Evidence map›Paper›PMID 37400521›Full record

ArticleNature biotechnology2024

Prediction of on-target and off-target activity of CRISPR-Cas13d guide RNAs using deep learning.

Hans-Hermann Wessels, Andrew Stirn, Alejandro Méndez-Mancilla, Eric J Kim, Sydney K Hart, David A Knowles, Neville E Sanjana

Abstract read
PubMed Publisher
In one paragraph

Article in Nature biotechnology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.

0numbers the graph read from it
0cells of the map it votes in
75citing papers in PubMed
16.9field-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

75 citing papers in PubMed, 110 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. Machine Learning for CRISPR-Based Diagnostics.International journal of molecular sciences · 2026
    Review
  11. Review
  12. Review
  13. Article
  14. Article
  15. A foundation model for nucleotide sequences.Nucleic acids research · 2026
    Article
  16. Review
  17. Review
  18. Review
  19. Article
  20. Article

15 more citing papers are in PubMed but not listed here.

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 at 3 institutions in 1 country.

Hans-Hermann Wessels *New York Genome Center, New York City, NY, USA.ORCID http://orcid.org/0000-0001-5551-404X
Andrew Stirn *New York Genome Center, New York City, NY, USA.
Alejandro Méndez-MancillaNew York Genome Center, New York City, NY, USA.ORCID http://orcid.org/0000-0002-2776-9229
Eric J KimDepartment of Computer Science, Columbia University, New York City, NY, USA.
Sydney K HartNew York Genome Center, New York City, NY, USA.ORCID http://orcid.org/0000-0003-0228-6471
David A KnowlesNew York Genome Center, New York City, NY, USA. daknowles@nygenome.org.ORCID http://orcid.org/0000-0002-7408-146X
Neville E SanjanaNew York Genome Center, New York City, NY, USA. nsanjana@nygenome.org.ORCID http://orcid.org/0000-0002-1504-0027
New York Genome Center · USCity University of New York · USColumbia University · US

Funding

In situ functional genomics to understand transcriptional regulationDP2HG010099 · NHGRI · NEW YORK GENOME CENTER · PI SANJANA, NEVILLE · 2017 to 2022
$4.4M
U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI) DP2HG010099
6 · The paper itself

Abstract

Transcriptome engineering applications in living cells with RNA-targeting CRISPR effectors depend on accurate prediction of on-target activity and off-target avoidance. Here we design and test ~200,000 RfxCas13d guide RNAs targeting essential genes in human cells with systematically designed mismatches and insertions and deletions (indels). We find that mismatches and indels have a position- and context-dependent impact on Cas13d activity, and mismatches that result in G-U wobble pairings are better tolerated than other single-base mismatches. Using this large-scale dataset, we train a convolutional neural network that we term targeted inhibition of gene expression via gRNA design (TIGER) to predict efficacy from guide sequence and context. TIGER outperforms the existing models at predicting on-target and off-target activity on our dataset and published datasets. We show that TIGER scoring combined with specific mismatches yields the first general framework to modulate transcript expression, enabling the use of RNA-targeting CRISPRs to precisely control gene dosage.

Indexed as

Deep LearningRNA, Guide, CRISPR-Cas SystemsClustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Cas SystemsGene EditingHumansRNARNARNA, Guide, CRISPR-Cas Systems

Identifiers

PMID37400521
OpenAlexW4382989753

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.