Mapping transcriptional responses to cellular perturbation dictionaries with RNA fingerprinting.

ABSTRACT: Single-cell perturbation dictionaries provide systematic measurements of how cells respond to genetic and chemical perturbations, and create the opportunity to assign causal interpretations to observational data. Here, we introduce RNA fingerprinting, a statistical framework that maps transcriptional responses from new experiments onto reference perturbation dictionaries. RNA fingerprinting learns denoised perturbation "fingerprints" from single-cell data, then probabilistically assigns query cells to one or more candidate perturbations while accounting for uncertainty. We benchmark our method across ground-truth datasets, demonstrating accurate assignments at single-cell resolution, scalability to genome-wide screens, and the ability to resolve combinatorial perturbations. We demonstrate

SUBMITTER: Grabski IN 

PROVIDER: S-EPMC12458102 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature