Evidence map›Paper›PMID 40011559›Full record

ArticleNature cell biology2025

Decoding heterogeneous single-cell perturbation responses.

Bicna Song, Dingyu Liu, Weiwei Dai, Natalie F McMyn, Qingyang Wang, Dapeng Yang, Adam Krejci, Anatoly Vasilyev, Nicole Untermoser, Anke Loregger and 14 more

Abstract read
In one paragraph

Article in Nature cell biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing 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

16 citing papers in PubMed.

  1. Article
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  13. Article
  14. Fluctuation structure predicts genome-wide perturbation outcomes.bioRxiv : the preprint server for biology · 2025
    Article
  15. Article
  16. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors.

Bicna SongCenter for Genetic Medicine Research, Children's National Hospital, Washington, DC, USA.ORCID 0000-0001-6701-777X
Dingyu LiuDevelopmental Biology Program, Sloan Kettering Institute, New York City, NY, USA.
Weiwei DaiDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Natalie F McMynDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Qingyang WangDepartment of Statistics and Data Science, University of California, Los Angeles, CA, USA.
Dapeng YangDevelopmental Biology Program, Sloan Kettering Institute, New York City, NY, USA.ORCID 0000-0001-8687-4486
Adam KrejciMyllia Biotechnology GmbH, Vienna, Austria.
Anatoly VasilyevMyllia Biotechnology GmbH, Vienna, Austria.
Nicole UntermoserMyllia Biotechnology GmbH, Vienna, Austria.
Anke LoreggerMyllia Biotechnology GmbH, Vienna, Austria.
Dongyuan SongBioinformatics Interdepartmental PhD Program, University of California, Los Angeles, CA, USA.ORCID 0000-0003-1114-1215
Breanna WilliamsDevelopmental Biology Program, Sloan Kettering Institute, New York City, NY, USA.
Bess RosenDevelopmental Biology Program, Sloan Kettering Institute, New York City, NY, USA.
Xiaolong ChengCenter for Genetic Medicine Research, Children's National Hospital, Washington, DC, USA.
Lumen ChaoCenter for Genetic Medicine Research, Children's National Hospital, Washington, DC, USA.
Hanuman T KaleDevelopmental Biology Program, Sloan Kettering Institute, New York City, NY, USA.
Hao ZhangDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Yarui DiaoDepartment of Cell Biology, Duke University Medical Center, Durham, NC, USA.ORCID 0000-0001-5842-4082
Tilmann BürckstümmerMyllia Biotechnology GmbH, Vienna, Austria.
Janet D SilicianoDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Jingyi Jessica LiDepartment of Statistics and Data Science, University of California, Los Angeles, CA, USA.ORCID 0000-0002-9288-5648
Robert F SilicianoDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID 0000-0002-1764-1993
Danwei HuangfuDevelopmental Biology Program, Sloan Kettering Institute, New York City, NY, USA.ORCID 0000-0002-1145-6199
Wei LiCenter for Genetic Medicine Research, Children's National Hospital, Washington, DC, USA. wli2@childrensnational.org.ORCID 0000-0002-2163-7903

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4M
SWG 2: Cure Research Scientific Working GroupP30AI117970 · NIAID · GEORGE WASHINGTON UNIVERSITY · PI Italo Mocchetti · 2015 to 2026
$29.6M
Center for scalable knockout and multimodal phenotyping in genetically diverse human genomesUM1HG012654 · NHGRI · SLOAN-KETTERING INST CAN RESEARCH · PI Danwei Huangfu, LORENZ P. STUDER · 2022 to 2026
$9.1M
Genomic control of gene regulatory networks governing early human lineagedecisionsU01HG012051 · NHGRI · SLOAN-KETTERING INST CAN RESEARCH · PI Michael A Beer, ANNA-KATERINA HADJANTONAKIS · 2021 to 2026
$8.3M
Pharmacology and Molecular Sciences Training Program: Enhancing Inclusivity Through Universal Design for Learning in Graduate CoursesT32GM135083 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI Caren L. Freel Meyers · 2020 to 2026
$3.3M
Integrative genomic and functional genomic studies to connect variant to function for CAD GWAS lociR01HL168174 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Wei Li, EDOARDO MARCORA · 2023 to 2026
$3.1M
Modeling Heterogenous Outcomes in Functional Genetic Screens Using Single-cell Genomics as ReadoutsR01HG010753 · NHGRI · CHILDREN'S RESEARCH INSTITUTE · PI LI, WEI · 2019 to 2023
$2.5M
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
National Science Foundation (NSF) DBI-1846216, DMS-2113754NCI NIH HHS P30 CA008748NHGRI NIH HHS R01 HG010753NHGRI NIH HHS U01 HG012051NHGRI NIH HHS UM1 HG012654NHLBI NIH HHS R01 HL168174NIAID NIH HHS P30 AI117970NIGMS NIH HHS R35 GM140888NIGMS NIH HHS T32 GM135083U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R01HL168174U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI) R01HG010753U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI) UM1HG012654, U01HG012051U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R35GM140888
6 · The paper itself

Abstract

Understanding how cells respond differently to perturbation is crucial in cell biology, but existing methods often fail to accurately quantify and interpret heterogeneous single-cell responses. Here we introduce the perturbation-response score (PS), a method to quantify diverse perturbation responses at a single-cell level. Applied to single-cell perturbation datasets such as Perturb-seq, PS outperforms existing methods in quantifying partial gene perturbations. PS further enables single-cell dosage analysis without needing to titrate perturbations, and identifies 'buffered' and 'sensitive' response patterns of essential genes, depending on whether their moderate perturbations lead to strong downstream effects. PS reveals differential cellular responses on perturbing key genes in contexts such as T cell stimulation, latent HIV-1 expression and pancreatic differentiation. Notably, we identified a previously unknown role for the coiled-coil domain containing 6 (CCDC6) in regulating liver and pancreatic cell fate decisions. PS provides a powerful method for dose-to-function analysis, offering deeper insights from single-cell perturbation data.

Indexed as

Single-Cell AnalysisAnimalsCell DifferentiationHIV-1HumansPancreas

Identifiers

PMID40011559
PMCPMC11906366

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.