Evidence map›Paper›PMID 34791389›Full record

ArticleNucleic acids research2022

Uncertainty-aware and interpretable evaluation of Cas9-gRNA and Cas12a-gRNA specificity for fully matched and partially mismatched targets with Deep Kernel Learning.

Bogdan Kirillov, Ekaterina Savitskaya, Maxim Panov, Aleksey Y Ogurtsov, Svetlana A Shabalina, Eugene V Koonin, Konstantin V Severinov

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 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. Deep learning in CRISPR-Cas systems: a review of recent studies.Frontiers in bioengineering and biotechnology · 2023
    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

7 authors.

Bogdan KirillovCenter for Life Sciences, Skolkovo Institute of Science and Technology, Moscow 143026, Russia.ORCID 0000-0002-7104-8613
Ekaterina SavitskayaCenter for Life Sciences, Skolkovo Institute of Science and Technology, Moscow 143026, Russia.
Maxim PanovCenter for Computational and Data-Intensive Science and Engineering, Skolkovo Institute of Science and Technology, Moscow 143026, Russia.
Aleksey Y OgurtsovNational Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.
Svetlana A ShabalinaNational Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.ORCID 0000-0002-3774-819X
Eugene V KooninNational Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.ORCID 0000-0003-3943-8299
Konstantin V SeverinovCenter for Life Sciences, Skolkovo Institute of Science and Technology, Moscow 143026, Russia.ORCID 0000-0001-9706-450X

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The choice of guide RNA (gRNA) for CRISPR-based gene targeting is an essential step in gene editing applications, but the prediction of gRNA specificity remains challenging. Lack of transparency and focus on point estimates of efficiency disregarding the information on possible error sources in the model limit the power of existing Deep Learning-based methods. To overcome these problems, we present a new approach, a hybrid of Capsule Networks and Gaussian Processes. Our method predicts the cleavage efficiency of a gRNA with a corresponding confidence interval, which allows the user to incorporate information regarding possible model errors into the experimental design. We provide the first utilization of uncertainty estimation in computational gRNA design, which is a critical step toward accurate decision-making for future CRISPR applications. The proposed solution demonstrates acceptable confidence intervals for most test sets and shows regression quality similar to existing models. We introduce a set of criteria for gRNA selection based on off-target cleavage efficiency and its variance and present a collection of pre-computed gRNAs for human chromosome 22. Using Neural Network Interpretation methods, we show that our model rediscovers an established biological factor underlying cleavage efficiency, the importance of the seed region in gRNA.

Indexed as

CRISPR-Cas SystemsDeep LearningGene EditingGene TargetingAlgorithmsGenomicsHumansNeural Networks, ComputerReproducibility of ResultsRNA, Guide, CRISPR-Cas SystemsRNA, Guide, CRISPR-Cas Systems

Identifiers

PMID34791389
PMCPMC8789050

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.