Evidence map›Paper›PMID 35411116›Full record

ArticleNature biotechnology2022

High-throughput functional evaluation of human cancer-associated mutations using base editors.

Younggwang Kim, Seungho Lee, Soohyuk Cho, Jinman Park, Dongwoo Chae, Taeyoung Park, John D Minna, Hyongbum Henry Kim

Abstract 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 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing 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

45 citing papers in PubMed.

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  5. A proteome-wide dependency map of protein interaction motifs.Nature structural & molecular biology · 2026
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  7. Review
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  12. Genetic mechanisms of resistance to targeted KRAS inhibition.bioRxiv : the preprint server for biology · 2025
    Article
  13. Review
  14. Article
  15. MultiplexedbioRxiv : the preprint server for biology · 2025
    Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Younggwang Kim *Department of Pharmacology, Yonsei University College of Medicine, Seoul, Republic of Korea.
Seungho Lee *Department of Pharmacology, Yonsei University College of Medicine, Seoul, Republic of Korea.
Soohyuk ChoDepartment of Pharmacology, Yonsei University College of Medicine, Seoul, Republic of Korea.
Jinman ParkDepartment of Pharmacology, Yonsei University College of Medicine, Seoul, Republic of Korea.
Dongwoo ChaeDepartment of Pharmacology, Yonsei University College of Medicine, Seoul, Republic of Korea.
Taeyoung ParkDepartment of Applied Statistics, Yonsei University, Seoul, Republic of Korea.
John D MinnaHamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Hyongbum Henry KimDepartment of Pharmacology, Yonsei University College of Medicine, Seoul, Republic of Korea. hkim1@yuhs.ac.ORCID http://orcid.org/0000-0002-4693-738X

Funding

UNIVERSITY OF TEXAS--SPORE IN LUNG CANCERP50CA070907 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI GIBBONS, DON LYNN · 1996 to 2024
$57.4M
NCI NIH HHS P50 CA070907
6 · The paper itself

Abstract

Comprehensive phenotypic characterization of the many mutations found in cancer tissues is one of the biggest challenges in cancer genomics. In this study, we evaluated the functional effects of 29,060 cancer-related transition mutations that result in protein variants on the survival and proliferation of non-tumorigenic lung cells using cytosine and adenine base editors and single guide RNA (sgRNA) libraries. By monitoring base editing efficiencies and outcomes using surrogate target sequences paired with sgRNA-encoding sequences on the lentiviral delivery construct, we identified sgRNAs that induced a single primary protein variant per sgRNA, enabling linking those mutations to the cellular phenotypes caused by base editing. The functions of the vast majority of the protein variants (28,458 variants, 98%) were classified as neutral or likely neutral; only 18 (0.06%) and 157 (0.5%) variants caused outgrowing and likely outgrowing phenotypes, respectively. We expect that our approach can be extended to more variants of unknown significance and other tumor types.

Indexed as

Gene EditingNeoplasmsCRISPR-Cas SystemsHumansMutationRNA, Guide, CRISPR-Cas SystemsRNA, Guide, CRISPR-Cas Systems

Identifiers

PMID35411116
PMCPMC10243181

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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.