Evidence map›Paper›PMID 38134886›Full record

ArticleMolecular cell2023

High-throughput PRIME-editing screens identify functional DNA variants in the human genome.

Xingjie Ren, Han Yang, Jovia L Nierenberg, Yifan Sun, Jiawen Chen, Cooper Beaman, Thu Pham, Mai Nobuhara, Maya Asami Takagi, Vivek Narayan and 3 more

Open access · hybridAbstract read
In one paragraph

Article in Molecular cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed, 1 pooled it
9.7field-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

47 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.

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  18. Genetic regulation of the estrogen receptor and inherited predisposition to breast cancer.Proceedings of the National Academy of Sciences of the United States of America · 2025
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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.

Xingjie RenInstitute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
Han YangInstitute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
Jovia L NierenbergDepartment of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA.
Yifan SunInstitute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
Jiawen ChenDepartment of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Cooper BeamanInstitute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
Thu PhamPharmaceutical Sciences and Pharmacogenomics Graduate Program, University of California, San Francisco, San Francisco, CA, USA.
Mai NobuharaPharmaceutical Sciences and Pharmacogenomics Graduate Program, University of California, San Francisco, San Francisco, CA, USA.
Maya Asami TakagiInstitute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
Vivek NarayanInstitute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
Yun LiDepartment of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Genetics, University of North Carolina, Chapel Hill, NC, USA; Department of Computer Science, University of North Carolina, Chapel Hill, NC, USA.
Elad ZivInstitute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA; Division of General Internal Medicine, Department of Medicine, and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
Yin ShenInstitute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA, USA; Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA. Electronic address: yin.shen@ucsf.edu.
University of California, San Francisco · USUniversity of North Carolina at Chapel Hill · USUCSF Helen Diller Family Comprehensive Cancer Center · US

Funding

High throughput CRISPR-mediated functional validation of regulatory elementsUM1HG009402 · NHGRI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI REN, BING, SHEN, YIN · 2017 to 2021
$8.4M
Polygenic risk scores for cardiometabolic disorders: the role of blood cells immune response and evolutionary adaptationU01HG011720 · NHGRI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Yun Li, ALEXANDER P REINER · 2021 to 2026
$5.4M
Functional characterization of Alzheimer's disease associated genetic variantsR01AG057497 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GAN, LI, SHEN, YIN · 2017 to 2021
$4.2M
Charting the 3D epigenome in human brain development and diseasesU01DA052713 · NIDA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KRIEGSTEIN, ARNOLD, SHEN, YIN · 2020 to 2024
$3.4M
Transcriptional regulation of BEST1 in retina pigment epithelium.R01EY027789 · NEI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SHEN, YIN · 2017 to 2021
$2.1M
Illumina NovaSeq 6000 Sequencing SystemS10OD028511 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHOW, ERIC D · 2020 to 2020
$583k
NEI NIH HHS R01 EY027789NHGRI NIH HHS U01 HG011720NHGRI NIH HHS UM1 HG009402NIA NIH HHS R01 AG057497NIDA NIH HHS U01 DA052713NIH HHS S10 OD028511
6 · The paper itself

Abstract

Despite tremendous progress in detecting DNA variants associated with human disease, interpreting their functional impact in a high-throughput and single-base resolution manner remains challenging. Here, we develop a pooled prime-editing screen method, PRIME, that can be applied to characterize thousands of coding and non-coding variants in a single experiment with high reproducibility. To showcase its applications, we first identified essential nucleotides for a 716 bp MYC enhancer via PRIME-mediated single-base resolution analysis. Next, we applied PRIME to functionally characterize 1,304 genome-wide association study (GWAS)-identified non-coding variants associated with breast cancer and 3,699 variants from ClinVar. We discovered that 103 non-coding variants and 156 variants of uncertain significance are functional via affecting cell fitness. Collectively, we demonstrate that PRIME is capable of characterizing genetic variants at single-base resolution and scale, advancing accurate genome annotation for disease risk prediction, diagnosis, and therapeutic target identification.

Indexed as

Genome, HumanGenome-Wide Association StudyCRISPR-Cas SystemsDNAGene EditingHumansRegulatory Sequences, Nucleic AcidReproducibility of ResultsDNAdisease variantsenhancerhigh-throughput screensprime editingsingle-base resolution

Identifiers

PMID38134886
PMCPMC10766087
OpenAlexW4390063959

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.