Evidence map›Paper›PMID 30808944›Full record

ArticleScientific reports2019

Unlocking HDR-mediated nucleotide editing by identifying high-efficiency target sites using machine learning.

Aidan R O'Brien, Laurence O W Wilson, Gaetan Burgio, Denis C Bauer

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed, 1 pooled it
2.2field-weighted citation impact, top 11% 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

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

  1. CRISPR for cystic fibrosis: Advances and insights from a systematic review.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Pooled it
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  8. Beyond a few bases: methods for large DNA insertion and gene targeting in plants.The Plant journal : for cell and molecular biology · 2025
    Review
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  13. Review
  14. Article
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  16. Article
  17. CRISPR genome surgery in a novel humanized model for autosomal dominant retinitis pigmentosa.Molecular therapy : the journal of the American Society of Gene Therapy · 2022
    Article
  18. Article
  19. Challenges of CRISPR-Based Gene Editing in Primary T Cells.International journal of molecular sciences · 2022
    Review
  20. 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

4 authors at 2 institutions in 1 country.

Aidan R O'BrienCSIRO, Sydney, NSW, Australia.
Laurence O W WilsonCSIRO, Sydney, NSW, Australia.
Gaetan BurgioJohn Curtin School of Medical Research, Australian National University, Canberra, ACT, Australia. gaetan.burgio@anu.edu.au.ORCID 0000-0002-7434-926X
Denis C BauerCSIRO, Sydney, NSW, Australia. Denis.Bauer@csiro.au.
Commonwealth Scientific and Industrial Research Organisation · AUAustralian National University · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Editing individual nucleotides is a crucial component for validating genomic disease association. It is currently hampered by CRISPR-Cas-mediated "base editing" being limited to certain nucleotide changes, and only achievable within a small window around CRISPR-Cas target sites. The more versatile alternative, HDR (homology directed repair), has a 3-fold lower efficiency with known optimization factors being largely immutable in experiments. Here, we investigated the variable efficiency-governing factors on a novel mouse dataset using machine learning. We found the sequence composition of the single-stranded oligodeoxynucleotide (ssODN), i.e. the repair template, to be a governing factor. Furthermore, different regions of the ssODN have variable influence, which reflects the underlying mechanism of the repair process. Our model improves HDR efficiency by 83% compared to traditionally chosen targets. Using our findings, we developed CUNE (Computational Universal Nucleotide Editor), which enables users to identify and design the optimal targeting strategy using traditional base editing or - for-the-first-time - HDR-mediated nucleotide changes.

Indexed as

DNA RepairGene EditingMachine LearningAnimalsCRISPR-Cas SystemsDNA Breaks, Double-StrandedMiceMice, Inbred C57BLMutationOligodeoxyribonucleotidesRNA, Guide, CRISPR-Cas SystemsOligodeoxyribonucleotidesRNA, Guide, CRISPR-Cas Systems

Identifiers

PMID30808944
PMCPMC6391469
OpenAlexW2953226042

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.