Biology subjects

Weiler, P.

Publications and source records attributed to Weiler, P..

3 recordsLinked to original sources

bioRxiv2022

Modeling Single-Cell Dynamics Using Unbalanced Parameterized Monge Maps

Optimal Transport (OT) has proven useful to infer single-cell trajectories of developing biological systems by aligning distributions across time points. Recently, Parameterized Monge Maps (PMM) were introduced to learn the optimal map between two distributions. Here, we apply PMM to model single-cell dynamics and show that PMM fails to account for asymmetric shifts in cell state distributions. To alleviate this limitation, we propose Unbalanced Parameterised Monge Maps (UPMM). We first describe the novel formulation and show on synthetic data how our method extends discrete unbalanced OT to the continuous domain. Then, we demonstrate that UPMM outperforms well-established trajectory inference methods on real-world developmental single-cell data.

bioinformatics↗

bioRxiv2022

Deep generative modeling of transcriptional dynamics for RNA velocity analysis in single cells

RNA velocity has been rapidly adopted to guide the interpretation of transcriptional dynamics in snapshot single-cell transcriptomics data. Current approaches for estimating and analyzing RNA velocity can empirically reveal complex dynamics but lack effective strategies for quantifying the uncertainty of the estimate and its overall applicability to the system of interest. Here, we present veloVI (velocity variational inference), a deep generative modeling framework for estimating RNA velocity. veloVI learns a gene-specific dynamical model of RNA metabolism and provides a transcriptome-wide quantification of velocity uncertainty. We show in a series of examples that veloVI compares favorably to previous approaches for inferring RNA velocity with improvements in fit to the data, consistency across transcriptionally similar cells, and stability across preprocessing pipelines for quantifying RNA abundance. Further, we demonstrate that properties unique to veloVI, such as posterior velocity uncertainty, can be used to assess the appropriateness of analysis with velocity to the data at hand. Finally, we highlight veloVI as a flexible framework for modeling transcriptional dynamics by adapting the underlying dynamical model to use time-dependent transcription rates.

bioinformatics↗

bioRxiv2021

A guide to trajectory inference and RNA velocity

Technological developments have led to an explosion of high-throughput single cell data, which are revealing unprecedented perspectives on cell identity. Recently, significant attention has focused on investigating, from single-cell RNA-sequencing (scRNA-seq) data, cellular dynamic processes, such as cell differentiation, cell cycle and cell (de)activation. Trajectory inference methods estimate a trajectory, a collection of differentiation paths of a dynamic system, by ordering cells along the paths of such a dynamic process. While trajectory inference tools typically work with gene expression levels, common scRNA-seq protocols allow the identification and quantification of unspliced pre-mRNAs and mature spliced mRNAs, for each gene. By exploiting the abundance of unspliced and spliced mRNA, one can infer the RNA velocity of individual cells, i.e., the time derivative of the gene expression state of cells. Whereas traditional trajectory inference methods reconstruct cellular dynamics given a population of cells of varying maturity, RNA velocity relies on a dynamical model describing splicing dynamics. Here, we initially discuss conceptual and theoretical aspects of both approaches, then illustrate how they can be combined together, and finally present an example use-case on real data.

bioinformatics↗