Regulatory-prior-guided attention preserves biological structure during unpaired single-cell RNA-ATAC integration.

Regulatory-prior-guided attention in scHPGT enhances biological structure preservation during unpaired RNA and ATAC data integration, outperforming existing methods across multiple benchmarks.

• Why it matters: Integrating unpaired single-cell RNA and ATAC profiles is crucial for understanding gene regulation but is hindered by differences in feature space, sparsity, and noise, risking inaccurate biological interpretations.
• What they did: scHPGT employs modality-specific encoders, a regulatory-prior-guided cross-modal Transformer, and a domain-adversarial objective to align data while preserving biological structures, tested on diverse datasets with over 10,000 cells.
• The result: The approach improves clustering, label transfer, and regulatory relationship recovery, enabling accurate identification of cell types and regulatory programs without forcing mismatched states, facilitating deeper biological insights.