Abstract
Application of the widely used droplet-based microfluidic technologies in single-cell sequencing often yields doublets, introducing bias to downstream analyses. Especially, doublet-detection methods for single-cell chromatin accessibility sequencing (scCAS) data have multiple assay-specific challenges. Therefore, we propose scIBD, a self-supervised iterative-optimizing model for boosting heterotypic doublet detection in scCAS data. scIBD introduces an adaptive strategy to simulate high-confident heterotypic doublets and self-supervise for doublet-detection in an iteratively optimizing manner. Comprehensive benchmarking on various simulated and real datasets demonstrates the outperformance and robustness of scIBD. Moreover, the downstream biological analyses suggest the efficacy of doublet-removal by scIBD.