
==== Front
bioRxiv
BIORXIV
bioRxiv
2692-8205
Cold Spring Harbor Laboratory

10.1101/2024.08.29.610389
preprint
1
Article
Variational inference of single cell time series
Xu Bingxian http://orcid.org/0000-0003-0406-563X

Braun Rosemary http://orcid.org/0000-0001-9668-9866

30 8 2024
2024.08.29.610389https://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License, which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use.
http://biorxiv.org/lookup/doi/10.1101/2024.08.29.610389
nihpp-2024.08.29.610389.pdf
Abstract

Time course single–cell RNA sequencing (scRNA-seq) enables researchers to probe genome–wide expression dynamics at the the single cell scale. However, when gene expression is affected jointly by time and cellular identity, analyzing such data — including conducting cell type annotation and modeling cell type–dependent dynamics — becomes challenging. To address this problem, we propose SNOW (SiNgle cell flOW map), a deep learning algorithm to deconvolve single cell time series data into time– dependent and time–independent contributions. SNOW has a number of advantages. First, it enables cell type annotation based on the time–independent dimensions. Second, it yields a probabilistic model that can be used to discriminate between biological temporal variation and batch effects contaminating individual timepoints, and provides an approach to mitigate batch effects. Finally, it is capable of projecting cells forward and backward in time, yielding time series at the individual cell level. This enables gene expression dynamics to be studied without the need for clustering or pseudobulking, which can be error prone and result in information loss. We describe our probabilistic framework in detail and demonstrate SNOW using data from three distinct time course scRNA-seq studies. Our results show that SNOW is able to construct biologically meaningful latent spaces, remove batch effects, and generate realistic time–series at the single–cell level. By way of example, we illustrate how the latter may be used to enhance the detection of cell type–specific circadian gene expression rhythms, and may be readily extended to other time–series analyses.
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