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HiCDiff: single-cell Hi-C data denoising with diffusion models.

Yanli WangJianlin Cheng
Published in: Briefings in bioinformatics (2024)
The genome-wide single-cell chromosome conformation capture technique, i.e. single-cell Hi-C (ScHi-C), was recently developed to interrogate the conformation of the genome of individual cells. However, single-cell Hi-C data are much sparser than bulk Hi-C data of a population of cells, and noise in single-cell Hi-C makes it difficult to apply and analyze them in biological research. Here, we developed the first generative diffusion models (HiCDiff) to denoise single-cell Hi-C data in the form of chromosomal contact matrices. HiCDiff uses a deep residual network to remove the noise in the reverse process of diffusion and can be trained in both unsupervised and supervised learning modes. Benchmarked on several single-cell Hi-C test datasets, the diffusion models substantially remove the noise in single-cell Hi-C data. The unsupervised HiCDiff outperforms most supervised non-diffusion deep learning methods and achieves the performance comparable to the state-of-the-art supervised deep learning method in terms of multiple metrics, demonstrating that diffusion models are a useful approach to denoising single-cell Hi-C data. Moreover, its good performance holds on denoising bulk Hi-C data.
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