Multicondition and multimodal temporal profile inference during mouse embryonic development
- Ran Zhang1,2,
- Chengxiang Qiu1,
- Galina N. Filippova3,
- Gang Li1,2,
- Jay Shendure1,4,5,6,7,
- Jean-Philippe Vert8,
- Xinxian Deng3,
- William Stafford Noble1,9 and
- Christine M. Disteche3,10
- 1Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA;
- 2eScience Institute, University of Washington, Seattle, Washington 98195, USA;
- 3Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington 98195, USA;
- 4Brotman Baty Institute for Precision Medicine, University of Washington, Seattle, Washington 98195, USA;
- 5Howard Hughes Medical Institute, Seattle, Washington 98195, USA;
- 6Allen Discovery Center for Cell Lineage Tracing, Seattle, Washington 98109, USA;
- 7Seattle Hub for Synthetic Biology, Seattle, Washington 98109, USA;
- 8Owkin, New York, New York 10010, USA;
- 9Paul G. Allen School of Computer Science and Engineering, University of Washington, Seattle, Washington 98195, USA;
- 10Department of Medicine, University of Washington, Seattle, Washington 98195, USA
Abstract
The emergence of single-cell time-series data sets enables modeling of changes in various types of cellular profiles over time. However, because of 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 multi–data set and multimodal profiles across time, and extrapolate single-cell profiles in a missing modality. We apply 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.
Footnotes
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at https://www.genome.org/cgi/doi/10.1101/gr.279997.124.
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Freely available online through the Genome Research Open Access option.
- Received September 9, 2024.
- Accepted August 1, 2025.
This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
