Simultaneous modeling of chromatin conformation changes from multiple single-cell interaction maps with ChromMovie

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.