Evidence map›Paper›PMID 38278156›Full record

ArticleCell genomics2024

Multiplex single-cell chemical genomics reveals the kinase dependence of the response to targeted therapy.

José L McFaline-Figueroa, Sanjay Srivatsan, Andrew J Hill, Molly Gasperini, Dana L Jackson, Lauren Saunders, Silvia Domcke, Samuel G Regalado, Paul Lazarchuck, Sarai Alvarez and 3 more

Open access · goldAbstract read
In one paragraph

Article in Cell genomics, 2024. 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
3.7field-weighted citation impact, top 6% of its field
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, 16 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 3 institutions in 1 country.

José L McFaline-FigueroaDepartment of Biomedical Engineering, Columbia University, New York, NY, USA; Department of Genome Sciences, University of Washington, Seattle, WA, USA. Electronic address: jm5200@columbia.edu.
Sanjay SrivatsanDepartment of Genome Sciences, University of Washington, Seattle, WA, USA; Medical Scientist Training Program, University of Washington, Seattle, WA, USA.
Andrew J HillDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.
Molly GasperiniDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.
Dana L JacksonDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.
Lauren SaundersDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.
Silvia DomckeDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.
Samuel G RegaladoDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.
Paul LazarchuckDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.
Sarai AlvarezDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.
Raymond J MonnatDepartment of Genome Sciences, University of Washington, Seattle, WA, USA; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA.
Jay ShendureDepartment of Genome Sciences, University of Washington, Seattle, WA, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA; Allen Discovery Center for Cell Lineage Tracing, Seattle, WA, USA; Howard Hughes Medical Institute, University of Washington, Seattle, WA, USA; Brotman Baty Institute for Precision Medicine, Seattle, WA, USA.
Cole TrapnellDepartment of Genome Sciences, University of Washington, Seattle, WA, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA; Allen Discovery Center for Cell Lineage Tracing, Seattle, WA, USA; Brotman Baty Institute for Precision Medicine, Seattle, WA, USA. Electronic address: coletrap@uw.edu.
University of Washington · USAllen Institute · USColumbia University · US

Funding

INTERDISCIPLINARY TRAINING IN GENOMIC SCIENCEST32HG000035 · NHGRI · UNIVERSITY OF WASHINGTON · PI Bruce Colston Trapnell · 1995 to 2026
$24.2M
CARDIOVASCULAR RESEARCH TRAINING PROGRAMT32HL007828 · NHLBI · UNIVERSITY OF WASHINGTON · PI Francis Kim, Farid Moussavi-Harami · 1997 to 2026
$10.2M
Versatile, exponentially scalable methods for single cell molecular profilingR01HG010632 · NHGRI · UNIVERSITY OF WASHINGTON · PI Jay Ashok Shendure, Bruce Colston Trapnell · 2019 to 2026
$5.9M
Interpreting Genetic Variants of Uncertain SignificanceDP1HG007811 · NHGRI · UNIVERSITY OF WASHINGTON · PI SHENDURE, JAY ASHOK · 2013 to 2017
$3.8M
Massively Parallel Contiguity MappingR01HG006283 · NHGRI · UNIVERSITY OF WASHINGTON · PI SHENDURE, JAY ASHOK · 2011 to 2016
$3.4M
Defining gene-by-environment interactions using multiplex single-cell genomicsR35HG011941 · NHGRI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI MCFALINE-FIGUEROA, JOSE LUIS · 2021 to 2025
$2.5M
Charting the regulatory topography of the cell differentiation landscape with single-cell RNA-Seq.DP2HD088158 · NICHD · UNIVERSITY OF WASHINGTON · PI TRAPNELL, BRUCE COLSTON · 2015 to 2015
$2.3M
NHGRI NIH HHS DP1 HG007811NHGRI NIH HHS R01 HG006283NHGRI NIH HHS R01 HG010632NHGRI NIH HHS R35 HG011941NHGRI NIH HHS T32 HG000035NHLBI NIH HHS T32 HL007828NICHD NIH HHS DP2 HD088158
6 · The paper itself

Abstract

Chemical genetic screens are a powerful tool for exploring how cancer cells' response to drugs is shaped by their mutations, yet they lack a molecular view of the contribution of individual genes to the response to exposure. Here, we present sci-Plex-Gene-by-Environment (sci-Plex-GxE), a platform for combined single-cell genetic and chemical screening at scale. We highlight the advantages of large-scale, unbiased screening by defining the contribution of each of 522 human kinases to the response of glioblastoma to different drugs designed to abrogate signaling from the receptor tyrosine kinase pathway. In total, we probed 14,121 gene-by-environment combinations across 1,052,205 single-cell transcriptomes. We identify an expression signature characteristic of compensatory adaptive signaling regulated in a MEK/MAPK-dependent manner. Further analyses aimed at preventing adaptation revealed promising combination therapies, including dual MEK and CDC7/CDK9 or nuclear factor κB (NF-κB) inhibitors, as potent means of preventing transcriptional adaptation of glioblastoma to targeted therapy.

Indexed as

GlioblastomaCell Cycle ProteinsGenomicsHumansMitogen-Activated Protein Kinase KinasesProtein Serine-Threonine KinasesReceptor Protein-Tyrosine KinasesSignal TransductionCDC7 protein, humanCell Cycle ProteinsMitogen-Activated Protein Kinase KinasesProtein Serine-Threonine KinasesReceptor Protein-Tyrosine Kinasesadaptive resistancechemical geneticschemical genomicscombined single-cell genetic and chemical screensgene by environment interactionsglioblastomakinase-directed therapyreceptor tyrosine kinase signalingsingle-cell chemical transcriptomicssingle-cell CRISPR screens

Identifiers

PMID38278156
PMCPMC10879025
OpenAlexW4391234592

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.