ScAVENGERS: a genotype-based deconvolution of individuals in multiplexed single-cell ATAC-seq data without reference genotypes. Issue 4 (31st December 2022)

• Record Type: Journal Article
• Authors: Han, Seungbeom; Kim, Kyukwang; Park, Seongwan; Lee, Andrew J; Chun, Hyonho; Jung, Inkyung
• Is Part Of: NAR genomics and bioinformatics. Volume 4:Issue 4(2022)
• Publication Date: 2022-12-31
• Subjects: Genomics -- Periodicals; Bioinformatics -- Periodicals; 572.8
• DOI: 10.1093/nargab/lqac095
• Languages: English
• ISSNs: 2631-9268

Abstract

Abstract: Genetic differences inferred from sequencing reads can be used for demultiplexing of pooled single-cell RNA-seq (scRNA-seq) data across multiple donors without WGS-based reference genotypes. However, such methods could not be directly applied to single-cell ATAC-seq (scATAC-seq) data owing to the lower read coverage for each variant compared to scRNA-seq. We propose a new software, scATAC-seq Variant-based EstimatioN for GEnotype ReSolving (scAVENGERS), which resolves this issue by calling more individual-specific germline variants and using an optimized mixture model for the scATAC-seq. The benchmark conducted with three synthetic multiplexed scATAC-seq datasets of peripheral blood mononuclear cells and prefrontal cortex tissues showed outstanding performance compared to existing methods in terms of accuracy, doublet detection, and a portion of donor-assigned cells. Furthermore, analyzing the effect of the improved sections provided insight into handling pooled single-cell data in the future. Our source code of the devised software is available at GitHub: https://github.com/kaistcbfg/scAVENGERS .