Evidence map›Paper›PMID 41087678›Full record

ArticleNature genetics2025

Activity-based selection for enhanced base editor mutational scanning.

Eleanor G Kaplan, Ryan J Steger, Spencer T Shah, Laura M Drepanos, Audrey L Griffith, Ganna Reint, John G Doench

Abstract read
PubMed Publisher
In one paragraph

Article in Nature genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Review
  5. Article
  6. Computational modeling of human genetic variants in mice.bioRxiv : the preprint server for biology · 2025
    Article
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

7 authors.

Eleanor G Kaplan *Genetic Perturbation Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Ryan J Steger *Genetic Perturbation Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Spencer T ShahGenetic Perturbation Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0009-0002-9082-3969
Laura M DrepanosGenetic Perturbation Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0009-0001-5807-1923
Audrey L GriffithGenetic Perturbation Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-5552-2939
Ganna ReintGenetic Perturbation Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
John G DoenchGenetic Perturbation Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA. jdoench@broadinstitute.org.ORCID http://orcid.org/0000-0002-3707-9889

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Base editing is a CRISPR-based technology that enables high-throughput, nucleotide-level functional interrogation of the genome that is essential for understanding the genetic basis of human disease and informing therapeutic development. Base editing screens have emerged as a powerful experimental approach, yet significant cell-to-cell variability in editing efficiency introduces noise that may obscure meaningful results. Here we develop a co-selection method that enriches for cells with high base editing activity, substantially increasing editing efficiency at a target locus. We evaluate this activity-based selection method against a traditional screening approach by tiling guide RNAs across TP53, demonstrating its enhanced capacity to pinpoint specific mutations and protein regions of functional importance. We anticipate that this modular selection method will enhance the resolution of base editing screens across many applications.

Indexed as

CRISPR-Cas SystemsGene EditingMutationHumansRNA, Guide, CRISPR-Cas SystemsTumor Suppressor Protein p53RNA, Guide, CRISPR-Cas SystemsTP53 protein, humanTumor Suppressor Protein p53

Identifiers

PMID41087678

What OpenQuestion holds

Textmetadata
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.