bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Май 23, 2025

Understanding how transcription factors (TFs) orchestrate gene regulatory networks that define complex tissue structures is central to uncovering organization and disease mechanisms. Although spatial multiome technologies now enable in situ measurement of both transcriptional activity chromatin accessibility, existing computational methods either overlook context or are hindered by the high dropout rates characteristic such data. Here, we introduce E ykthyr , a framework integrates expression accessibility within spatially aware model identify TFs driving programs. mitigates effects leveraging interpretable, low-dimensional embeddings - linear with respect their input enabling robust identification scalable inference regulators. Applied across diverse datasets, consistently outperforms approaches, accurately identifying coordinate programs mouse brain development regulate T-cell states tumor microenvironments. establishes foundation for decoding interpret local intercellular signaling shape structure, offering insights into logic underlying health disease.

Язык: Английский