CREATE: cell-type-specific cis-regulatory element identification via discrete embedding.

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Tác giả: Shengquan Chen, Xiaoyang Chen, Xuejian Cui, Zijing Gao, Rui Jiang, Zhen Li, Qiao Liu, Hairong Lv, Qijin Yin, Wanwen Zeng

Ngôn ngữ: eng

Ký hiệu phân loại: 616.9803 Other diseases

Thông tin xuất bản: England : Nature communications , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 746477

Cis-regulatory elements (CREs), including enhancers, silencers, promoters and insulators, play pivotal roles in orchestrating gene regulatory mechanisms that drive complex biological traits. However, current approaches for CRE identification are predominantly sequence-based and typically focus on individual CRE types, limiting insights into their cell-type-specific functions and regulatory dynamics. Here, we present CREATE, a multimodal deep learning framework based on Vector Quantized Variational AutoEncoder, tailored for comprehensive CRE identification and characterization. CREATE integrates genomic sequences, chromatin accessibility, and chromatin interaction data to generate discrete CRE embeddings, enabling accurate multi-class classification and robust characterization of CREs. CREATE excels in identifying cell-type-specific CREs, and provides quantitative and interpretable insights into CRE-specific features, uncovering the underlying regulatory codes. By facilitating large-scale prediction of CREs in specific cell types, CREATE enhances the recognition of disease- or phenotype-associated biological variabilities of CREs, thus advancing our understanding of gene regulatory landscapes and their roles in health and disease.
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