Worm Perturb-Seq: massively parallel whole-animal RNAi and RNA-seq DOI Creative Commons
Hefei Zhang, Xuhang Li, Dongyuan Song

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: May 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.

Language: Английский

Systems-level design principles of metabolic rewiring in an animal DOI
Xuhang Li, Hefei Zhang,

Thomas Hodder

et al.

Nature, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 26, 2025

Language: Английский

Citations

1
Worm Perturb-Seq: massively parallel whole-animal RNAi and RNA-seq DOI Creative Commons
Hefei Zhang, Xuhang Li, Dongyuan Song

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: May 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.

Language: Английский

Citations

0