Systematic reconstruction of molecular pathway signatures using scalable single-cell perturbation screens.

ABSTRACT: Recent advancements in functional genomics have provided an unprecedented ability to measure diverse molecular modalities, but predicting causal regulatory relationships from observational data remains challenging. Here, we leverage pooled genetic screens and single-cell sequencing (Perturb-seq) to systematically identify the targets of signalling regulators in diverse biological contexts. We demonstrate how Perturb-seq is compatible with recent and commercially available advances in combinatorial indexing and next-generation sequencing, and perform more than 1,500 perturbations split across six cell lines and five biological signalling contexts. We introduce an improved computational framework (Mixscale) to address cellular variation in perturbation efficiency, alongside optimized statist

SUBMITTER: Jiang L 

PROVIDER: S-EPMC12083445 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature