Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Май 23, 2025

Transcriptomes provide highly informative molecular phenotypes that, combined with gene perturbation, can connect genotype to phenotype. An ultimate goal is perturb every and measure transcriptome changes, however, this challenging, especially in whole animals. Here, we present 'Worm Perturb-Seq (WPS)', a method that provides high-resolution RNA-sequencing profiles for hundreds of replicate perturbations at time living WPS introduces multiple experimental advances combining strengths Caenhorhabditis elegans genetics multiplexed novel analytical framework, EmpirDE. EmpirDE leverages the unique power large transcriptomic datasets improves statistical rigor by using gene-specific empirical null distributions identify DEGs. We apply 103 nuclear hormone receptors (NHRs) find striking 'pairwise modularity' which pairs NHRs regulate shared target genes. envision be useful not only C. elegans, but broadly other models, including human cells.

Язык: Английский