徐炳祥 (2025-02-28 08:54):
#paper doi:10.1073/pnas.1901423116 Proc Natl Acad Sci USA, 2019, Robust single-cell Hi-C clustering by convolution- and random-walk-based imputation。近年来,单细胞Hi-C技术已经称为三维基因组学研究的新热点。然而受限于单细胞技术的固有缺陷,单细胞Hi-C文库普遍存在严重的测序深度不足和较大的细胞间变异性。因此有必要对原始数据加以修正和填补,本文提出在卷积平滑的基础上附加random walk with restart过程的数据填补,填补后的数据保留了染色质空间构象的各组织特征,同时实现了细胞类型间的更好区分。本文在单细胞Hi-C生物信息学中有重要地位,其提出的思路为后续多项研究所借鉴。
Robust single-cell Hi-C clustering by convolution- and random-walk–based imputation
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Abstract:
Three-dimensional genome structure plays a pivotal role in gene regulation and cellular function. Single-cell analysis of genome architecture has been achieved using imaging and chromatin conformation capture methods such as Hi-C. To study variation in chromosome structure between different cell types, computational approaches are needed that can utilize sparse and heterogeneous single-cell Hi-C data. However, few methods exist that are able to accurately and efficiently cluster such data into constituent cell types. Here, we describe scHiCluster, a single-cell clustering algorithm for Hi-C contact matrices that is based on imputations using linear convolution and random walk. Using both simulated and real single-cell Hi-C data as benchmarks, scHiCluster significantly improves clustering accuracy when applied to low coverage datasets compared with existing methods. After imputation by scHiCluster, topologically associating domain (TAD)-like structures (TLSs) can be identified within single cells, and their consensus boundaries were enriched at the TAD boundaries observed in bulk cell Hi-C samples. In summary, scHiCluster facilitates visualization and comparison of single-cell 3D genomes.
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