OddSNP: a predictive framework for optimizing multiplexed single-cell RNA-seq experiments.

ABSTRACT: Donor multiplexing is a powerful strategy to increase scale, lower the costs, and reduce batch effects in single-cell RNA sequencing (scRNAseq), but clear guidelines for experimental design are lacking, forcing researchers to risk costly demultiplexing failures. To address this, we introduce SNP-Information Content (SNP-IC), a quantitative metric computable from simple unpooled pilot data that accurately predicts the success of genotype-based demultiplexing. Across multiple large-scale datasets using stem cell and organoid models, we establish a robust SNP-IC threshold of approximately 50, above which cells can be reliably assigned to their donor of origin. For more challenging genotype-free approaches, we define a pairwise metric, cpSNP-IC, and demonstrate a much higher requirement of app

SUBMITTER: Allendes Osorio RS 

PROVIDER: S-EPMC12710642 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature