scACT: Accurate Cross-modality Translation via Cycle-consistent Training from Unpaired Single-cell Data.

Single-cell sequencing technologies have revolutionized genomics by enabling the simultaneous profiling of various molecular modalities within individual cells. Their integration, especially cross-modality translation, offers deep insights into cellular regulatory mechanisms. Many methods have been developed for cross-modality translation, but their reliance on scarce high-quality co-assay data limits their applicability. Addressing this, we introduce scACT, a deep generative model designed to extract cross-modality biological insights from unpaired single-cell data. scACT tackles three major challenges: aligning unpaired multi-modal data via adversarial training, facilitating cross-modality translation without prior knowledge via cycle-consistent training, and enabling interpretable regulatory interconnections explorations via in-silico perturbations. To test its performance, we applied scACT on diverse single-cell datasets and found it outperformed existing methods in all three tasks. Finally, we have developed scACT as an individual open-source software package to advance single-cell omics data processing and analysis within the research community.