Multicondition and multimodal temporal profile inference during mouse embryonic development

  1. Christine Disteche2
  1. 1 University of Washington, eScience Institute;
  2. 2 University of Washington;
  3. 3 University of Washington, Howard Hughes Medical Institute, Allen Center for Cell Lineage Tracing;
  4. 4 Owkin
  • * Corresponding author; email: wnoble{at}uw.edu
  • Abstract

    The emergence of single-cell time-series datasets enables modeling of changes in various types of cellular profiles over time. However, due to the disruptive nature of single-cell measurements, it is impossible to capture the full temporal trajectory of a particular cell. Furthermore, single-cell profiles can be collected at mismatched time points across different conditions (e.g., sex, batch, disease) and data modalities (e.g., scRNA-seq, scATAC-seq), which makes modeling challenging. Here we propose a joint modeling framework, Sunbear, for integrating multicondition and multimodal single-cell profiles across time. Sunbear can be used to impute single-cell temporal profile changes, align multidataset and multimodal profiles across time, and extrapolate single-cell profiles in a missing modality. We applied Sunbear to reveal sex-biased transcription during mouse embryonic development and predict dynamic relationships between epigenetic priming and transcription for cells in which multimodal profiles are unavailable. Sunbear thus enables the projection of single-cell time-series snapshots to multimodal and multicondition views of cellular trajectories.

    • Received September 9, 2024.
    • Accepted August 1, 2025.

    This manuscript is Open Access.

    This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International license), as described at http://creativecommons.org/licenses/by/4.0/.

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    1. Genome Res. gr.279997.124 Published by Cold Spring Harbor Laboratory Press

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