Integrated ambient modeling and genetic demultiplexing of single-cell RNA+ATAC multiome experiments with Ambimux.

ABSTRACT: Single cell technologies have advanced at a rapid pace, providing assays for various molecular phenotypes. Droplet-based single cell technologies, particularly those based on nuclei isolation, such as simultaneous RNA+ATAC single-cell multiome, are susceptible to exogenous ambient molecule contamination, which can increase noise in cell type-level associations. We reasoned that genotype-based sample multiplexing can provide an opportunity to infer this ambient contamination by leveraging DNA variation in sequenced reads. Thus, we developed ambimux, a likelihood-based method to estimate ambient fractions and demultiplex single-cell multiome experiments using genotype-level data. Ambimux models the ambient or nuclear probability at the read level and thus can classify empty droplets and esti

SUBMITTER: Alvarez M 

PROVIDER: S-EPMC12407767 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature