Evidence map›Paper›PMID 31395745›Full record

ArticleScience (New York, N.Y.)2019

Exploring genetic interaction manifolds constructed from rich single-cell phenotypes.

Thomas M Norman, Max A Horlbeck, Joseph M Replogle, Alex Y Ge, Albert Xu, Marco Jost, Luke A Gilbert, Jonathan S Weissman

Abstract read
In one paragraph

Article in Science (New York, N.Y.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 201 papers.

0numbers the graph read from it
0cells of the map it votes in
201citing 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

201 citing papers in PubMed.

  1. Latent causal diffusions for single-cell perturbation modeling.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  19. ScalablebioRxiv : the preprint server for biology · 2026
    Article
  20. Computational modelling of cell identity.The Biochemical journal · 2026
    Review

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Thomas M Norman *Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA. thomas.norman@ucsf.edu luke.gilbert@ucsf.edu jonathan.weissman@ucsf.edu.ORCID 0000-0002-3755-4379
Max A Horlbeck *Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA.ORCID 0000-0002-3875-871X
Joseph M ReplogleDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA.ORCID 0000-0003-1832-919X
Alex Y GeDepartment of Urology, University of California, San Francisco, CA 94158, USA.ORCID 0000-0002-6595-1822
Albert XuDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA.
Marco JostDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA.ORCID 0000-0002-1369-4908
Luke A GilbertDepartment of Urology, University of California, San Francisco, CA 94158, USA. thomas.norman@ucsf.edu luke.gilbert@ucsf.edu jonathan.weissman@ucsf.edu.ORCID 0000-0001-5854-0825
Jonathan S WeissmanDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA. thomas.norman@ucsf.edu luke.gilbert@ucsf.edu jonathan.weissman@ucsf.edu.ORCID 0000-0003-2445-670X

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007618 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ANDERSON, MARK S · 1985 to 2020
$29.6M
Center for Genomic Editing and Recording: Development and Application of Next-Generation Genome and Epigenome Editing Methods to Advance the Study and Treatment of Human DiseaseRM1HG009490 · NHGRI · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI Brittany S. Adamson, Martin Joseph Ankrah Aryee · 2017 to 2026
$22.7M
PROJECT 3P50GM102706 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI CATE, JAMIE H · 2012 to 2016
$9.5M
The Cancer Target Discovery and Development Network at UCSFU01CA217882 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BANDYOPADHYAY, SOURAV, BIVONA, TREVER G · 2017 to 2021
$5.2M
Bay Area Cancer Target Discovery and Development NetworkU01CA168370 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MCCORMICK, FRANK PATRICK, MCMANUS, MICHAEL T · 2012 to 2016
$3.9M
Integrative Program in Complex Biological System (ipCBS)T32EB009383 · NIBIB · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MARSHALL, WALLACE, WEINER, ORION D · 2009 to 2022
$3.2M
Harnessing CRISPR for Targeted and Inducible Epigenomic ReprogrammingR01DA036858 · NIDA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LIM, WENDELL A, QI, LEI STANLEY · 2013 to 2017
$2.9M
A GENETIC INTERACTION MAP OF THE HUMAN NUCLEUSDP2CA239597 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GILBERT, LUKE · 2018 to 2018
$2.4M
A functional genomics approach to determine the mechanism of cellular response to new anti-cancer R00CA204602 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GILBERT, LUKE · 2017 to 2019
$747k
Systematic Genome-Wide Characterization of Iron HomeostasisF32GM116331 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JOST, MARCO · 2015 to 2017
$162k
A functional genomics approach to determine the mechanism of cellular response to new anti-cancer drugsK99CA204602 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GILBERT, LUKE · 2016 to 2016
$139k
Howard Hughes Medical InstituteNCI NIH HHS DP2 CA239597NCI NIH HHS K99 CA204602NCI NIH HHS R00 CA204602NCI NIH HHS U01 CA168370NCI NIH HHS U01 CA217882NHGRI NIH HHS RM1 HG009490NIBIB NIH HHS T32 EB009383NIDA NIH HHS R01 DA036858NIGMS NIH HHS F32 GM116331NIGMS NIH HHS P50 GM102706NIGMS NIH HHS T32 GM007618
6 · The paper itself

Abstract

How cellular and organismal complexity emerges from combinatorial expression of genes is a central question in biology. High-content phenotyping approaches such as Perturb-seq (single-cell RNA-sequencing pooled CRISPR screens) present an opportunity for exploring such genetic interactions (GIs) at scale. Here, we present an analytical framework for interpreting high-dimensional landscapes of cell states (manifolds) constructed from transcriptional phenotypes. We applied this approach to Perturb-seq profiling of strong GIs mined from a growth-based, gain-of-function GI map. Exploration of this manifold enabled ordering of regulatory pathways, principled classification of GIs (e.g., identifying suppressors), and mechanistic elucidation of synergistic interactions, including an unexpected synergy between

Indexed as

Epistasis, GeneticApoptosisCalcium-Binding ProteinsCalponinsCell Cycle CheckpointsCell Line, TumorCRISPR-Cas SystemsErythroid CellsErythropoiesisFemaleGene Expression ProfilingGranulocytesHumansMicrofilament ProteinsProto-Oncogene Proteins c-cblSequence Analysis, RNACalcium-Binding ProteinsCalponinsCBL protein, humanMicrofilament ProteinsProto-Oncogene Proteins c-cbl

Identifiers

PMID31395745
PMCPMC6746554

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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.