Evidence map›Paper›PMID 35286377›Full record

ArticleNucleic acids research2022

Predicting base editing outcomes using position-specific sequence determinants.

Ananth Pallaseni, Elin Madli Peets, Jonas Koeppel, Juliane Weller, Thomas Vanderstichele, Uyen Linh Ho, Luca Crepaldi, Jolanda van Leeuwen, Felicity Allen, Leopold Parts

Abstract read
In one paragraph

Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing 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

36 citing papers in PubMed.

  1. Review
  2. Review
  3. Engineered Transformer Base Editor with Enhanced Editing Efficiency.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. From Code to Life: The AI-Driven Revolution in Genome Editing.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Review
  14. Article
  15. Review
  16. Article
  17. Article
  18. Efforts to Downsize Base Editors for Clinical Applications.International journal of molecular sciences · 2025
    Review
  19. Article
  20. Review
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

10 authors.

Ananth PallaseniWellcome Sanger Institute, Hinxton, UK.ORCID 0000-0002-4840-195X
Elin Madli PeetsWellcome Sanger Institute, Hinxton, UK.
Jonas KoeppelWellcome Sanger Institute, Hinxton, UK.
Juliane WellerWellcome Sanger Institute, Hinxton, UK.
Thomas VandersticheleWellcome Sanger Institute, Hinxton, UK.
Uyen Linh HoCenter for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
Luca CrepaldiWellcome Sanger Institute, Hinxton, UK.
Jolanda van LeeuwenCenter for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
Felicity AllenWellcome Sanger Institute, Hinxton, UK.
Leopold PartsWellcome Sanger Institute, Hinxton, UK.

Funding

Biotechnology and Biological Sciences Research CouncilWellcome TrustWellcome Trust 206194
6 · The paper itself

Abstract

CRISPR/Cas base editors promise nucleotide-level control over DNA sequences, but the determinants of their activity remain incompletely understood. We measured base editing frequencies in two human cell lines for two cytosine and two adenine base editors at ∼14 000 target sequences and find that base editing activity is sequence-biased, with largest effects from nucleotides flanking the target base. Whether a base is edited depends strongly on the combination of its position in the target and the preceding base, acting to widen or narrow the effective editing window. The impact of features on editing rate depends on the position, with sequence bias efficacy mainly influencing bases away from the center of the window. We use these observations to train a machine learning model to predict editing activity per position, with accuracy ranging from 0.49 to 0.72 between editors, and with better generalization across datasets than existing tools. We demonstrate the usefulness of our model by predicting the efficacy of disease mutation correcting guides, and find that most of them suffer from more unwanted editing than pure outcomes. This work unravels the position-specificity of base editing biases and allows more efficient planning of editing campaigns in experimental and therapeutic contexts.

Indexed as

CRISPR-Cas SystemsGene EditingAdenineCytosineHumansNucleotidesAdenineCytosineNucleotides

Identifiers

PMID35286377
PMCPMC8989541

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.