeach.bsky.social•188 days ago

Very impressive work.

fabiantheis.bsky.social•189 days ago

2/ Why RegVelo?
RNA velocity is a powerful concept for ~mechanistic modeling of cell dynamics, but existing methods ignore gene-gene interactions. Tools like Pando, CellOracle, and Dynamo treat GRNs separately w/o their dynamics, potentially limiting their ability to generalize.

fabiantheis.bsky.social•189 days ago

3/ To bridge the gap between cellular dynamics and gene regulation, we present RegVelo, an end-to-end deep learning framework integrating GRN-informed transcription into genome-wide models of splicing dynamics.

fabiantheis.bsky.social•189 days ago

4/ How does RegVelo perform?
We validated RegVelo on:
• Simulated & cell-cycle data (with ground truth)
• Murine pancreatic endocrinogenesis
• Human hematopoiesis
• Zebrafish development
It faithfully maps cellular changes & identifies lineage drivers! 🔬

fabiantheis.bsky.social•189 days ago

5/ Hematopoiesis is a prime example of a well-studied system where std RNA velocity fails due to its dynamic regulation. We showed that RegVelo overcomes this limitation, validated our inferred GRN, and rediscovered known key regulators with our in-silico perturbation scheme.

fabiantheis.bsky.social•189 days ago

6/ We further applied RegVelo to zebrafish neural crest development, generating new single-cell experiments (Smart-Seq3, 10x, Perturb-seq). Using RegVelo, we identified tfec & elf1 as key regulators for the pigment lineage and experimentally validated their roles. 🐟

fabiantheis.bsky.social•189 days ago

7/ Why it matters:
RegVelo isn’t just about modeling—it’s actionable.
It allows systematic in silico perturbations of cell dynamics that can guide experimental designs and uncover mechanisms driving cellular fate. 🚀

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