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Chen Su

Doctorat - McGill
Superviseur⋅e principal⋅e
Amin Emad
Sujets de recherche
Apprentissage profond
Biologie computationnelle
Réseaux de neurones en graphes

Publications

CellPace: A temporal diffusion-forcing framework for simulation, interpolation and forecasting of single-cell dynamics
Chen Su
Amin Emad
Abstract Single-cell omics technologies resolve cellular heterogeneity at high resolution but provide only static snapshots of continuous de… (voir plus)velopmental processes. This makes it difficult to recover coherent temporal dynamics when developmental stages are irregularly sampled or missing. While recent generative models can simulate observed cell states, they often treat timepoints as discrete categories, hindering interpolation across gaps and extrapolation to unobserved future stages. We present CellPace, a generative model that learns and generates developmental dynamics by leveraging a transformer-based temporal diffusion backbone conditioned on continuous, gap-aware temporal encodings. Across diverse mouse developmental lineages, CellPace achieves state-of-the-art performance in simulation, interpolation, and forecasting tasks. Beyond recovering global population statistics, generated cells preserve fine-grained biological structure, retaining dynamic gene regulatory programs and mapping accurately to anatomical regions in spatial transcriptomics data. Furthermore, CellPace extends naturally to multi-modal data, modeling joint RNA-chromatin dynamics even when temporal ordering is inferred from pseudotime. Together, these results position CellPace as a robust framework for modeling and generating continuous developmental dynamics from sparse, cross-sectional single-cell data.
2026-02-25
bioRxiv (prépublication)
doi.org
Deciphering lineage-relevant gene regulatory networks during endoderm formation by InPheRNo-ChIP
Chen Su
William A. Pastor
Amin Emad
Deciphering the underlying gene regulatory networks (GRNs) that govern early human embryogenesis is critical for understanding developmental… (voir plus) mechanisms yet remains challenging due to limited sample availability and the inherent complexity of the biological processes involved. To address this, we developed InPheRNo-ChIP, a computational framework that integrates multimodal data, including RNA-seq, transcription factor (TF)–specific ChIP-seq, and phenotypic labels, to reconstruct phenotype-relevant GRNs associated with endoderm development. The core of this method is a probabilistic graphical model that models the simultaneous effect of TFs on their putative target genes to influence a particular phenotypic outcome. Unlike the majority of existing GRN inference methods that are agnostic to the phenotypic outcomes, InPheRNo-ChIP directly incorporates phenotypic information during GRN inference, enabling the distinction between lineage-specific and general regulatory interactions. We integrated data from three experimental studies and applied InPheRNo-ChIP to infer the GRN governing the differentiation of human embryonic stem cells into definitive endoderm. Benchmarking against a scRNA-seq CRISPRi study demonstrated InPheRNo-ChIP’s ability to identify regulatory interactions involving endoderm markers FOXA2, SMAD2, and SOX17, outperforming other methods. This highlights the importance of incorporating the phenotypic context during network inference. Furthermore, an ablation study confirms the synergistic contribution of ChIP-seq, RNA-seq, and phenotypic data, highlighting the value of multimodal integration for accurate phenotype-relevant GRN reconstruction.
2023-12-31
Briefings Bioinform. (publié)
doi.org