Bulletin of the American Physical Society
APS March Meeting 2023
Volume 68, Number 3
Las Vegas, Nevada (March 5-10)
Virtual (March 20-22); Time Zone: Pacific Time
Session N10: Cell Fate Transitions
11:30 AM–2:30 PM,
Wednesday, March 8, 2023
Room: Room 202
Sponsoring
Unit:
DBIO
Chair: Jianhua Xing, University of Pittsburgh; Sahand Rahi, Ecole Polytechnique Federale de Lausanne
Abstract: N10.00003 : Bursty RNA Velocity of Gene Programs for Trajectory Inference
12:18 PM–12:30 PM
Presenter:
Frank Gao
(University of Chicago)
Authors:
Frank Gao
(University of Chicago)
Suriyanarayanan Vaikuntanathan
(University of Chicago)
Samantha Riesenfeld
(University of Chicago)
Advances in single-cell RNA sequencing (scRNA-seq) allow collections of tens of thousands cells undergoing differentiation or experiencing external stimuli, revealing a detailed picture of stochasticity of gene expression. This permits trajectory inference (TI) which leverages variation in transcriptional profiles to assign an order of progression to cells, enabling a temporal interpretation of cell state. Traditional TI methods are data-driven and ignore the underlying biological processes so the directionality of developmental courses must be provided as inputs. While the standard RNA velocity method has provided additional insights, its moments-based coarse-grained setup has led to results that are contradictory to experiments. Here, we introduce a new RNA velocity model which accounts for transcriptional bursting and infers kinetic parameters using the joint distributions of counts. Furthermore, our model incorporates topic modeling, a popular method to explore gene programs, which helps delineate dynamical patterns of local gene programs not observed on the global scale. By disentangling the intertwining dynamics of genes, our method provides crucial mechanistic insights for cell fate commitments.
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