通过多尺度计算建模研究基因组折叠中的相分离
Investigating Phase Separation in Genome Folding via Multiscale Computational Modeling.
摘要(中文译文)
基因组的三维组织对基因调控至关重要，而相分离已成为解释这一结构的重要物理原理。本综述综合阐述了相分离如何在从区室化分离和拓扑关联结构域到转录凝聚体和核小体阵列的各个尺度上促进基因组折叠，并特别关注计算方面的进展。我们将该领域归纳为两种互补的建模范式：（1）基于物理的模拟，涵盖从全原子到粗粒化聚合物表示，揭示驱动染色质凝聚的机制；（2）数据驱动方法，包括机器学习，从高通量基因组和成像数据中学习结构特征和调控相互作用。我们强调将这些模型与实验相结合如何阐明相分离、环挤出、表观遗传修饰以及染色质固有聚合物特性在基因组折叠中的相互作用。通过将微观分子相互作用与中尺度和核组织联系起来，这些联合方法为正常调控及其在疾病中的失调提供了机制性见解，并勾勒出通向四维核组预测性非平衡模型的道路。
Abstract
The 3D organization of the genome is central to gene regulation, and phase separation has emerged as an important physical principle for this architecture. This review synthesizes how phase separation contributes to genome folding across scales, from compartmental segregation and topologically associating domains to transcriptional condensates and nucleosome arrays, with a special focus on computational advances. We organize the field into two complementary modeling paradigms: (1) physics-based simulations, spanning all-atom to coarse-grained polymer representations that reveal the mechanisms driving chromatin condensation; and (2) data-driven approaches, including machine learning, that learn structural features and regulatory interactions from high-throughput genomic and imaging data. We highlight how integrating these models with experiments clarifies the interplay among phase separation, loop extrusion, epigenetic modifications, and the intrinsic polymer properties of chromatin in genome folding. By linking microscopic molecular interactions to mesoscale and nuclear organization, these combined approaches provide mechanistic insight into normal regulation and its dysregulation in disease, and they chart a path toward predictive, non-equilibrium models of the 4D nucleome.
如何引用
AMA
Jiahu Tang, Cibo Feng, Haibin Su, Xiakun Chu. Investigating Phase Separation in Genome Folding via Multiscale Computational Modeling.. Advanced science (Weinheim, Baden-Wurttemberg, Germany). 2026; doi:10.1002/advs.74997.
APA
Jiahu Tang, Cibo Feng, Haibin Su, Xiakun Chu (2026). Investigating Phase Separation in Genome Folding via Multiscale Computational Modeling.. Advanced science (Weinheim, Baden-Wurttemberg, Germany). https://doi.org/10.1002/advs.74997
GB/T 7714
Jiahu Tang, Cibo Feng, Haibin Su, Xiakun Chu. Investigating Phase Separation in Genome Folding via Multiscale Computational Modeling.[J]. Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026 doi:10.1002/advs.74997.
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