ScHiCAtt: Enhancing Single-Cell Hi-C Resolution Using Attention-Based Models

Abstract

The spatial organization of chromatin is fundamental to gene regulation and essential for proper cellular function. The Hi-C technique remains the leading method for unraveling 3D genome structures; however, limited resolution, data sparsity, and incomplete coverage in single-cell Hi-C data pose significant challenges for comprehensive analysis. Traditional CNN-based models often suffer from blurring and loss of fine details, while GAN-based methods encounter difficulties in maintaining diversity and generalization. Moreover, existing algorithms perform poorly in cross-cell line generalization, where a model trained on one cell type is used to enhance high-resolution data in another cell type. To address these limitations, we propose ScHiCAtt (Single-cell Hi-C Attention-Based Model), which leverages attention mechanisms to capture both long-range and local dependencies in Hi-C data, significantly enhancing resolution while preserving biologically meaningful interactions. We implement this mechanism and check its validity on data from different cells of the same organisms and data of different organisms. By dynamically focusing on regions of interest, attention mechanisms effectively mitigate data sparsity and enhance model performance in low-resolution contexts. Extensive experiments on Human and Drosophila single-cell Hi-C data demonstrate that ScHiCAtt consistently outperforms existing methods in terms of computational and biological reproducibility metrics across different downsampling ratios, especially under extreme downsampling conditions. The model is publicly available at https://github.com/OluwadareLab/ScHiCAtt.