Evidence map›Paper›PMID 32855387›Full record

ArticleNature communications2020

Multiplexed single-cell transcriptional response profiling to define cancer vulnerabilities and therapeutic mechanism of action.

James M McFarland, Brenton R Paolella, Allison Warren, Kathryn Geiger-Schuller, Tsukasa Shibue, Michael Rothberg, Olena Kuksenko, William N Colgan, Andrew Jones, Emily Chambers and 12 more

Abstract read
In one paragraph

Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
92citing papers in PubMed, 1 pooled it
–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

92 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  10. Contrastive Dimension Reduction: A Systematic Review.Wiley interdisciplinary reviews. Computational statistics · 2026
    Article
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  14. Review
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32 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

22 authors.

James M McFarland *Broad Institute of MIT and Harvard, Cambridge, 021242, MA, USA.ORCID http://orcid.org/0000-0001-9978-480X
Brenton R Paolella *Broad Institute of MIT and Harvard, Cambridge, 021242, MA, USA.ORCID http://orcid.org/0000-0003-3394-828X
Allison WarrenBroad Institute of MIT and Harvard, Cambridge, 021242, MA, USA.
Kathryn Geiger-SchullerBroad Institute of MIT and Harvard, Cambridge, 021242, MA, USA.ORCID http://orcid.org/0000-0002-6705-0681
Tsukasa ShibueBroad Institute of MIT and Harvard, Cambridge, 021242, MA, USA.
Michael RothbergBroad Institute of MIT and Harvard, Cambridge, 021242, MA, USA.
Olena KuksenkoBroad Institute of MIT and Harvard, Cambridge, 021242, MA, USA.
William N ColganBroad Institute of MIT and Harvard, Cambridge, 021242, MA, USA.ORCID http://orcid.org/0000-0002-8328-4672
Andrew JonesBroad Institute of MIT and Harvard, Cambridge, 021242, MA, USA.
Emily ChambersBroad Institute of MIT and Harvard, Cambridge, 021242, MA, USA.
Danielle DionneBroad Institute of MIT and Harvard, Cambridge, 021242, MA, USA.
Samantha BenderBroad Institute of MIT and Harvard, Cambridge, 021242, MA, USA.
Brian M WolpinHarvard Medical School, Boston, 02115, MA, USA.
Mahmoud GhandiBroad Institute of MIT and Harvard, Cambridge, 021242, MA, USA.ORCID http://orcid.org/0000-0003-1897-2265
Itay TiroshKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, 021242, MA, USA.
Orit Rozenblatt-RosenBroad Institute of MIT and Harvard, Cambridge, 021242, MA, USA.
Jennifer A RothBroad Institute of MIT and Harvard, Cambridge, 021242, MA, USA.
Todd R GolubBroad Institute of MIT and Harvard, Cambridge, 021242, MA, USA.ORCID http://orcid.org/0000-0003-0113-2403
Aviv RegevBroad Institute of MIT and Harvard, Cambridge, 021242, MA, USA.ORCID http://orcid.org/0000-0003-3293-3158
Andrew J AguirreBroad Institute of MIT and Harvard, Cambridge, 021242, MA, USA. andrew_aguirre@dfci.harvard.edu.ORCID http://orcid.org/0000-0002-0701-6203
Francisca VazquezBroad Institute of MIT and Harvard, Cambridge, 021242, MA, USA. vazquez@broadinstitute.org.ORCID http://orcid.org/0000-0002-2857-4685
Aviad TsherniakBroad Institute of MIT and Harvard, Cambridge, 021242, MA, USA. aviad@broadinstitute.org.ORCID http://orcid.org/0000-0002-3797-1877

Funding

Tissue and Pathology ResourcesP50CA127003 · NCI · DANA-FARBER CANCER INST · PI EL-BARDEESY, NABEEL, SELLERS, WILLIAM R · 2007 to 2023
$33.2M
Systematic interrogation of the pancreatic cancer microenvironment in patient-derived specimensU01CA224146 · NCI · DANA-FARBER CANCER INST · PI HAHN, WILLIAM C. · 2017 to 2021
$3.0M
Development and implementation of multiplex methods to understand the biology and heterogeneity of patient-derived cancer modelsU01CA250549 · NCI · DANA-FARBER CANCER INST · PI HAHN, WILLIAM C. · 2020 to 2022
$2.9M
Functional interrogation of epigenetic vulnerabilities in KRAS-mutant pancreatic cancerK08CA218420 · NCI · DANA-FARBER CANCER INST · PI AGUIRRE, ANDREW JAMES · 2017 to 2021
$886k
Howard Hughes Medical InstituteNCI NIH HHS K08 CA218420NCI NIH HHS P50 CA127003NCI NIH HHS U01 CA224146NCI NIH HHS U01 CA250549
6 · The paper itself

Abstract

Assays to study cancer cell responses to pharmacologic or genetic perturbations are typically restricted to using simple phenotypic readouts such as proliferation rate. Information-rich assays, such as gene-expression profiling, have generally not permitted efficient profiling of a given perturbation across multiple cellular contexts. Here, we develop MIX-Seq, a method for multiplexed transcriptional profiling of post-perturbation responses across a mixture of samples with single-cell resolution, using SNP-based computational demultiplexing of single-cell RNA-sequencing data. We show that MIX-Seq can be used to profile responses to chemical or genetic perturbations across pools of 100 or more cancer cell lines. We combine it with Cell Hashing to further multiplex additional experimental conditions, such as post-treatment time points or drug doses. Analyzing the high-content readout of scRNA-seq reveals both shared and context-specific transcriptional response components that can identify drug mechanism of action and enable prediction of long-term cell viability from short-term transcriptional responses to treatment.

Indexed as

Antineoplastic AgentsBase SequenceCell Line, TumorCell SurvivalGene Expression ProfilingGene Expression Regulation, NeoplasticHumansModels, StatisticalNeoplasmsPolymorphism, Single NucleotidePyridonesPyrimidinonesSingle-Cell AnalysisAntineoplastic AgentsPyridonesPyrimidinonestrametinib

Identifiers

PMID32855387
PMCPMC7453022

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.