COCOA: A Framework for Fine-scale Mapping of Cell-type-specific Chromatin Compartments Using Epigenomic Information

Chromatin compartmentalization and epigenomic modifications play crucial roles in cell differentiation and disease development. However, precise mapping of chromatin compartment patterns requires Hi-C or Micro-C data at high sequencing depth. Exploring the systematic relationship between epigenomic modifications and compartment patterns remains challenging. To address these issues, we present COCOA, a deep neural network framework using convolution and attention mechanisms to infer fine-scale chromatin compartment patterns from six histone modification signals. COCOA extracts 1D track features through bidirectional feature reconstruction after resolution-specific binning of epigenomic signals. These track features are then cross-fused with contact features using an attention mechanism and transformed into chromatin compartment patterns through residual feature reduction. COCOA demonstrates accurate inference of chromatin compartmentalization at a fine-scale resolution and exhibits stable performance on test sets. Additionally, we explored the impact of histone modifications on chromatin compartmentalization prediction through in silico epigenomic perturbation experiments. Unlike obscure compartments observed in high-depth experimental data at 1-kb resolution, COCOA generates clear and detailed compartment patterns, highlighting its superior performance. Finally, we demonstrate that COCOA enables cell-type-specific prediction of unrevealed chromatin compartment patterns in various biological processes, making it an effective tool for gaining insights into chromatin compartmentalization from epigenomics in diverse biological scenarios. The COCOA Python code is publicly available at https://github.com/onlybugs/COCOA and https://ngdc.cncb.ac.cn/biocode/tools/BT007498.