DOI: 10.1101/2023.05.24.542032

scGHOST: Identifying single-cell 3D genome subcompartments

K.Xiong R. Zhang J. Ma

摘要

New single-cell Hi-C (scHi-C) technologies enable probing of the genome-wide cell-to-cell variability in 3D genome organization from individual cells. Several computational methods have been developed to reveal single-cell 3D genome features based on scHi-C data, including A/B compartments, topologically-associating domains, and chromatin loops. However, no scHi-C analysis method currently exists for annotating single-cell subcompartments, which are crucial for providing a more refined view of large-scale chromosome spatial localization in single cells. Here, we present scGHOST, a single-cell subcompartment annotation method based on graph embedding with constrained random walk sampling. Applications of scGHOST to scHi-C data and single-cell 3D genome imaging data demonstrate the reliable identification of single-cell subcompartments and offer new insights into cell-to-cell variability of nuclear subcompartments. Using scHi-C data from the human prefrontal cortex, scGHOST identifies cell type-specific subcompartments that are strongly connected to cell type-specific gene expression, suggesting the functional implications of single-cell subcompartments. Overall, scGHOST is an effective new method for single-cell 3D genome subcompartment annotation based on scHi-C data for a broad range of biological contexts.

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