Evidence map›Paper›PMID 35165384›Full record

ArticleNature biotechnology2022

Base editing sensor libraries for high-throughput engineering and functional analysis of cancer-associated single nucleotide variants.

Francisco J Sánchez-Rivera, Bianca J Diaz, Edward R Kastenhuber, Henri Schmidt, Alyna Katti, Margaret Kennedy, Vincent Tem, Yu-Jui Ho, Josef Leibold, Stella V Paffenholz and 11 more

Open access · greenAbstract read
In one paragraph

Article in Nature biotechnology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.

0numbers the graph read from it
0cells of the map it votes in
83citing papers in PubMed
10.0field-weighted citation impact, top 1% 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

83 citing papers in PubMed, 122 citations in OpenAlex.

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  14. A SLiM view of the human proteome.Nature structural & molecular biology · 2026
    Article
  15. A proteome-wide dependency map of protein interaction motifs.Nature structural & molecular biology · 2026
    Article
  16. Article
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  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors at 2 institutions in 2 countries.

Francisco J Sánchez-Rivera *Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Bianca J Diaz *Sandra and Edward Meyer Cancer Center, Department of Medicine, Weill Cornell Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0002-5309-1300
Edward R Kastenhuber *Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-1872-212X
Henri SchmidtComputational Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-0132-3472
Alyna KattiSandra and Edward Meyer Cancer Center, Department of Medicine, Weill Cornell Medicine, New York, NY, USA.
Margaret KennedyCancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID http://orcid.org/0000-0001-9106-1906
Vincent TemCancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Yu-Jui HoCancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Josef LeiboldCancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Stella V PaffenholzCancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Francisco M BarrigaCancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-0996-7707
Kevan ChuSandra and Edward Meyer Cancer Center, Department of Medicine, Weill Cornell Medicine, New York, NY, USA.
Sukanya GoswamiSandra and Edward Meyer Cancer Center, Department of Medicine, Weill Cornell Medicine, New York, NY, USA.
Alexandra N WuestCancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Janelle M SimonCancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Kaloyan M TsanovCancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Debyani ChakravartyKravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Hongxin ZhangKravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Christina S LeslieComputational Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-4571-5910
Scott W LoweCancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-5284-9650
Lukas E DowSandra and Edward Meyer Cancer Center, Department of Medicine, Weill Cornell Medicine, New York, NY, USA. lud2005@med.cornell.edu.ORCID http://orcid.org/0000-0001-7048-1418
Memorial Sloan Kettering Cancer Center · USCornell University · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
VIRAL TRANSACTIVATIONP01CA013106 · NCI · COLD SPRING HARBOR LABORATORY · PI SCOTT KEITH LYONS · 1985 to 2026
$116.8M
Scientific ReagentsP01CA087497 · NCI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI PRIVES, CAROL · 2000 to 2021
$35.4M
The Role of Focal Oncogene Amplifications in Lung CancerP01CA129243 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI Piro Lito · 2007 to 2026
$31.2M
Role of Phosphoinositides and Protein Kinases in the control of Cancer MetabolismR35CA197588 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI LEWIS C. CANTLEY · 2016 to 2026
$10.2M
In Vivo Base Editing for Precision Oncology ModelsR01CA229773 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI DOW, LUKAS EDWARD · 2019 to 2023
$3.1M
Translational Research in Oncology Training ProgramT32CA160001 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI SAWYERS, CHARLES L. · 2011 to 2020
$2.0M
Interrogating the role of mutant KRAS allelic imbalance and co-mutated genes in targeted therapy response of NSCLCF31CA261061 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI DIAZ, BIANCA · 2021 to 2024
$189k
Intratumoral Heterogeneity and Tumor Evolution in LymphomaF31CA192835 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI KASTENHUBER, EDWARD R · 2015 to 2018
$157k
Sensitizing Colorectal Cancer to Checkpoint Inhibitors by WNT Pathway SuppressionF31CA247351 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI KATTI, ALYNA · 2020 to 2022
$127k
Howard Hughes Medical InstituteNCI NIH HHS F31 CA192835NCI NIH HHS F31 CA247351NCI NIH HHS F31 CA261061NCI NIH HHS P01 CA013106NCI NIH HHS P01 CA087497NCI NIH HHS P01 CA129243NCI NIH HHS P30 CA008748NCI NIH HHS R01 CA229773NCI NIH HHS R35 CA197588NCI NIH HHS T32 CA160001
6 · The paper itself

Abstract

Base editing can be applied to characterize single nucleotide variants of unknown function, yet defining effective combinations of single guide RNAs (sgRNAs) and base editors remains challenging. Here, we describe modular base-editing-activity 'sensors' that link sgRNAs and cognate target sites in cis and use them to systematically measure the editing efficiency and precision of thousands of sgRNAs paired with functionally distinct base editors. By quantifying sensor editing across >200,000 editor-sgRNA combinations, we provide a comprehensive resource of sgRNAs for introducing and interrogating cancer-associated single nucleotide variants in multiple model systems. We demonstrate that sensor-validated tools streamline production of in vivo cancer models and that integrating sensor modules in pooled sgRNA libraries can aid interpretation of high-throughput base editing screens. Using this approach, we identify several previously uncharacterized mutant TP53 alleles as drivers of cancer cell proliferation and in vivo tumor development. We anticipate that the framework described here will facilitate the functional interrogation of cancer variants in cell and animal models.

Indexed as

Gene EditingNeoplasmsAnimalsCRISPR-Cas SystemsNucleotidesRNA, Guide, CRISPR-Cas SystemsNucleotidesRNA, Guide, CRISPR-Cas Systems

Identifiers

PMID35165384
PMCPMC9232935
OpenAlexW4213232054

What OpenQuestion holds

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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.