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scDIAGRAM: detecting chromatin compartments from individual single-cell Hi-C matrix without imputation or reference
Yongli Peng1, Yujing Deng2, Menghan Liu2
1Beijing International Center for Mathematical Research (BICMR), Peking University, No.5 Yiheyuan Road, Haidian District, Beijing 100871, China.
Briefings in Bioinformatics
|March 8, 2026
Summary
We developed scDIAGRAM, a novel method to accurately identify A/B compartments in single-cell Hi-C (scHi-C) data. This approach enhances understanding of 3D genome organization and gene regulation at the single-cell level.
Area of Science:
- Genomics
- Epigenetics
- Computational Biology
Background:
- Single-cell Hi-C (scHi-C) data reveals 3D genome organization but is sparse and noisy.
- Accurate detection of A/B compartments is vital for understanding chromatin structure and gene regulation.
- Existing methods face challenges with scHi-C data sparsity and noise.
Purpose of the Study:
- To present scDIAGRAM, a data-driven computational method for annotating A/B compartments in single cells.
- To overcome limitations of existing methods in analyzing sparse scHi-C data.
- To enable robust analysis of chromatin compartments at single-cell resolution.
Main Methods:
- scDIAGRAM utilizes direct statistical modeling and graph community detection on individual scHi-C matrices.
- The method infers chromatin compartments without imputation or external reference features.
- A/B labels are assigned using conventional genomic annotations.
Main Results:
- scDIAGRAM demonstrated accuracy and robustness on simulated and real scHi-C datasets.
- The method successfully identified A/B compartments in human cell lines.
- Application to mouse and human datasets revealed compartmental shifts linked to transcriptional variation.
Conclusions:
- scDIAGRAM provides a robust framework for analyzing A/B compartments in single-cell resolution.
- This method offers new insights into the functional roles of chromatin compartments across diverse biological contexts.
- scDIAGRAM advances the study of 3D genome organization and its impact on gene regulation.
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