28 / 2026-03-14 16:57:59

Detecting A/B Compartments and Subcompartments from Single-Cell Hi-C Matrices

single-cell Hi-C,A/B compartment,subcompartment,Statistical Analysis,chromatin organization

Single-cell Hi-C (scHi-C) provides unprecedented insight into 3D genome organization, but its

sparse and noisy data pose challenges in accurately detecting A/B compartments and subcom-

partments, which are crucial for understanding chromatin structure and gene regulation.

    For A/B compartments, we presented scDIAGRAM, a data-driven method for annotating A/B

compartments in single cells using direct statistical modeling and graph community detection.

Unlike existing approaches, scDIAGRAM infers chromatin compartments directly from individ-

ual scHi-C matrix without imputation or external reference features (only used for A/B labeling).

Accuracy of scDIAGRAM was illustrated through simulated scHi-C datasets and a human cell

line. For real datasets, we applied scDIAGRAM to the HiRES data from the mouse brain cortex,

mouse embryonic development, and human acute myeloid leukemia (AML), demonstrating its

ability to capture compartmental shifts associated with transcriptional variation.

      For subcompartments, we presented scSTEC, which constructed a simplified 2D genomic locus

embedding and took a consensus across chromosomes. Inspired by scGHOST, scSTEC over-

came the need of reliable inter-chromosomal contact matrices in scHi-C data when computing

subcompartments. The inputs of scSTEC were A/B compartments and imputed scHi-C matrices,

for each chromosome scSTEC constructed a simplified 2D embedding using other chromosomes

for correction; followed by clustering, labeling and cross-chromosome consensus to obtain ul-

timate subcompartments. Validation on simulated data and cell line GM12878 revealed the

accuracy and efficiency of scSTEC. Applied to scHi-C datasets with complex tissues, scSTEC

revealed subcompartmental dynamics across different cell types and developmental stages.

     Overall, these robust frameworks offer new insights into the functional roles of chromatin compartments

at single-cell resolution across various biological contexts.