PT - JOURNAL ARTICLE AU - Liu, Qiao AU - Zeng, Wanwen AU - Zhang, Wei AU - Wang, Sicheng AU - Chen, Hongyang AU - Jiang, Rui AU - Zhou, Mu AU - Zhang, Shaoting TI - Deep generative modeling and clustering of single cell Hi-C data AID - 10.1101/2022.07.19.500573 DP - 2022 Jan 01 TA - bioRxiv PG - 2022.07.19.500573 4099 - http://biorxiv.org/content/early/2022/07/20/2022.07.19.500573.short 4100 - http://biorxiv.org/content/early/2022/07/20/2022.07.19.500573.full AB - Deciphering 3D genome conformation is important for understanding gene regulation and cellular function at a spatial level. The recent advances of single cell Hi-C technologies have enabled the profiling of the 3D architecture of DNA within individual cell, which allows us to study the cell-to-cell variability of 3D chromatin organization. Computational approaches are in urgent need to comprehensively analyze the sparse and heterogeneous single cell Hi-C data. Here, we proposed scDEC-Hi-C, a new framework for single cell Hi-C analysis with deep generative neural networks. scDEC-Hi-C outperforms existing methods in terms of single cell Hi-C data clustering and imputation. Moreover, the generative power of scDEC-Hi-C could help unveil the heterogeneity of chromatin architecture across different cell types. We expect that scDEC-Hi-C could shed light on deepening our understanding of the complex mechanism underlying the formation of chromatin contacts. scDEC-Hi-C is freely available at https://github.com/kimmo1019/scDEC-Hi-C.Key pointsscDEC-Hi-C provides an end-to-end framework based on autoencoder and deep generative model to comprehensively analyze single cell Hi-C data, including low-dimensional embedding and clustering.Through a series of experiments including single cell Hi-C data clustering and structural difference identification, scDEC-Hi-C demonstrates suprioir performance over existing methods.In the downstream analysis of chromatin loops from single cell Hi-C data, scDEC-Hi-C is capable of significantly enhancing the ability for identifying single cell chromatin loops by data imputation.Competing Interest StatementThe authors have declared no competing interest.