Banecki Krzysztof H, Chai Haoxi, Ruan Yijun, Plewczynski Dariusz
Laboratory of Bioinformatics and Computational Genomics, Faculty of Mathematics and Information Science, Warsaw University of Technology, Koszykowa 75, 00-662, Warsaw, Poland.
Laboratory of Functional and Structural Genomics, Centre of New Technologies, University of Warsaw, Stefana Banacha 2c, 02-097, Warsaw, Poland.
bioRxiv. 2025 May 21:2025.05.16.654550. doi: 10.1101/2025.05.16.654550.
The development of 3C-based techniques for analyzing three-dimensional chromatin structure dynamics has driven significant interest in computational methods for 3D chromatin reconstruction. In particular, models based on Hi-C and its single-cell variants, such as scHi-C, have gained widespread popularity. Current approaches for reconstructing the chromatin structure from scHi-C data typically operate by processing one scHi-C map at a time, generating a corresponding 3D chromatin structure as output. Here, we introduce an alternative approach to the whole genome 3D chromatin structure reconstruction that builds upon existing methods while incorporating the broader context of dynamic cellular processes, such as the cell cycle or cell maturation. Our approach integrates scHi-C contact data with single-cell trajectory information and is based on applying simultaneous modeling of a number of cells ordered along the progression of a given cellular process. The approach is able to successfully recreate known nuclear structures while simultaneously achieving smooth, continuous changes in chromatin structure throughout the cell cycle trajectory. Although both Hi-C-based chromatin reconstruction and cellular trajectory inference are well-developed fields, little effort has been made to bridge the gap between them. To address this, we present ChromMovie, a comprehensive molecular dynamics framework for modeling 3D chromatin structure changes in the context of cellular trajectories. To our knowledge, no existing method effectively leverages both the variability of single-cell Hi-C data and explicit information from estimated cellular trajectories, such as cell cycle progression, to improve chromatin structure reconstruction.
用于分析三维染色质结构动态变化的基于3C的技术发展，激发了人们对三维染色质重建计算方法的浓厚兴趣。特别是基于Hi-C及其单细胞变体（如scHi-C）的模型已广受欢迎。目前从scHi-C数据重建染色质结构的方法通常是一次处理一个scHi-C图谱，生成相应的三维染色质结构作为输出。在此，我们介绍一种全基因组三维染色质结构重建的替代方法，该方法在现有方法的基础上构建，同时纳入了动态细胞过程（如细胞周期或细胞成熟）的更广泛背景。我们的方法将scHi-C接触数据与单细胞轨迹信息相结合，并基于对沿给定细胞过程进展排序的多个细胞进行同步建模。该方法能够成功重建已知的核结构，同时在整个细胞周期轨迹中实现染色质结构的平滑、连续变化。尽管基于Hi-C的染色质重建和细胞轨迹推断都是发展成熟的领域，但在弥合它们之间的差距方面所做的工作很少。为了解决这个问题，我们提出了ChromMovie，这是一个用于在细胞轨迹背景下对三维染色质结构变化进行建模的综合分子动力学框架。据我们所知，没有现有方法能有效利用单细胞Hi-C数据的变异性和来自估计细胞轨迹（如细胞周期进展）的明确信息来改进染色质结构重建。
