Kennedy, V. E.; Roy, R.; Peretz, C.; Koh, A.; Tran, E.; Smith, C.; Olshen, A.

Motivation Recently, single cell DNA sequencing (scDNAseq) and multimodal profiling with the addition of cell surface antibodies (scDAbseq) have provided key insights into cancer heterogeneity. Scaling these technologies across large patient cohorts, however, is cost and time prohibitive. Multiplexing, in which cells from unique patients are pooled into a single experiment, offers a possible solution. While multiplexing methods exist for scRNAseq, accurate demultiplexing in scDNAseq remains an unmet need. Results Here, we introduce SNACS: Single-Nucleotide Polymorphism (SNP) and Antibody-based Cell Sorting. SNACS relies on a combination of patient level cell surface identifiers and natural variation in genetic polymorphisms to demultiplex scDNAseq data. We demonstrated the performance of SNACS on a dataset consisting of multi-sample experiments from patients with leukemia where we knew truth from single sample experiments from the same patients. Using SNACS, accuracy ranged from 0.948 to 0.991 vs 0.552 to 0.934 using demultiplexing methods from the single cell literature. Availability Implementation SNACS is available at https://github.com/olshena/SNACS.