category
bioRxiv
date
Feb 25, 2026
slug
status
Published
summary
提出多模态深度学习框架ChIANet,首次实现仅依赖蛋白质结合图谱预测染色质接触图和环结构;整合Transformer长距离建模与多任务学习,首次揭示不同蛋白质(CTCF/Cohesin/RNAPII)介导的染色质结构在保守性与可塑性上的差异;首次发现RNAPII介导的染色质环与癌症中ecDNA的强关联。
tags
蛋白质组学
空间组学
type
Post

📄 原文题目

Deep learning framework ChIANet predicts protein-mediated chromatin architecture across functional contexts

🔗 原文链接

💡 AI 核心解读

提出多模态深度学习框架ChIANet,首次实现仅依赖蛋白质结合图谱预测染色质接触图和环结构;整合Transformer长距离建模与多任务学习,首次揭示不同蛋白质(CTCF/Cohesin/RNAPII)介导的染色质结构在保守性与可塑性上的差异;首次发现RNAPII介导的染色质环与癌症中ecDNA的强关联。

📝 英文原版摘要

The spatial organization of the genome is dynamically shaped by chromatin-binding proteins, yet how protein-mediated three-dimensional (3D) architectures are specified across functional contexts remains incompletely understood. Here we present ChIANet, a multimodal deep learning framework that enables de novo prediction of protein-mediated chromatin contact maps and loops from protein-binding profiles alone, using the reference genome sequence as a prior. By integrating transformer-based long-range modeling with multi-task learning, ChIANet accurately reconstructs protein-mediated 3D chromatin architectures and generalizes across diverse cellular contexts. Systematic application of ChIANet to CTCF, Cohesin and RNAPII across seven human cell types reveals that chromatin architectures follow conserved organizational principles while exhibiting pronounced context-dependent reconfiguration: CTCF- and Cohesin-mediated interactions predominantly support stable structural frameworks, whereas RNAPII-mediated loops display greater variability and are closely coupled to transcriptional programs and regulatory element activity. Functional analyses further uncover distinct regulatory biases and super-enhancer associations among the three proteins. Extending this framework to cancer genomes, ChIANet captures RNAPII-mediated chromatin looping networks associated with extrachromosomal DNA (ecDNA), revealing highly connected, transcription-associated architectures within amplified ecDNA regions across multiple cancer cell types. Together, these results demonstrate that protein-mediated 3D genome organization is not determined by protein identity alone but is flexibly shaped by functional context, regulatory targets and cellular environment, establishing ChIANet as a unified and scalabl
e approach for decoding context-dependent principles of genome folding.
通过染色质状态近似引导干细胞分化鉴定连接DNA损伤应答过程的FANCD2相互作用蛋白基序(DIP-box)
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