Evidence map›Paper›PMID 40404656›Full record

ArticleNature communications2025

Worm Perturb-Seq: massively parallel whole-animal RNAi and RNA-seq.

Hefei Zhang, Xuhang Li, Dongyuan Song, Onur Yukselen, Shivani Nanda, Alper Kucukural, Jingyi Jessica Li, Manuel Garber, Albertha J M Walhout

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Hefei Zhang *Department of Systems Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA.ORCID http://orcid.org/0000-0002-5187-7166
Xuhang Li *Department of Systems Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA.ORCID http://orcid.org/0000-0001-6071-9605
Dongyuan SongBioinformatics Interdepartmental Ph.D. Program, University of California, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0003-1114-1215
Onur YukselenVia Scientific Inc., Cambridge, MA, USA.
Shivani NandaDepartment of Systems Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA.ORCID http://orcid.org/0000-0001-6358-2392
Alper KucukuralVia Scientific Inc., Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-9983-394X
Jingyi Jessica LiBioinformatics Interdepartmental Ph.D. Program, University of California, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0002-9288-5648
Manuel GarberDepartment of Genomics and Computational Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA. manuel.garber@umassmed.edu.ORCID http://orcid.org/0000-0001-8732-1293
Albertha J M WalhoutDepartment of Systems Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA. marian.walhout@umassmed.edu.ORCID http://orcid.org/0000-0001-5587-3608

Funding

Transcription networks in C elegans organogenesisR01DK068429 · NIDDK · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI A. J. Marian Walhout · 2005 to 2026
$10.9M
Gene regulatory and metabolic network structure, function and evolutionR35GM122502 · NIGMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI A. J. Marian Walhout · 2017 to 2026
$8.3M
Predictive Modeling of the Functional and Phenotypic Impacts of Genetic VariantsU01HG012064 · NHGRI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI Manuel Garber, XIHONG LIN · 2021 to 2026
$4.0M
Statistical Methods for Elucidating Regulatory Mechanisms and Functional Impacts of Transcriptome Variation at Population and Single-Cell ScalesR35GM140888 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LI, JINGYI JESSICA · 2021 to 2025
$2.0M
Gene Regulatory Networks in Development and PhysiologyR56DK068429 · NIDDK · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI WALHOUT, A. J. MARIAN · 2018 to 2018
$671k
NHGRI NIH HHS U01 HG012064NIDDK NIH HHS R01 DK068429NIDDK NIH HHS R56 DK068429NIGMS NIH HHS R35 GM122502NIGMS NIH HHS R35 GM140888U.S. Department of Health & Human Services | National Institutes of Health (NIH) DK068429U.S. Department of Health & Human Services | National Institutes of Health (NIH) GM122502U.S. Department of Health & Human Services | National Institutes of Health (NIH) GM140888U.S. Department of Health & Human Services | National Institutes of Health (NIH) HG012064
6 · The paper itself

Abstract

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

Indexed as

Caenorhabditis elegansRNA InterferenceRNA-SeqSequence Analysis, RNAAnimalsCaenorhabditis elegans ProteinsGene Expression ProfilingHigh-Throughput Nucleotide SequencingHumansReceptors, Cytoplasmic and NuclearTranscriptomeCaenorhabditis elegans ProteinsReceptors, Cytoplasmic and Nuclear

Identifiers

PMID40404656
PMCPMC12098853

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.