Evidence map›Paper›PMID 36068235›Full record

ArticleNature communications2022

Accounting for small variations in the tracrRNA sequence improves sgRNA activity predictions for CRISPR screening.

Peter C DeWeirdt, Abby V McGee, Fengyi Zheng, Ifunanya Nwolah, Mudra Hegde, John G Doench

Abstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing 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

35 citing papers in PubMed.

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  10. ViableFrontiers in immunology · 2026
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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

6 authors.

Peter C DeWeirdtGenetic Perturbation Platform, Broad Institute of MIT and Harvard, 75 Ames St, Cambridge, MA, USA.
Abby V McGeeGenetic Perturbation Platform, Broad Institute of MIT and Harvard, 75 Ames St, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-9294-7039
Fengyi ZhengGenetic Perturbation Platform, Broad Institute of MIT and Harvard, 75 Ames St, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-4479-604X
Ifunanya NwolahGenetic Perturbation Platform, Broad Institute of MIT and Harvard, 75 Ames St, Cambridge, MA, USA.
Mudra HegdeGenetic Perturbation Platform, Broad Institute of MIT and Harvard, 75 Ames St, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-4530-4633
John G DoenchGenetic Perturbation Platform, Broad Institute of MIT and Harvard, 75 Ames St, 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

CRISPR technology is a powerful tool for studying genome function. To aid in picking sgRNAs that have maximal efficacy against a target of interest from many possible options, several groups have developed models that predict sgRNA on-target activity. Although multiple tracrRNA variants are commonly used for screening, no existing models account for this feature when nominating sgRNAs. Here we develop an on-target model, Rule Set 3, that makes optimal predictions for multiple tracrRNA variants. We validate Rule Set 3 on a new dataset of sgRNAs tiling essential and non-essential genes, demonstrating substantial improvement over prior prediction models. By analyzing the differences in sgRNA activity between tracrRNA variants, we show that Pol III transcription termination is a strong determinant of sgRNA activity. We expect these results to improve the performance of CRISPR screening and inform future research on tracrRNA engineering and sgRNA modeling.

Indexed as

Clustered Regularly Interspaced Short Palindromic RepeatsRNA, Small UntranslatedCRISPR-Cas SystemsGenomeTranscription, GeneticRNA, Small Untranslated

Identifiers

PMID36068235
PMCPMC9448816

What OpenQuestion holds

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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.