Multicondition and multimodal temporal profile inference during mouse embryonic development

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.