Evidence map›Paper›PMID 37872410›Full record

ArticleNature biotechnology2024

Scalable genetic screening for regulatory circuits using compressed Perturb-seq.

Douglas Yao, Loic Binan, Jon Bezney, Brooke Simonton, Jahanara Freedman, Chris J Frangieh, Kushal Dey, Kathryn Geiger-Schuller, Basak Eraslan, Alexander Gusev and 2 more

Abstract read
In one paragraph

Article in Nature biotechnology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.

0numbers the graph read from it
0cells of the map it votes in
69citing 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

69 citing papers in PubMed.

  1. Review
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  5. Article
  6. Article
  7. Proteomics-Driven Strategies for Proximity-Inducing Drug Discovery.Angewandte Chemie (International ed. in English) · 2026
    Review
  8. Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. ScalablebioRxiv : the preprint server for biology · 2026
    Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Review
  19. Article
  20. Article

9 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Douglas YaoProgram in Systems, Synthetic, and Quantitative Biology, Harvard University, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-0939-4670
Loic BinanKlarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Jon BezneyKlarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Brooke SimontonKlarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Jahanara FreedmanKlarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Chris J FrangiehKlarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Kushal DeyHarvard T.H. Chan School of Public Health, Boston, MA, USA.ORCID http://orcid.org/0000-0002-3520-2345
Kathryn Geiger-SchullerGenentech, South San Francisco, CA, USA.
Basak EraslanGenentech, South San Francisco, CA, USA.
Alexander GusevKlarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-7980-4620
Aviv RegevKlarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Brian ClearyFaculty of Computing and Data Sciences, Boston University, Boston, MA, USA. bcleary@bu.edu.

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
Training Program in Bioinformatics and Integrative GenomicsT32HG002295 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Peter J Park · 2001 to 2026
$15.8M
Center for Cell CircuitsRM1HG006193 · NHGRI · BROAD INSTITUTE, INC. · PI BLAINEY, PAUL CLARK, HACOHEN, NIR · 2016 to 2020
$14.9M
Methods for Genome-wide Association Studies in Admixed PopulationsR01HG006399 · NHGRI · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI PRICE, ALKES L · 2011 to 2024
$6.3M
Characterizing the evolutionary architecture of complex disease within and across diverse populationsR01HG012133 · NHGRI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI MANCUSO, NICHOLAS · 2021 to 2025
$3.6M
New approaches for leveraging single-cell data to identify disease-critical genes and gene setsR00HG012203 · NHGRI · SLOAN-KETTERING INST CAN RESEARCH · PI DEY, KUSHAL KUMAR · 2023 to 2025
$747k
National Science Foundation (NSF) 1745303NCI NIH HHS P30 CA008748NHGRI NIH HHS R00 HG012203NHGRI NIH HHS R01 HG006399NHGRI NIH HHS R01 HG012133NHGRI NIH HHS RM1 HG006193NHGRI NIH HHS T32 HG002295U.S. Department of Health & Human Services | National Institutes of Health (NIH) HG006399U.S. Department of Health & Human Services | National Institutes of Health (NIH) R00HG012203U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI) RM1HG006193
6 · The paper itself

Abstract

Pooled CRISPR screens with single-cell RNA sequencing readout (Perturb-seq) have emerged as a key technique in functional genomics, but they are limited in scale by cost and combinatorial complexity. In this study, we modified the design of Perturb-seq by incorporating algorithms applied to random, low-dimensional observations. Compressed Perturb-seq measures multiple random perturbations per cell or multiple cells per droplet and computationally decompresses these measurements by leveraging the sparse structure of regulatory circuits. Applied to 598 genes in the immune response to bacterial lipopolysaccharide, compressed Perturb-seq achieves the same accuracy as conventional Perturb-seq with an order of magnitude cost reduction and greater power to learn genetic interactions. We identified known and novel regulators of immune responses and uncovered evolutionarily constrained genes with downstream targets enriched for immune disease heritability, including many missed by existing genome-wide association studies. Our framework enables new scales of interrogation for a foundational method in functional genomics.

Indexed as

AlgorithmsGene Regulatory NetworksCRISPR-Cas SystemsGenetic TestingGenome-Wide Association StudyGenomicsHumansSequence Analysis, RNASingle-Cell Analysis

Identifiers

PMID37872410
PMCPMC11035494

What OpenQuestion holds

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Registered trials

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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.