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bioRxiv · 10.1101/2024.02.07.579345

Single Nucleotide Polymorphism (SNP) and Antibody-based Cell Sorting (SNACS): A tool for demultiplexing single-cell DNA sequencing data

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

MotivationRecently, single-cell DNA sequencing (scDNA-seq) and multi-modal profiling with the addition of cell-surface antibodies (scDAb-seq) 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. ResultsHere, 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 - 0.991 vs 0.552 - 0.934 using demultiplexing methods from the single-cell literature. Availability ImplementationSNACS is available at https://github.com/olshena/SNACS. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=83 SRC="FIGDIR/small/579345v1_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@1e52aaorg.highwire.dtl.DTLVardef@c51d1dorg.highwire.dtl.DTLVardef@fa68a6org.highwire.dtl.DTLVardef@1ec6bd1_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Kennedy, V. E., Roy, R., Peretz, C., Koh, A., Tran, E., Smith, C., Olshen, A.. 2024-02-10. Single Nucleotide Polymorphism (SNP) and Antibody-based Cell Sorting (SNACS): A tool for demultiplexing single-cell DNA sequencing data. https://doi.org/10.1101/2024.02.07.579345

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